Most of the Roskamp Institute’s funding comes from grant funding and the general public — people like you. Your gift makes a difference in the lives of people facing diseases such as Alzheimer’s Disease, Head Trauma, Drug Addiction, Cancer and Tourette’s Syndrome. Your contribution to the not-for-profit (501[c]3) Roskamp Institute is tax deductible and supports research to improve treatment and to ultimately develop a cure for these devastating diseases.

If you contribute to the Roskamp Institute by participating in the 36-Hour Giving Challenge at Giving Partner Challenge anytime between March 27 at 6 am and March 28 at 6 pm, your donation stands a great chance of being matched penny for penny.

Help us get a special grant for attracting the most donors. (We can win up to $20,000 by having the most unique donors give $25 or more to us.) Help us earn one of 20 grants for being among the first nonprofits to have 50 donors donate $50 or more.One random donor per hour will receive an additional $250 added to his/her donation. That could be you!You can help us get one of two $5,000 grants by visiting our profile on www.thegivingpartner.org during the challenge.

The Roskamp Foundation, a private foundation established by Bob and Diane Roskamp to administer all their philanthropic work in Sarasota and throughout the country. The Foundation has pledged to match all gifts to the Institute dollar for dollar that come in during the 36-Hour Giving Challenge, up to a maximum total of $50,000.

The money raised through the Giving Challenge will be used to further our research and will make a significant difference in the lives of people facing diseases such as Alzheimer’s Disease, head trauma, Gulf War Syndrome, Autism, drug addiction and Tourette’s Syndrome.

All donations must be made online. When you are ready to make your donation on March 27, go to www.GivingPartnerChallege.org, enter Roskamp in the box at the upper right where it says “Search for Organizations” and then click Search. You will then go to a page with the Institute’s information which you will click on and the donation form will appear.

However, you can make your pledge right now and you won’t have to get up at 6:00 a.m. Just click below:

http://www.rfdn.org/donate36hrs.html

to DONATE NOW! and we’ll process your donation for you between March 27, 6 a.m. and March 28, 6 p.m.

Thank you for your gift to the Roskamp Institute to help us continue our very important work. If you have any questions or if you would like to make your donation right now over the phone, please call me directly at 941-752-2949 extension 390.

To learn more about supporting Roskamp Institute, please contact:

Mr. Steve Klindt
Director of Development
Roskamp Institute

2040 Whitfield Avenue,
Sarasota, FL 34243

Phone: 941-752-2949 ext 390
Fax: 941-752-2948

Email: Steve Klindt

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

For more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

Please see full press release at: Star Scientifi

The Roskamp Institute is a stand-alone, not-for-profit research facility located in Sarasota, Florida headed by Drs. Mike Mullan and Fiona Crawford.

http://news.yahoo.com/nicotine-may-help-combat-memory-loss-215902174.html#ugccmt-post-frm-container

http://www.michaelmullan.us

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

The patient has never met Michael Mullan, nor Fiona Crawford. But some 4,150 miles away, they could hardly be happier about his test results.

They show that the man, whose identity is confidential, is showing no adverse reactions to a drug that might be a promising treatment for Alzheimer’s disease.

That is good news for Mullan and Crawford. Directors of the Roskamp Institute, on Whitfield Avenue in southern Manatee County, they are running a clinical trial of Nilvadipine, a drug widely used abroad but not approved in the United States.

The drug is intended to lower blood pressure. But in studies on mice, Roskamp researchers found it also reduced the level of a protein in the brain believed to be at the heart of Alzheimer’s.

The Ireland trial just completed its second phase, a safety study, and the 20 patients taking the drug showed almost no ill effects, paving the way for a broader study.

The clinical trial is the institute’s highest-profile project, but its two dozen scientists also work in fields including drug addiction and head injury.

With even more promising treatments deep in its labs, the little nonprofit academic center is becoming more and more a biotechnology start-up.

Birth of the institute

The institute was born in 1997, but its origins date back another 40 years.

Bob Roskamp was a high school physics teacher. His older brother, diagnosed with schizophrenia, killed himself.

Roskamp tells the story with understatement: “Obviously, it catches your attention in a big way.”

The loss of his brother prompted him to give up teaching and work on opening homes for developmentally disabled adults. He later moved into developing housing communities for seniors.

He began selling his companies — including his Freedom Group to American Retirement Group for $23 million in cash and $14.9 million in stock — leaving him with a question: “What do we do with these surplus dollars?”

The answer is in the logo of the institute bearing his name: “Curing Diseases of the Mind.”

Roskamp and his wife, Diane, are among the pioneers of a style of philanthropy, now more widely followed, of carefully aiming resources at one target and tracking performance.

“Instead of spreading it thinly throughout the world, we would ‘rifle-shot’ it, and have a lot more fun with it,” he said.

Roskamp historically has given the institute about one-third of its operating budget, the rest coming through grants and contracts.

But as federal money has been diverted elsewhere, and the institute’s work has grown more complex, Roskamp has had to pick up more of the tab. He gave just over $1 million in 2005, but $4.6 million this year, he said.

His involvement began with funding a lab at the University of South Florida, then a teaching position eventually filled by Mullan.

In 2003, the institute left the university amid personnel and bureaucratic disputes and moved into the former Bausch & Lomb building in southern Manatee County. Roskamp said university overhead was too expensive, and that scientists can work faster in the independent setting.

“You bring your entrepreneurial hat to this kind of research,” he said. “We’re results-oriented people.”

The scientists appreciate not having to wait for grants and approvals.

“We have the funding from Bob and Diane that allow us to move forward very quickly when we make a new discovery,” Crawford said. “We are really free to focus on the research.”

Paddling mice

Most Alzheimer’s researchers now focus on a protein known as beta-amyloid that forms when a chemical process goes awry. The protein clumps together outside neurons, eventually killing those memory cells.

Mullan and Crawford were part of a team that in 1991 published papers establishing a link between a human gene, on chromosome 21, and early onset of the disease in patients in their 40s and 50s.

A year later, after they came to the United States, they published a paper looking at another genetic link to early-onset Alzheimer’s.

The research made beta-amyloid a prime suspect in Alzheimer’s, and stopping its buildup a potential cure.

Roskamp researchers look for existing drugs and new compounds with that effect. Nilvadipine showed enough promise to test it on lab mice engineered to have Alzheimer’s.

At 10 months, with the disease in full bloom, some mice got the drug while others got a placebo. Later, they scanned the mice’s brains for blood flow.

In the color-coded pictures, the brighter the image, the better the blood flow. The mice getting Nilvadipine scan largely red and orange.

The control animals scan mostly blue-green.

Mullan points to a chart with results of a more traditional test, tracking a mouse’s effort to paddle its way out of a mouse-sized swimming pool.

The mice repeat the test, day after day. Normal mice figure it out and eventually swim a shorter route to the exit.

Mice with Alzheimer’s disease never figure it out, actually taking longer and longer routes.

“But if you give them Nivaldipine, they go from here to here; they do better,” Mullan said, pointing at the figures. “And if you give Nilvadipine to a normal mouse, they do best of all.”

The drug appears to slow or stop the production of beta-amyloid, Mullan said.

As the brain grudgingly yields the mysteries of its architecture, Roskamp’s scientists are exploring how those diseases of the mind may be related by more than just words.

‘Blocking that burst’

In 2002 the institute teamed with the Department of Veterans Affairs to look at memory skills in people who had received traumatic brain injuries.

They found that people who had a gene linked to Alzheimer’s disease recovered less memory function than those without it, even when they had comparable injuries and demographics.

Further research has shown that when the brain suffers such an injury, there is a burst of amyloid production. One theory is that the brain produces the protein as a defense mechanism, but it sometimes overreacts and makes matters worse.

“Blocking that burst appears to be at least one way to try and improve outcomes after head injury,” said Crawford, lead author of the 2002 article.

Last year the Department of Defense approved a $1.5 million grant to the institute to expand that research. It is a particularly urgent matter for the military: Improved body armor is helping soldiers survive explosions — but with little-understood head injuries.

“People can have brain injury even if they didn’t suffer any loss of consciousness, weeks and months of being in the vicinity of an explosive attack,” Crawford said.

For now, that grant is hung up in final reviews.

“We have yet to see dime one,” Roskamp said — but even that $1.5 million pales in comparison with the costs of the Nilvadipine study.

That cuts to the heart of the dilemma scientists face. They might get a moderately effective drug to market quickly, or try to discover the “silver bullet,” which could take many years and exponentially more money.

Roskamp is preparing the foundation to do both.

Just a question of when

To Mullan, the question is not whether there will be treatments for Alzheimer’s.

“It’s the question of when we’re going to get them there,” he said.

It is a question of how effective they will be. Mullan cited three drugs far along in the pipeline, all targeted at reducing amyloid. “They’re not going to be block-busting, perfect drugs by any means, but I think at least two of them will be approved for Alzheimer’s this year.”

Nilvadipine most likely would be like them — useful but not the cure-all. But it offers some advantages.

Developing a new drug from scratch is a much worse bet, Mullan said. Count on 10 to 12 years for development, testing and approvals, with a high failure rate.

“Sometimes they fail spectacularly,” he said, citing Vioxx, a promising drug with unforeseen and deadly side effects.

Nilvadipine, in use for more than a decade, already has a track record for safety. It could help patients while allowing the institute time to find the silver bullet.

By mid-year, the institute hopes to continue the Ireland trial with a double-blind study, meaning neither patients nor doctors know who gets Nilvadipine and who gets a placebo until they conclude. That study, which would involve about 200 people, could cost $20 million, Roskamp said.

Should the drug prove effective, Nilvadipine’s manufacturer could profit — but so would the institute. Because it holds rights to the drug’s newly indicated use, the institute would receive royalty payments, Roskamp said.

The institute has set up a for-profit subsidiary, Roskamp Research LLC, which holds its patents. Roskamp structured it to allow outside backers to support studies, provide the subsidiary with a return on its investment, and guarantee most of the revenue goes to his institute.

“We don’t want to give it to a pharma company, and say here, go make a lot of money off of it,” Roskamp said.

Compounds back in the institute’s labs could provide better returns — and better treatments.

While the Roskamp Institute’s primary focus is on Alzheimer’s disease, Roskamp researchers have a significant interest in diabetes due to studies that suggest those who have diabetes are more likely to develop Alzheimer’s disease.

The study found that a deficiency in an enzyme, atypical protein kinase C, impairs the ability of insulin to stimulate glucose uptake into the muscle, which produces a state of resistance to circulating insulin.  Once this occurs, the liver begins to produce excessive quantities of fat, causing abdominal obesity and alterations in blood lipids.  According to the study, this can then lead to obesity and the metabolic syndrome, the precursors of type 2 diabetes.

“Although this gene-knockout study was done on mice, it is particularly relevant to type 2 diabetic humans, who are known to have deficiencies of this enzyme in their muscles,” said Dr. Farese.  “The findings showed that in the mice a simple loss of one or more genes that are responsible for the production of this enzyme could eventually cause obesity and the metabolic syndrome which then could lead to type 2 diabetes.”

Further research must be done to determine how human diabetics acquire a deficiency of this enzyme in their muscles; however, this mouse model should be especially helpful to further study and devise treatments for obesity and the metabolic syndrome.

“We are particularly excited about this study and the potential to develop treatments for obesity and the metabolic syndrome, which are both global health problems,” said Dr. Michael Mullan, director of the Roskamp Institute.  “This study will also be helpful in further determining how obesity, the metabolic syndrome and type 2 diabetes are linked to Alzheimer’s disease.”

The study was co-authored by Dr. Farese, who led the team of Mini P. Sajan, Hong Yang, and Sonali Nimal at the Roskamp Institute; and others at the James A. Haley Veterans Administration Medical Center in Tampa; the University of South Florida College of Medicine; the Joslin Research Foundation and Harvard University School of Medicine; Yale University School of Medicine, and Research Center at Oslo, Norway.

For more information regarding this study or the Roskamp Institute please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

Researchers at the Roskamp Institute also showed that the presence of functional CD40/CD40L signaling is essential for the full development of AD like pathology in transgenic mouse models of AD. In particular, it was demonstrated that accumulation of cerebral Ab is reduced in transgenic mouse models of AD by genetically or pharmacologically reducing the availability of CD40L to CD40. The Roskamp Institute investigators subsequently revealed that loss of functional CD40L diminishes both APP processing to Ab and microglial activation in the brain (Original findings published in journals Science and Nature Neuroscience). CD40L activated pathways in the presence of Ab appear to mediate both of these effects as well as the hyperphosphorylation of murine tau in vivo at epitopes analogous to those which precede tangle formation of human tau. More recently, Dr. Ghania Ait-Ghezala of the Roskamp Institute showed that CD40/CD40L interaction also affects APP via the NF-kB pathway. Using NF-kB inhibitors and SiRNAs to silence diverse elements of the NF-kB pathway, she demonstrated that reduction in levels of both pathological forms of Ab. These results showed that CD40L stimulation may be a key component in AD pathology and that NF-kB pathway may be suitable targets for therapeutic approaches against AD.

Another major focus of research at the Roskamp Institute includes Traumatic Brain Injury (TBI) Program headed by the Associate Director of the Roskamp Institute. Dr. Crawford and her Roskamp Institute team demonstrated an important relationship between apolipoprotein E (APOE) and memory following TBI. She demonstrated that in Veteran’s with TBI, memory performance was significantly worse in individuals who had at least one copy of APOE ε4 allele than those who did not. She had subsequently been funded through the Veteran’s Administration to further study the relationship between different forms of APOE in TBI with the emphasis on finding treatments for this devastating condition.

Drs. Michael Mullan and Fiona Crawford also received funding by the Counterdrug Technology Assessment Center (CTAC) to evaluate the newly emerged genomics and proteomics technology and find biological markers of substance abuse. Recently, Dr. Crawford’s team showed that cocaine treatment of human progenitor neuronal cells results in increased oxidative stress (possibly mediated by inflammatory responses) which precedes cell death. Thus, these findings may have implications for the consequences of cocaine abuse in situations where antioxidant capacity is compromised, as in the aging brain.

As evident here, the Roskamp Institute team has been a pioneer in many area of research in neuropsychiatric diseases and will continue to do so to find novel therapies for these disorders. Currently, a new clinical trial based on the discoveries made at the Roskamp Institute is underway to assess safety and efficacy of nilvadipine in treatment of Alzheimer’s disease. Through the generous support of Diane and Robert Roskamp, the Veteran’s Administration, the National Institutes of Health, CTAC and the Department of Defense, the Roskamp Institute will continue to provide potential avenues for novel therapeutic interventions for neuropsychiatric disorders.

for more information on the Roskamp Institute please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

for more information on the Roskamp Institute please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

The Roskamp Institute scientists have previously shown that a genetic change called polymorphism in a gene for an opioid receptor in the brain is a risk factor for alcohol dependency. With this information, the Roskamp Institute researchers then examined the frequencies of this polymorphism carrying genotypes and alleles in numerous groups of individuals addicted to the substance versus individuals with no history of addiction to the substance. These Roskamp Institute scientists found that the mu-opioid receptor’s polymorphism is a genetic risk factor for substance dependence but not to any particular type of drug. Meaning, an individual with this polymorphism is more likely to become addicted to a substance than an individual without it. The Roskamp Institute previously published these findings in the journal Molecular Psychiatry.

Dr. Mullan and Dr. Crawford along with the other researchers at the Roskamp Institute received an award from the Counter drug Technology Assessment Center (CTAC), to continue their work on drug addiction.

Affymetrix is a name of the company which provides the Roskamp Institute with the genetic software that is used by scientists who study genetics (genomics). The Roskamp Institute used genomics technology in order to find the cocaine’s affects on the brain cells known as neuronal cells.  The Roskamp Institute scientists continue to research projects which are focused on the inflammatory and immune responses to cocaine.  The Roskamp Institute scientists showed that these responses also results from the exposure of the neuronal cells to cocaine and these responses are also time dependant. These findings, originally published in the Journal of Neurochemistry, illustrate that there are biological and physical consequences of cocaine addiction.

The Roskamp Institute researchers are currently working on studies involving oxidative stress in the brain.  This oxidative stress can also be caused by excessive use of cocaine and is hypothesized to result in permanent brain damage.  With such experiments in progress, the Roskamp Institute is a good candidate for additional government funding and  these discoveries will be useful towards the battle against drug abuse in form of treatments.

Most individuals with a mild traumatic brain injury improve entirely within a year,but moderate and severe brain injuries are more complex and have long-term consequences. The Center of disease Control and Prevention estimated that 5.3 million Americans are living with disabilities resulting from traumatic brain injury. Dr. Michael Mullan (Director of the Roskamp Institute) Dr. Fiona Crawford (Associate Director of the Roskamp Institute) and their team of scientists previously demonstrated that apolipoprotein E (APOE) influences traumatic brain injury outcomes. These Roskamp Institute scientists examined 110 participants from the Defense and Veterans’ Head Injury Program to determine a relationship between APOE genotype and memory performance on certain cognitive tests administered to these head injured soldiers. The memory performance was much worse in soldiers who had at least had one APOE epsilon 4 allele compared to those who did not. This Roskamp Institute team also determined that these findings were limited to memory and not other cognitive performances such as executive functioning. Therefore, these data support a specific role for the APOE protein in memory outcome following TBI, and suggest an APOE isoform-specific effect on neuronal repair processes (originally published in the journal Neurology).

Dr. Fiona Crawford received a Merit award from the Veteran’s Administration to further study, using genomics technology, the role of APOE in Traumatic Brain Injury. Dr. Fiona Crawford and her Roskamp Institute team have now completed the experiments showing differences in genomics response among the different mouse models after traumatic brain injury.  Recently, Drs. Michael Mullan and Fiona Crawford received a prestigious award of $1.5 million from the Department of Defense which will allow the Roskamp Institute to investigate ApoE and other proteins to find potential peripheral biological markers and novel therapeutic treatments for traumatic brain injury. Florida Senator Bill Nelson recently toured the Roskamp Institute to observe its traumatic brain injury program in support of the soldiers affected by this devastating condition.

The Roskamp Institute is a world-renowned state-of-the-art research and clinical facility located in Sarasota Florida dedicating to finding novel therapeutics for treatment of neuropsychiatric disorder, especially Alzheimer’s disease, traumatic brain injury and substance abuse. The Roskamp Institute is supported by the funding from government agencies such the National Institutes of Health, the Veteran’s Administration and the Department of Defense as well as private donations from the Robert and Diane Roskamp Foundation.

for more information on Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

The Roskamp Institute scientists Drs. Michael Mullan (Director of the Roskamp Institute), Fiona Crawford (Associate Director of the Roskamp Institute) and Ghania Ait-ghezala (a senior scientist at the Roskamp Institute) have previously shown that among patients diagnosed with Tourettes syndrome in two unrelated families, there appears to be a breakage and translocation on chromosome 8 (original findings published in the journal Human Genetics).  Drs. Fiona Crawford and Ghania Ait-ghezala subsequently received funding from the Tourettes syndrome association to further characterize this chromosomal breakage.

Currently, there is no treatment available for Tourettes syndrome. Although, the symptoms in most individuals improve by the late teens and early 20s, this disorder is generally lifelong and chronic.  Studies have also shown that although symptoms such as tics may disappear after the childhood period, it is possible that other psychiatric disorders such as depression, panic attacks, mood swings, and antisocial behaviors persist and cause lifelong impairment in adults.  Therefore, a treatment for this disorder is much needed so that a child can actually be disease free throughout his/her life and has a decent chance of living a normal life. The Roskamp Institute is currently engaged in molecular biological research aimed at determining the genes that are disturbed when this chromosomal breakage and translocation occur. Through this novel finding, the scientists at the Roskamp Institute hope to discover a treatment for Tourettes syndrome.

The Roskamp Institute is located in Sarasota Florida and is a not-for-profit stand alone research institute dedicated to finding cures for neuropsychiatric disorders. The Roskamp Institute is currently conducting a clinical trial evaluating safely and efficacy of nilvadipine for the treatment for Alzheimer’s disease (clinical trial being performed in Dublin, Ireland). Furthermore, the Roskamp Institute is conducting various molecular biological studies to find treatment for chronic diseases such as cancer, diabetes, and other neuropsychiatric disorders such as traumatic brain injury, gulf war syndrome, and substance abuse. The Roskamp Institute operates two memory disorder clinics located in Sarasota and Tampa, Florida. These clinics conduct diagnostic assessments for memory disorders and conduct industry and government funded clinical trials in several neurological and neuropsychiatric disorders. The Roskamp institute is currently funded by the National Institutes of Health, the Veteran’s Administration, the Department of Defense and the private donation by the Robert and Diane Roskamp foundation. For more information or the research or clinical trials, please contact us at 94-752-2949.

Sarasota, Fla. – The Roskamp Institute today welcomed U.S. Senator Bill Nelson to its research facility in Sarasota, Florida, where the Senator toured the laboratories and discussed the various types of research currently being conducted at the Institute.

“We thank Senator Nelson for his interest in our research and for coming to the Institute to tour our lab and view our good work first hand,” said Dr. Michael Mullan, director of the Roskamp Institute.  “We are proud of the research our Institute has done and look forward to continuing in our quest to better understand and ultimately cure debilitating diseases of the mind.”

While Senator Nelson’s visit was mainly to discuss with the researchers the current and future research being done in relations to Traumatic Brain Injury, the Roskamp Institute is devoted to understanding the causes of and finding cures for various neuropsychiatric and neurodegenerative disorders and addictions.  Specifically, the Institute utilizes a broad range of scientific approaches to understand the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease.

“We currently have 45 scientists and 10 clinicians with eight active clinical trials in the field with several more on the horizon,” Dr. Mullan continued.  “It is vital that we are persistent in our pursuit to help Florida’s sufferers and their families and we are glad Senator Nelson is here to share in our goal.”

The Roskamp Institute has built its esteemed reputation amongst the research community and has been heralded for its achievements including:

• Being the first Florida-based Alzheimer’s Research Institute (and one of only a handful of Institutes worldwide) to conduct a human clinical trial with a drug discovered by its own research.
• Discovering a new class of drugs that lower the production of the main pathological protein that causes Alzheimer’s disease.
• Applying state of the art technologies (proteomics and genomics) to find early diagnostic markers for Alzheimer’s disease.

Extensive participation from Florida residents in the Institute’s leading edge Alzheimer’s research program.

for more information on Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

Dr. Michael Mullan is an accredited professional from biomedical field. He has extensively researched on the causes and prospective cures of Alzheimer’s disease and other neurodegenerative disorders conditions. Based in Sarasota, Florida, he is reputed Director of Roskamp Institute. He is a highly qualified professional and has dedicated his time to finding cures for neuropsychiatric and neurodegenerative disorders and addictions. Dr. Mullan’s Alzheimer research work has provided invaluable insights on the disease with which many potential cures have been developed and tested. Dr. Mullan’s Alzheimer research indicates that one of the causes directly related to the disease is the excess accumulation of beta-amyloid, a type of protein, present in the brain. It was estimated that the protein is produced in every human but its excess accumulation can result in Alzheimer’s. Besides, Dr. Mullan’s Alzheimer research continuously tests medications and therapeutic treatments to help slow down the accumulation of beta-amyloid and related inflammation in patients.

About Dr Michael Mullan

Dr Michael Mullan has been working in the biomedical field for many years. He is a leading researcher with special expertise in assessment of the earliest cognitive symptoms and stages of Alzheimer’s disease. Mullan’s Alzheimer research works are also published in various articles which help students and researchers for making new discoveries. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Dr. Michael Mullan is the Director of the Roskamp Institute, and along with his team, he discovered the concept of ‘Swedish mutation’, a genetic error which results in overproduction of beta-amyloid by aberrant proteolytic processing of amyloid precursor protein (APP).  The concept of Swedish mutation now forms the bases of most mouse model of Alzheimer’s disease. Many tests and findings by the Roskamp Institute resulted in several therapeutic prospects for the treatment of Alzheimer’s disease as well as Cancer.

The Roskamp Institute has contributed greatly by providing research on the treatments of several neuropsychiatric disorders like traumatic brain injury, substance abuse, and Alzheimer, etc. With the guidance and knowledge provided by Dr. Mullan, the institute tested many causes and correlations between Alzheimer’s disease and proteins present in human brain. With Dr. Mullan’s Alzheimer research, several types of genetic variations, which can be the cause of Alzheimer’s, have been identified. It was discovered that the central reason to the disease process is a small protein identified as the ß (beta)-amyloid. Although, this protein is present normally in the human brain, but at times excess or abnormal accumulation can result in Alzheimer’s disease. With Dr. Mullan’s Alzheimer research, the institute tests cutting edge cures, therapeutic treatments and medications to slow down the process of toxic ß-amyloid accumulation.

Dr Mullan’s Alzheimer research proves that Aβ peptide prevents blood vessel growth and eventually inhibits tumor growth in brain. To identify if Aβ has the same effect with short derivatives, he studied various sequences within the Alzheimer’s Aβ peptide which have potential therapeutic relevance in preventing tumor growth. Dr. Mullan’s Alzheimer research work has contributed exceptionally to the field to help understand the disease and find its cures. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Early onset Alzheimer’s disease.

The term “early onset Alzheimer’s” is frequently misunderstood or used in a confusing way.  What we generally mean by  early onset Alzheimer’s is Alzheimer’s that onsets before the age to 60 years.  This is in contrast to the term early onset as referencing the early stage of the disease.  This is a confusing way to use the term and is discouraged.  Early stage disease is a better term to describe the early phases of the disease. Early onset familial disease occurs in families that are affected in multiple generations by mutations in genes that can trigger the disease.  Families of early onset disease thankfully are very rare but they have provided great insight into the disease process probably in all cases of the disease (early and late onset).  Sadly, frequently in these families the disease is inherited in what is known as an autosomal dominant fashion.  Autosomal dominant inheritance means that 50% of the offspring of each generation on average are impacted by the disease.  Some generations may be very fortunate and although they may be at risk for inheriting the diseased gene from one or the other parent none of the siblings in a sibship may be affected.  On the contrary sibships can be very unlucky in which case more than 50% are impacted with the disease.  For each child of an affected parent there is a 50% chance of inheriting the disease and this chance is not influenced by whether other siblings have already inherited the disease or not.

Unfortunately the inheritance of these rare genetic variance means that individuals at risk are highly likely to develop the disease if they live long enough.  One of the important characteristics of these familial mutations is that the disease tends to onset around approximately the same time of life.  Thus if a family has a mean (average) age of onset of 52 and one inherits one of these rare generic  errors then one is unlikely to live to 60 without developing  signs or symptoms of the disease.  By contrast if one does not carry the mutation then there is no more risk for the disease than the general population.

Again it is most important to emphasize that such families are extremely rare and early onset Alzheimer’s is not the most likely reason for patients or their families to visit the Roskamp Institute Clinic.  In fact, approximately 1% or less of cases of Alzheimer’s Disease have what can be described as early onset disease.  In the past, individuals who come from such families have sought genetic counseling including genetic testing for these genetic errors.  It is relatively straightforward to detect such errors but clearly the genetic information is highly sensitive.  Family members should therefore think very carefully before seeking such information however initially finding out more about early onset disease is a recommended step.

Clinicians at the Roskamp Institute are happy to discuss early onset disease with patients and their families as they wish.  Finally it should be noted that many cases of early onset disease occur without a family history.  Thus individuals can manifest the disease before the age of 60 but have no other known family members either in the prior generations or in subsequent generations that develop the disease the cause of early onset Alzheimer’s that is not familial is not well understood but importantly there is no risk to subsequent family members for development of the disease.

Late onset (common) Alzheimer’s disease.  Much more commonly patients and their families come to the clinic at the Roskamp Institute and seek advice on the inheritance of Alzheimer’s when one or more members of the family has late onset disease.  This is defined as disease which onsets over the age of 60 and this is by far in a way the most common cause of the disease. It is estimated that approximately 4 million Americans presently either have the disease or are in the early or pre clinical stages – most of these cases are late onset Alzheimer’s Disease.  The predicted numbers for future disease prevalence are very high. For instance it is estimated that by mid century there could be as many as two hundred million individuals afflicted with the disease.

Most late onset Alzheimer’s disease does not exhibit a clear autosomal dominant pattern meaning that the risk to offspring of individuals suffering with the disease is usually considerably less than 50%.  Certain genetic risk factors for late onset disease have been identified – the most important of which is apolipoprotein E (APOE).  There are 3 common forms of APOE: E2, E3 and E4.  The discovery by Allen Roses and his colleagues at Duke University showed that Alzheimer’s disease sufferers were much more likely to carry one or two copies of the E4 allele (genetic form) of APOE than the normal population.  Carrying one copy of APOE 4 increases ones risk for the disease by approximately three times and carrying two copies can increase the risk for the disease by up to fifteen times compared to individuals who do not carry an APOE 4 allele.

Many family members express interest in being genetically tested for their risk for the disease.  Such tests are commercially available but most centers discourage the use of testing prior to symptoms because many individuals who carry an APOE 4 allele do not necessarily develop the disease at least until late old age.  Conversely it’s very possible to develop Alzheimer’s disease without carrying an APOE 4 allele. Therefore on an individual basis the test is not overly helpful in specifying who may or may not develop the disease.  However on a group basis APOE genetic testing is very helpful to give an average estimate of the numbers of individuals who will subsequently develop Alzheimer’s.

It is anticipated that as better treatments are available for Alzheimer’s disease there will be greater interest in genetic testing.  For instance it is expected that as treatments are used earlier and earlier in the stages of the disease that individuals in the very early stage or maybe with no symptoms at all might seek medical treatment once such treatment has been established as effective in stopping the rate of progression or disease onset.

Despite the fact that genetic testing is not used frequently in clinical practice it is a tremendous tool in assisting researchers in understanding when and why the diseases develops and in planning clinical trials to take into account who is most likely to develop the disease.  Already there is evidence from several clinical trials that individuals that carry the APOE 4 allele may be more refractory to certain treatments.  As drug development progresses it will be important to develop medications that are able to tackle the severest form of the disease i.e. those patients who are carrying and APOE 4 allele.

Summary:   The two types of familial Alzheimer’s disease differ in the risk for offspring of developing the disease.  The early onset cases as noted have children that are highly at risk for developing the disease if there is a family history.  By contrast late onset disease or low clustering in families is much less genetically predisposed.  In both cases genetic tests are available but are generally discouraged particularly for late onset disease.  Roskamp Institute researchers and clinicians are well versed in the genetic aspects of the disease and can advise on an individual or family basis as required.

The Roskamp Institute is a not-for-profit research Institute located in Sarasota and Tampa, Florida, that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders and addictions with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinics also offer comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

By Dr. Michael Mullan, Director of Alzheimer Research Institute, The Roskamp Institute

for more information on Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

Providing hope for patients and their families is a critical part of interfacing with them.  In addition helping families to come to terms with a disorder  that can impact many aspects of  their love ones’ lives (including social interactions, pastimes and sports, financial transactions and medical legal issues) enables families to make the necessary adjustments  to deal with the condition.  Naturally a particularly satisfying interaction can occur when certain elements of a patient’s health can be altered to improve the outcome once a diagnosis of Alzheimer’s has been made.  For instance we know that cardio-vascular health interacts critically with Alzheimer’s disease and aversion of cerebrovascular events (such as small strokes or transient ischemic attacks) has a highly beneficial effect on the outcome of Alzheimer’s patients.  In addition other conditions such as diabetes or thyroid disease can interact negatively with the disease.  These and many other treatable causes of cognitive dysfunction appear at the Roskamp Memory Clinic and are regularly amenable to intervention.  Sometimes previous diagnoses are found to be incorrect and memory loss may be completely reversible.  For instance people suffering from normal pressure hydrocephalus have a condition that is completely amenable to surgical correction.

Another gratifying aspect of working with Alzheimer’s patients is being able to give their families and loved ones a clear indication of what the treatment options are and what the outcomes are likely to be.  In addition family members are often concerned about their own risk for developing the disease it now being common knowledge that the disease has a familial aspect.

All in all there is much to recommend a profession working and caring for Alzheimer’s patients. Our elderly are frequently amongst our most valued citizens who have contributed to the prosperity and safety of subsequent generations.  Continuing to work for their immediate care and finding new treatments to improve their long term prognosis are the premier interests of the Roskamp Institute’s researchers, physicians and clinicians.

Michael Mullan, M.D., Ph.D., Roskamp Institute director who, with associate director Fiona Crawford, Ph.D and lead scientist Daniel Paris, Ph.D., led the research team that developed the drug. Mullan said, “We need many more medicines to move forward into advanced clinical trials in the fight against Alzheimer’s Disease and we are pleased the Roskamp institute has played such a major role in the development of this drug.” Before a drug can move into clinical practice, Phase III is usually the last step in the regulatory process.

The clinical trials will take place in Europe, where Brian Lawlor, M.D., Connolly Norman Professor of Old Age Psychiatry at Trinity College Dublin, Ireland, will be principal investigator and coordinator. The study will be funded by the European Commission Seventh Framework Programme and more than 20 European clinical sites will participate. Nilvadipine is already approved for the use in mild cases of hypertension (high blood pressure) and Mullan says, “The process can move more quickly in Europe, and the study findings may help accelerate the process with the U.S food and Drug Administration (FDA).

Mullan and Crawford have been studying Alzheimer’s disease for more than 20 years, moving from the UK to Florida in 1991 and to Sarasota in 2003 to establish the Roskamp Institute. “Some of our recent studies have involved Sarasota area residents, who have contributed to our understanding of Alzheimer’s disease and helped move the development process forward,” said Crawford. Now, the Roskamp Institute will provide research support for the Phase III clinical trial, such as assessing genetic and other markers for Alzheimer’s disease in study participants.

For more information on Alzheimer’s Disease please visit www.mullanalzheimer.com

Or http://mullanalzheimer.info

Or www.rfdn.org

Fiona Crawford, Ph.D., associate director of the Institute, a leading research facility for Alzheimer’s disease and other neurological disorders says, “We have found that there are changes in blood proteins that occur after a head injury, and that these are dependent on the severity of the injury, the time since the injury and genetic factors influencing outcomes after head injury.” Crawford’s research indicates that TBI can affect cellular mechanisms in the brain long after the original trauma, and that blood biomarkers reflect these ongoing processes. She also stated, “Translating these finding from the laboratory to human patients may help clinicians determine the extent of the brain injury, how long ago the injury occurred and the patient’s prognosis for a favorable or a poor outcome.”

Traumatic brain injury has multiple consequences at the cellular level and so molecular changes can persist for weeks and months after the initial brain swelling and other immediate issues have resolved. Crawford says, “Identifying blood biomarkers of mild TBI would improve medical management by enabling us to identify patients who need treatment or intervention, even if they do not have obvious signs of a brain injury.” The U.S. Department of Defense, and the Veterans Administration supports all of Crawford’s work because it could lead to better diagnosis of military personnel with mild brain injuries and better long-term care of our veterans.

For more information on Alzheimer’s Disease please visit www.mullanalzheimer.com

Or http://mullanalzheimer.info

Or www.rfdn.org

The Roskamp Institute, under the leadership of Drs. Michael Mullan and Fiona Crawford, is dedicated to finding new treatments and cures for Alzheimer’s disease and related disorders.

Microcirculation. 2011 Jul;18(5):373-9. Epitope-dependent effects of Beta-amyloid antibodies on Beta-amyloid clearance in an in vitro model of the blood-brain barrier. Bachmeier CJ, Beaulieu-Abdelahad D, Mullan M, Paris D.

For more information Please visit:
<a href=’http://www.rfdn.org’>http://www.rfdn.org</a>
<a href=’http://www.mullanalzheimer.com’>http://www.mullanalzheimer.com</a>
<a href=’http://www.mullanalzheimer.info’>http://www.mullanalzheimer.info</a>

michael mullan, alzheimer, mullan alzheimer, mullan roskamp, roskamp institute, amyloid

Roskamp Institute aids high school students in genetic research

Roskamp aids high school students in genetic research

Read more: http://www.bradenton.com/2011/11/14/3649043/bridging-the-gap.html#ixzz1dgyk7Niz

The Roskamp Institute, headed by Drs. Michael Mullan and Fiona Crawford is dedicated to finding new treatments for Alzheimer’s disease. Drs. Mullan and Crawford were among those who first showed that certain early onset forms of Alzheimer’s are caused by accumulation of Alzheimers Abeta peptide. These findings contributed to the worldwide use of models of Alzheimer’s disease which contain human mutant amyloid precursor protein.

Eur J Pharmacol. 2011 Sep 19. [Epub ahead of print] Anatabine lowers Alzheimer’s Aβ production in vitro and in vivo.
Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.

For more information please visit:

<a href=’http://www.rfdn.org’>http://www.rfdn.org</a>
<a href=’http://www.mullanalzheimer.com’>http://www.mullanalzheimer.com</a>
<a href=’http://www.mullanalzheimer.org’>http://www.mullanalzheimer.org</a>

http://youtu.be/B3rfLOSqWls

Dr. Fiona Crawford — Discussion of research programs underway at
Roskamp Institute with Veterans and current combat military personnel
Dr. Michael Mullan – Research and treatment being done in
Alzheimer’s Disease, dementia, depression, and related disorders
Dr. Andrew Keegan – Associate Director, Roskamp Institute Clinic
Memory screens, clinical trials, neurological services
Tours available of Roskamp Institute Research Laboratory
Veteran’s Administration representatives will be on site
Information tables and Roskamp Institute personnel to discuss clinic services,
memory screens, clinical drug trials and volunteer opportunities.

Abeta Amyloid Mullan AlzheimerAlzheimer’s disease (AD) is the most common type of dementia in the elderly. AD is mainly characterized by the accumulation of a small molecule (known as amyloid beta (Ab)) in the brain. Many researchers have shown that the molecule CD40L is elevated in AD patients. Roskamp Institute Alzheimer’s research group headed by Dr. Michael Mullan also have recently shown that CD40L stimulation increases Ab levels in cellular models of the disease. Furthermore, Mullan’s Alzheimer group has shown that CD40L stimulation of cells that are important for the defense of the nervous system induces increases in pro-inflammatory molecules known as cytokines. The granulocyte macrophage colony stimulating factor (GM-CSF) is one of these cytokines involved in inflammation responses in the brain. Numerous studies have correlated AD with increases in pro-inflammatory cytokines. In the cytokine paper, we have shown that CD40L stimulation increases the levels of both GM-CSF and Ab in AD cell models. We have shown that treatment of these cells with GM-CSF causes a time dependent significant increase in Ab levels. We demonstrate that blocking GM-CSF reduces CD40L-induced Ab production in a dose dependent manner. In addition, we show that inhibiting GM-CSF signaling by silencing the GM-CSF receptor gene significantly reduces Ab levels to below basal levels in non-CD40L-stimulated by blocking the trafficking of Ab’s mother protein, the amyloid precursor protein. Our results that are now published in the Journal cytokine (Volmar et al., in press) suggest that GM-CSF operates downstream of CD40/CD40L interaction and that GM-CSF modulates Ab production.

Please visit Mullan Alzheimer website for new information: (http://www.mullanalzheimer.com)

For more details read the journal article at:

Patel NS, Quadros A, Brem S, Wotoczek-Obadia M, Mathura VS, Laporte V, Mullan M, Paris D. Amyloid. 2008 Mar;15(1):5-19.

Also please visit Mullan Alzheimer website for new information: (http://www.mullanalzheimer.org)

The Roskamp Institute is devoted to understanding causes of and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. Based in Sarasota, Florida, the Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease.

Headed by Dr. Michael Mullan, the institute employs experienced and interdisciplinary scientists and technicians and houses state-of-the-art research labs and equipment to conduct scientific research. The quality of research performed at the institute reflects its motto: “Better science. Real discovery.”

Michael Mullan is a biomedical researcher of the β-amyloid protein and its relation to Alzheimer’s disease. Mullan’s Alzheimer research is well known among Biomedical Community. Dr. Mullan Alzheimer research work resulted in identifying the most widely known Swiss Mutation that is present in familial form. Transgenic Animal for Alzheimer Disease uses Swiss Mutation.

Dr. Mullan is currently the director^[1] of the Roskamp Institute in Sarasota, Florida. Under Dr. Mullan’s guidelines the institute is carrying out cutting edge research in Alzheimer’s, Traumatic Brain Research, Gulf War Illness and other neuropsychiatric disorder.

Please visit websites to learn about Dr. Mullan Alzheimer’s Research Website:

• Roskamp Institute
• Mullan Alzheimer Research Notes
• Michael Mullan Wikipedia
• Roskamp Institute News
  

  Roskamp Institute Alzheimer Mullan Logo

Title:Disrupted-in-Schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1–neuregulin cascade

Journal: PNAS

5622–5627 | March 23, 2010 | vol. 107 | no. 12

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Title:The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer’s disease.

Journal : Biomaterials.

2010 Jul;31(21):5608-18. Epub 2010 Apr 28.

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The Roskamp Institute Memory Clinic and Clinical Trials Division provide a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

Title:NF-κB activity affects learning in aversive tasks: Possible actions via modulation of the stress axis

Journal: Brain, Behavior, and Immunity

doi:10.1016/j.bbi.2010.04.005

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

J. HUMPHREY, a B. O’STEEN, b R. HAYES, c A. ROSES, d M. MULLANa AND F. CRAWFORDa

aThe Roskamp Institute, 2040 Whitfield Avenue, 34243, Sarasota, FL,

USA

bCenter for Traumatic Brain Injury Studies, McKnight Brain Institute of

the University of Florida, 100 Newell Drive, Gainesville, FL, USA

cBanyan Biomarkers, 12085 Research Drive, 32615, Alachua, FL,

USA dR. David Thomas Executive Training Center, Duke University, One

Science Drive, Suite 342, Durham, NC, USA

Abstract—Traumatic Brain Injury (TBI) is known to result in oxidative stress, which is an increase or imbalance in the amount of cytotoxic oxidants and free radicals beyond what the cell can normally handle.  The Apolipoprotein E (APOE) gene has different variations called alleles, with two of the most common known as APOE3 and APOE4.  The different APOE alleles have been shown to influence outcome following TBI in different ways, with the APOE4 allele being associated with poor outcome, but through as yet unclear mechanisms, so we used transgenic APOE mouse models to examine the relationship between APOE genotype and oxidative stress following TBI.  Mice transgenic for either human APOE3 or APOE4 on a murine APOE-deficient background were examined in an approved model of TBI. RNA was prepared from the ipsilateral hippocampi and cortices retrieved at 24 h and 1 month post-TBI. Microarray (“gene chip”) analysis was performed on individual samples from three mice per group to determine the way different genes are turned on or off in response to TBI and to specifically investigate the response of genes involved in oxidative stress mechanisms. Our data demonstrated TBI-induced expression of many more anti-oxidant related genes in the APOE3 mice, suggesting a potential anti-oxidative role for the ApoE3 compared to ApoE4. However, in an additional cohort of mice we isolated the ipsilateral hippocampi, cortices, and cerebella at 1 month after TBI for immunohistochemical analysis of markers of oxidative stress: the formation and presence of carbonyls (indication of general oxidative modification), 3-nitrotyrosine (3NT; specific to protein modification), or 4-hydroxyl-2-nonenal (HNE; specific to lipid peroxidation). Although we observed significant increases in all three markers of oxidative stress in response to injury, and genotype was a significant factor for carbonyl and 3NT, we found no significant interaction between genotype and injury. This may be due to the overwhelming effect  injury has on the oxidative stress level compared to genotype in our ANOVA, but nonetheless suggests that an influence on oxidative stress response is not the primary mechanism behind the APOE-genotype specific differences of outcome following TBI.

To reach the article that was published in Neuroscience Volume 168, Issue 3, 14 July 2010, Pages 811-819, please follow the link.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Alex Bishop will be presenting the paper on Friday (6/11/2010) at Roskamp Institute.

Journal Club is held every Friday between 4 Pm-5pm. For change in schedule please check our twitter account or facebook page.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The journal club will start at 4:00pm on Friday (may 28th 2010) in the auditorium at Roskamp Institute.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

For more information visit S.T.E.M. website.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Published in J Neurochem. 2010 Jan;112(1):66-76. Roskamp Institute, Sarasota, Florida, USA. npatel@scripps.edu

Abstract

Beta-amyloid peptides (Abeta) are the major constituents of senile plaques and cerebrovascular deposits in the brains of Alzheimer’s disease patients. We have shown previously that soluble forms of Abeta are anti-angiogenic both in vitro and in vivo. However, the mechanism of the anti-angiogenic activity of Abeta peptides is unclear. In this study, we examined the effects of Abeta1-42 on vascular endothelial growth factor receptor 2 (VEGFR-2) signaling, which plays a key role in angiogenesis. Abeta inhibited VEGF-induced migration of endothelial cells, as well as VEGF-induced permeability of an in vitro model of the blood brain barrier. Consistently, exogenous VEGF dose-dependently antagonized the anti-angiogenic activity of Abeta in a capillary network assay. Abeta1-42 also blocked VEGF-induced tyrosine phosphorylation of VEGFR-2 in two types of primary endothelial cells, suggesting an antagonistic action of Abeta toward VEGFR-2 signaling in cells. Moreover, Abeta was able to directly interact with the extracellular domain of VEGFR-2 and to compete with the binding of VEGF to its receptor in a cell-free assay. Co-immunoprecipitation experiments confirmed that Abeta can bind VEGFR-2 both in vitro and in vivo. Altogether, our data suggest that Abeta acts as an antagonist of VEGFR-2 and provide a mechanism explaining the anti-angiogenic activity of Abeta peptides.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

A Thermo Engineer once told me that “Nano-LC is not for the faint-of-heart.” A 0.5µl bubble in a 10-port valve can make a mess of an experiment.  Incomplete proteolytic digestions can clog up your brand new $600 column and render it useless.  A few centimeters of post-column dead volume can cause significant peak broadening despite the fact that you have a $50,000 LC system.  The list of problems goes on and on.   This causes more than its share of heartache, which leads to this simple truth:

If the favorite pastime of proteomics researchers is bragging to one another about their latest and snazziest technological acquisitions, then the second favorite pastime is whining about how they don’t work.

Still, as time progresses, people chip away at old problems and find out how to do things better, faster, cheaper.  So this week, I’ll leave you with one less thing to cry about and describe HOW TO MAKE A BETTER HOMEMADE FRIT FOR FUSED SILICA COLUMNS.

I had originally learned to make frits by dipping a piece of fused silica into 75% KASIL and 25% DMF, however these frits were lengthy, un-reproducible, and lead to high back pressure and inconsistent chromatography.  That technique sucks.  Sorry, stinks.  No… wait… it sucks.

A new and improved protocol was first shared with me by Jennifer Busby and Valerie Cavett from Scripps.  They’re very smart, and you should read some of their papers. Go on… log on to Pubmed and get to reading.

It’s an adaption of earlier work by Maiolica et al (Proteomics 2005, 5, 3847–3850), and takes a whopping 2 minutes, and $0.25 of reagents from start to finish.  Well, that doesn’t include the ½ hour drying time, but if you’re saving that kind of time and money for a superior product, don’t complain!

OK, here goes…

1. Make a Kasil/formamide mix (75/25) and use approximately 2 µL to wet a glass microfiber filter (GC/F, Whatman).
2. Gently push and twist the end of a fused silica capillary onto the wetted filter.
3. Dry the frit for 5 minutes at approximately 37ºC or at room temperature for approximately 20 minutes before packing.  Note: times given for a 75 µm capillary; larger diameters may need longer to dry before packing.

Note: different column IDs may require a 2^nd glass fiber plug (do not wet this one) to ensure you don’t blow the frit loose.  To do this, first push the end of the fused silica tubing into a dry piece of filter and core out what you need, then repeat this on the wetted section of filter.  You may want to try this using 2 wetted cores, but that may lead to increased back pressure.  The only way to know is to try it out.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

A research study is being conducted in our area to evaluate an investigational medication for Alzheimer’s disease.

Qualified participants may receive:

- Study related medical care

- Study medication

- Compensation for time and travel

Please call now for more info:    Dr. Andrew Keegan

941-256-8018 ext. 353

The Roskamp Institute Memory Clinic and Clinical Trials Division provide a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

Abstract

Background: Ab deposits represent a neuropathological hallmark of Alzheimer’s disease (AD). Both soluble and insoluble Ab species are considered to be responsible for initiating the pathological cascade that eventually leads to AD. Therefore, the identification of therapeutic approaches that can lower Ab production or accumulation remains a priority. NFkB has been shown to regulate BACE-1 expression level, the rate limiting enzyme responsible for the production of Ab. We therefore explored whether the known NFkB inhibitor celastrol could represent a suitable compound for decreasing Ab production and accumulation in vivo.

Methods: The effect of celastrol on amyloid precursor protein (APP) processing, Ab production and NFkB

activation was investigated by western blotting and ELISAs using a cell line overexpressing APP. The impact of celastrol on brain Ab accumulation was tested in a transgenic mouse model of AD overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw) by immunostaining and ELISAs. An acute treatment with celastrol was investigated by administering celastrol intraperitoneally at a dosage of 1 mg/Kg in 35 week-old Tg PS1/APPsw for 4 consecutive days. In addition, a chronic treatment (32 days) with celastrol was tested using a matrix-driven delivery pellet system implanted subcutaneously in 5 month-old Tg PS1/APPsw to ensure a continuous daily release of 2.5 mg/Kg of celastrol.

Results: In vitro, celastrol dose dependently prevented NFkB activation and inhibited BACE-1 expression. Celastrol potently inhibited Ab1-40 and Ab1-42 production by reducing the b-cleavage of APP, leading to decreased levels of APP-CTFb and APPsb. In vivo, celastrol appeared to reduce the levels of both soluble and insoluble Ab1-38, Ab1-40 and Ab1-42. In addition, a reduction in Ab plaque burden and microglial activation was observed in the brains of Tg PS1/APPsw following a chronic administration of celastrol.

Conclusions: Overall our data suggest that celastrol is a potent Ab lowering compound that acts as an indirect BACE-1 inhibitor possibly by regulating BACE-1 expression level via an NFkB dependent mechanism. Additional work is required to determine whether chronic administration of celastrol can be safely achieved with cognitive benefits in a transgenic mouse model of AD.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Media Contact:

Cheryl Rindfleisch, Roskamp Institute

941-256-8018 x356

crindfleisch@rfdn.org or

Jeffree Itrich  858-622-5827

jitrich@ucsd.edu

May 10, 2010

Investigational Immune Intervention Slows Brain Atrophy in Alzheimer’s Patients

• 18-Month Phase 2 Study is First to Show Combined Benefits of IGIV on Clinical Outcomes and Brain-Imaging Measures

• Phase 3 Study Now Enrolling Participants at the Roskamp Institute in Sarasota

An investigational treatment, Immune Globulin Intravenous (IGIV), which utilizes naturally occurring antibodies in human blood has preserved the thinking abilities of a small group of mild-to-moderate Alzheimer’s patients over 18 months and significantly reduced the rate of brain atrophy. The study was conducted at the New York Presbyterian Hospital/Weill Cornell Medical Center and the results were presented at the American Academy of Neurology (AAN) annual meeting in Toronto in mid-April.

An important next step Phase 3 study of IGIV, called The Gammaglobulin Alzheimer’s Partnership (GAP) Study, is now underway throughout North America. Locally the study is being conducted at the Roskamp Institute in Sarasota, Florida. The Phase 3 study is a prospective, 18-month, randomized, double-blind, placebo-controlled, two dose arm of parallel groups in 360 subjects of both genders, aged 50-89 years old with mild-to-moderate Alzheimer’s disease (AD).

“The cognitive and functional outcomes and neuroimaging results from this 18-month Phase 2 study clearly support continued evaluation for Alzheimer’s disease in a larger number of patients,” says Dr. Paul Aisen, director of the Alzheimer’s’ Disease Cooperative Study at UCSD, one of the study’s sponsors. “The important next step is to fully enroll and complete the ongoing Phase 3 study in hope of confirming the Phase 2 findings and fully understand the potential benefit in AD.”

The Phase 2 study used Gammagard Liquid and Gammagard S/D for Alzheimer’s produced by Baxter Healthcare. The same products are being used in the Phase 3 Gap Study.

“IGIV is being evaluated as a possible treatment for AD because of its known antibodies to beta-amyloid, thought to be the major element of amyloid plaques in the brains of people with AD,” says Dr. Andrew Keegan, the study’s principal investigator at the Roskamp Institute.  “IGIV is not approved for treating AD but is approved in the U.S. and other countries for treating immune deficiency and autoimmune disorders,” he added. “It has been around for a long time and has an excellent safety record.”

Dr. Norman Relkin, director of the Memory Disorders Program at New York Presbyterian Hospital/Weill Cornell Medical Center and principal investigator of the Phase 2 study reported at the AAN that patients who received IGIV once or twice a month for 18 months had significantly lower rates of ventricular enlargement (6.7% vs 12.7% per year) and less whole brain atrophy (1.6% vs 2.2% per year) than control subjects who initially received the placebo. Relkin’s findings were based on two independent analyses of brain-imaging data from 20 patients who underwent serial MRI scans during the Phase 2 study of IGIV for Alzheimer’s disease (AD).

The brain of a typical AD patient shrinks three to four times faster than a healthy equivalent older adult due to the accelerated brain cell death. Shrinkage of brain tissue causes the fluid-filled ventricles at the brain’s center to enlarge at a faster rate than normal. Changes in the size of the brain and ventricles can be measured accurately by analyzing results from two or more MRI scans at intervals of several months apart. The unprecedented reductions in these measures after IGIV was administered in the Phase 2 study may indicate that IGIV exerts a disease-modifying effect that the current generation of AD treatments do not. Relkin found that rates of brain shrinkage were independent of the subject’s age, gender and brain volume at the beginning of the study but strongly correlated with IGIV dose and the clinical outcomes after 18 months of intervention. The research team also found that patients who responded best to IGIV did not measurably decline over 18 months, plus had an average rate of brain shrinkage and average rate of ventricular enlargement comparable to the rate of normal elderly adults.

“A dose related effect of an Alzheimer’s intervention on brain ventricular enlargement has never been seen before, and it suggests that IGIV may be sparing brain tissue,” says Dr. James Brewer, a neurologist and assistant professor in the neurosciences department at UCSD.

Dr. Diamanto Tsakanikas, a neuropsychologist at Presbyterian Hospital/Weill Cornell Medical Center conducted cognitive testing of the Phase 2 study participants while blinded to whether the patients received IGIV or placebo. Her testing revealed that AD patients who received uninterrupted IGIV for 18 months showed significantly less decline in their overall function and thinking abilities than AD patients who were initially given the placebo.

The pivotal Phase 3 study now underway at the Roskamp Institute is funded by Baxter and National Institutes of Health (NIH) through the Alzheimer’s Disease Cooperative Study (ADCS).

The Phase 2 study was supported by Baxter Healthcare, the Citigroup Foundation and The Clinical Translational Science Center of Weill Cornell Medical College.

For further information on the Phase 3 study go to www.GAPSTUDY.com or http://www.alzheimers.org/clinicaltrials/fullrec.asp?PrimaryKey=282 .

Local Site:

Roskamp Institute

(941) 256-8018

www.rfdn.org

Days-to-criterion as an indicator of toxicity associated with human Alzheimer amyloid-

Location: Roskamp Institute

Date: May 14th 2010

Time: 4:00PM

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Are you or someone you know suffering from memory loss or forgetfulness?

Roskamp Institute is offering FREE MEMORY SCREENING for adults age 60 or older.

For an appointment call:               Roskamp Institute

941-256-8018 ext. 349

The Roskamp Institute Memory Clinic and Clinical Trials Division provide a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

Int J Pept Res Ther (2010) 16:23–3.  DOI 10.1007/s10989-010-9198-8

Abstract: The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Ab peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts in nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell  proliferation as determined by Ki67 immunostaining were observed following treatment with the Ab fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Ab derivative peptide may constitute a new antitumoral agent.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Cytokine. 2008 Nov;44(2):283-7.

A continuous inflammatory state is associated with Alzheimer’s disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Abeta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Abeta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Abeta(1-40), levels of sCD40 and sCD40L are increased in AD and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with Abeta(1-42). We then combined sCD40, sCD40L, Abeta and APOE and found that this biomarker panel has high sensitivity and specificity (>90%) as a predictor of clinical AD diagnosis. Given the imminent availability of potentially disease modifying therapies for AD, a great need exists for peripheral diagnostic markers of AD. Thus, we present preliminary evidence for potential usefulness for combination of plasma sCD40, sCD40L along with Abeta(1-40) and APOE epsilon4 in improving the clinical diagnosis of AD.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

By Volmar CH, Ait-Ghezala G, Frieling J, Weeks OI, Mullan MJ.

Exp Cell Res. 2009 Aug 1;315(13):2265-74.

CD40, a member of tumor necrosis factor receptor superfamily, and its cognate ligand CD40L are both elevated in the brain of Alzheimer’s disease (AD) patients compared to controls. We have shown that pharmacological or genetic interruption of CD40/CD40L interaction results in mitigation of AD-like pathology in vivo in transgenic AD mouse models, and in vitro. Recently, we showed that CD40L stimulation could increase Abeta levels via NFkappaB signaling, presumably through TRAFs. In the present work, using CD40 mutants, we show that CD40L can increase levels of Abeta(1-40), Abeta(1-42), sAPPbeta, sAPPalpha and CTFbeta independently of TRAF signaling. We report an increase in mature/immature APP ratio after CD40L treatment of CD40wt and CD40-mutant cells, reflecting alterations in APP trafficking. In addition, results from CD40L treatment of a neuroblastoma cell line over-expressing the C-99 APP fragment suggest that CD40L has an effect on gamma-secretase. Furthermore, inhibition of gamma-secretase activity significantly reduces sAPPbeta levels in the CD40L treated HEK/APPsw CD40wt and the CD40-mutant cells. The latter suggests CD40/CD40L interaction primarily acts on gamma-secretase and affects beta-secretase via a positive feedback mechanism. Taken together, our data suggest that CD40/CD40L interaction modulates APP processing independently of TRAF signaling.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Development of the Barnes Maze as an Alternative to the Morris Water Maze Following TBI in Mice.

Scott Ferguson^1,2, Benoit Mouzon^1,2, John Phillips¹, Vani Ganapapthi¹, Alex Bishop¹, Gogce Kayihan^1,2, Venkatarajan Mathura^1,2, Michael Mullan^1,2 , Fiona Crawford^1,2

¹The Roskamp Institute, Sarasota, FL, USA; ² James A Haley Veterans Administration, Tampa, FL, USA

Traumatic brain injury (TBI) is suffered by approximately 1.4 million people in the United States each year. TBI is the leading cause of death and disability in the most active population (under 45 years of age) in industrialized countries. Within the military, TBI is associated with 59% of blast-associated injuries seen at Walter Reed Army Medical Center, and between January 2003 and May 2005, 31% of all admissions to WRAMC had a brain injury. Apolipoprotein E (APOE) polymorphisms are known to impact the outcome after TBI, with the APOE4 allele (and concomitant ApoE4 expressed protein) associated with worse outcome than ApoE3 following TBI.   As part of our TBI research program we are exploring the molecular, neurobehavioral and neuropathological outcome after TBI in mouse models of injury, including APOE transgenic mice.

In order to evaluate differential outcomes of injury and its effects on motor skills and memory, we have optimized a series of neurobehavioral tests in mice.  The Rotarod test measures motor skill and learning via a programmable rotating bar.  Rotarod has shown the ability to distinguish between injured and uninjured mice, and has shown appropriate trends between differing levels of injury.  Morris water maze is a test of spatial memory and learning originally designed for rats but later adapted for mice.  APOE3 mice performed better than APOE4 mice in our Rotarod results, demonstrating an APOE genotype-dependent effect on motor function following TBI.  However, in the cognitive paradigm not only did we fail to detect any APOE genotype-dependent effects, we observed no significant differences in performance between injured and uninjured mice.  We therefore explored other cognitive paradigms for their ability to discriminate between injured and uninjured mice.

The Barnes maze is analogous to the Morris water maze in that it is also a test of spatial memory and learning, but because swimming is not involved it is associated with less stress than MWM typically induces in mice.  Others have shown that there is a strain-dependent effect on the ability of mice to learn the water maze task as well as the Barnes maze task.  Given that C57BL/6J mice are reported to perform better on the Barnes maze task, and this is the background strain utilized in our research, we optimized a paradigm of the Barnes maze for use in our TBI studies.  Our results show a statistically significant effect of injury on the spatial memory and learning of C57BL/6J wild type mice.  Future studies will re-examine the effect of APOE genotype on spatial memory following TBI using this test.

This research was funded by a Department of Defense award (W81XWH-07-1-0700) to Dr. Fiona Crawford and by the Roskamp Foundation

APP is Internalized After CD40 Ligation Which Increases Aβ Production

Ghania Ait-Ghezala, Jeremy Frieling, Myles Mullan, Claude-Henry Volmar, and Michael J. Mullan.

CD40, a member of the tumor necrosis factor receptor superfamily, and its cognate ligand CD40L are both elevated in the brains of Alzheimer’s disease (AD) patients compared to controls. We have shown that pharmacological or genetic interruption of CD40/CD40L interaction results in mitigation of AD-like pathology in vivo in transgenic AD mouse models, and in vitro. Recently, we showed that CD40L stimulation could increase Aβ levels, but the mechanism causing this phenomenon is not known. Here we show that CD40 ligation triggers internalization of APP and that internalization by endocytosis is associated with increased Aβ production. Furthermore, anthocyanins, which are known to impact trafficking to and from lipid rafts, impair the production of Aβ by CD40L stimulated CD40. However, anthocyanins have no effect on CD40L treatment of a neuroblastoma cell line over-expressing the C-99 APP fragment suggesting that CD40L internalization has no effect on γ-secretase. This finding is consistent with previous data suggesting that endocytosis increases BACE activity. In summary, these data suggest that a general mechanism of increased Aβ generation may be lipid raft mediated internalization of APP allowing increased BACE activity on its substrate.

Neurobehavioral profiles of two mouse models of Gulf War Illness

Laila Abdullah¹, Alex Bishop¹, John Phillips¹, Benoit Mouzon^1,2, Scott Ferguson^1,2, Vani Ganapathi¹, Myles Mullan^1,2, Ghania Ait-Ghezala PhD^1,2, Michael Mullan MD, PhD^1,2 and Fiona Crawford PhD^1,2

Affiliations: ¹Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, ²James A. Haley VA Hospital, 13000 Bruce B. Downs Blvd, Tampa, FL, 33612.

Background: Gulf War Illness (GWI) is a multisymptom condition associated with service in the 1990-1991 Persian Gulf War conflict and affects around 250,000 US veterans. It is largely attributed to combined exposure to pyridostigmine bromide (PB) and overuse of pesticides and insect repellants.  After nearly two decades, there is still no treatment for GWI and the underlying pathologic factors associated with the observed central nervous system (CNS)-based symptoms in veterans remain unclear.  Current GWI animal models do not demonstrate the full spectrum of neurobehavioral features reported to be associated with GWI, which makes it particularly difficult to explore the efficacy of possible therapeutic options.  Therefore, we tested two different treatment paradigms in order to establish a mouse model of GWI, which exhibits motor, cognitive and anxiety-related symptoms that are observed in veterans with this illness.  Methods: For model A, a previously established treatment paradigm was used which showed pathological changes suggestive of neurodegeneration, however extensive neurobehavioral profiling was not performed. Treated C57BL6 mice received oral administration of 1.3mg/kg of PB in water, dermal application of 0.13mg/kg of permethrin (PER) and 40 mg/kg of N-N-diethyl m-toluamide 2 (DEET) in 70% ethanol and 5 minutes of restrained stress daily for 28 days, whereas control mice received vehicle for the same duration.  For model B, a new treatment paradigm was developed where CD1 mice in the treatment group were administered 2mg/kg of PB and 200 mg/kg of PER via i.p. in DMSO daily for 10 days and the control group received DMSO only.  Following treatment, neurobehavioral profiles were examined using the Rotarod test to assess motor deficits, the Open Field test for anxiety-related changes and the Morris Water Maze test to assess spatial memory.  Results: In model A, treatment was associated with significant impairment in sensorimotor function and presence of anxiety-related behavior, but there was no deficit in spatial memory.  In model B, a delayed adverse effect of treatment was observed on the outcome measures of anxiety and spatial memory, but there was no evidence of sensorimotor impairment.  Conclusion: These findings suggest that combined exposure to PB and pesticides/insect repellents may lead to CNS-based effects in mice that mimic some of the clinical symptoms observed in veterans with GWI.  Additional studies are required to determine whether all three neurobehavioral features can be produced in one mouse model and whether these changes correlate with pathological features associated with neurodegeneration.

Acknowledgment: Funding for this research is provided by a Congressionally Directed Medical Research award (GW080094) to Dr. Fiona Crawford.

Proteomic identification of plasma TBI biomarkers

Benoit Mouzon^1,2, Alex Bishop¹, Gogce Kayihan^1,2, Ben Katz¹, Scott Ferguson^1,2, Jon Reed¹, Venkatarajan Mathura¹, Michael Mullan^1,2 and Fiona Crawford^1,2

¹Roskamp Institute, Sarasota, Florida

²James A. Haley Veterans’ Hospital, Tampa, Florida

Traumatic Brain Injury (TBI) is a major cause of mortality and morbidity in both military and civilian populations. The current lack of prognostic biomarkers for TBI confounds treatment and management of patients and is of increasing concern as the TBI population grows.  As part of our TBI research program we are generating brain and plasma proteomic profiles from APOE3 and APOE4 transgenic mice which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI.  In this study we used proteomic approaches to identify the changes in plasma protein profiles in APOE3 and APOE4 mice following severe TBI, in order to determine peripheral biomarkers associated with a poor outcome after TBI.

Using a quantitative proteomics approach (isobaric tagging for relative and absolute quantitation – iTRAQ) we have identified proteins that are significantly modulated as a function of APOE genotype, injury and the interactive term of “genotype*injury”. Analysis of modulated plasma proteins revealed significant differences in proteomic response at 24 hours, 1 month and 3 months post injury across genotypes.  From these proteomic datasets we have identified 83 proteins at the 24 hour timepoint, 170 at 1 month and 129 at 3 months post TBI. For each timepoint, the identified proteins included those whose response was dependent on injury or the injury*genotype interaction, suggesting them as potential biomarkers of injury or outcome following injury.

In pilot validation studies, using antibody-based approaches in the original plasma from these mice, we have demonstrated the validity of our approach.  These preliminary data clearly demonstrate plasma protein changes that are not only injury-dependent but also interaction-dependent. The identified proteins include biomarkers that have been previously implicated in human TBI, and their time course and relationship to neurobehavior and pathology are now to be examined in these mouse models.  Importantly these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3 months time point, which is a considerable time post-injury in the mouse model and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury.  Furthermore, our identification of clusters of related proteins indicates disturbance of particular biological modules which increases their value beyond that of solitary biomarkers.  Clinical assays for many of these proteins are already established, which will facilitate translation of our findings from mouse to human.

The biomarker panels developed from this work will aid clinicians in the determination of diagnosis, prognosis, appropriate treatment and monitoring response to treatment, all of which are urgently needed in TBI management. The next step will be to investigate these potential biomarkers in human TBI patients and those studies will begin this year with the VA patient population and our clinical collaborators.

Acknowledgement:  This research was funded by a Department of Defense award (W81XWH-07-1-0700) to Dr. Fiona Crawford.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

Complex information that are available in a crude format make computational modeling and processing
a difficult objective in Biological and Health care research. Protocol revisions, process flexibility,
user adoptability should be considered in mind to develop an user friendly information management solution.
There is a great need to integrate data from several fields of research in a common platform to increase
process efficieny and reduce human errors. Realizing cost savings, application of knowledge mining tools on existing data and the need for data organization due to regulatory compliance, research groups and drug-discovery related industries are adopting electronic data capture and management solutions (EDC or EDM). Small scale setups still require an enterprise wide system that is both efficient, light weight, cost effective information management solutions that will be flexible to accomodate growth in the future. With the availability of field specific ontologies, controlled keywords/vocabularies, meta data management and language mapping tools, organization of unstructured data is becoming a feasible task. At the Roskamp Institute the Bioinformatics Group has developed several information management software to aid: Genomics, Proteomics, Animal Colony (Vivarium) and Clinical data management.

CliniProteus:
Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment.
Availability: http://www.rfdn.org/bioinfo/CTMS/ctms.html.

PWIMS 1.0: Proteomics Workflow and Information Management System

PWIMS is a software package that can systematically manage data in a proteomic laboratory setup. It is implemented in the LAMPP (Linux-Apache-MySQL-Perl/PHP) environment as a three-tier architecture. The client-tier is a web-browser that uses a thin-client HTTP to request resources and display responses to the user. The middle tier consists of an Apache web server, PHP scripting language, the Zend (PHP script) engine. The database tier uses MySQL RDBMS. Data Models and Entity-Relationships have been defined for handling data at various levels.

Some of the features of PWIMS are:

User Management: Multiple user settings, password authentication and access restriction depending on user role

Project Management: Project tracking, online availability of experiment status, experiment results, coordinators information, timeline and date records of the project.

Scheduling & Workflow Control: Tracks the workflow using unique codes for gels and target plates, controls workflow step-skipping and erroneous data entry, systematically schedules next step in the process, lists pending jobs

Data Capture: Form-based data entry, automatic mapping and transfer of large project files using FTP protocols, data can also be entered in a simple EXCEL sheet and uploaded

Data Integration & Analysis: Mass spec results are integrated to gels and projects. Protein hits can be filtered and exported for future reference or any other software, e.g., PDQuest. External links to UniProt, PUBMED, etc. are automatically provided

Data Mining & Presentation: Sequence motif search, functional keyword search and advanced queries can be specified. Results are made available for presentation and sharing.

GEMAT Genomics Experiment Management and Analysis Tool . GEMAT is an information management system designed as client-server tool for handling Affymetrix GeneChip information. It has builtin analytical tools for performing data mining and posting microarry data to endusers.

This will be the first in an ongoing series of technical tips for those interested in biochemistry and mass spectrometry.  Anyone involved with these fields knows there can be considerable headache and heartache that goes hand-in-hand with even the simplest of experiments.  Along the way, I’ve picked up quite a few tricks that I feel should be shared with others.  Most of these are pretty simple, and are intended to do one or more of the following: save time, save money, and improve your experiments.  I’d like to keep these segments informal.  After all, this is a blog and not a review article or method journal.

One recurring theme you will find will be (hopefully) the destruction of the “because we’ve always done it that way” mentality that pervades many laboratories.  This way of thinking runs counter-intuitive to everything the progressive nature of science strives to achieve, and stems from laziness and ego- neither of which have any place in a well-functioning lab.  Let’s face it though,  it’s going to be hard to get rid of lab egos.  We’re all nerds.  Some nerds think they’re not nerds.  Deal with it.

OK, now on to this week’s topic….

Western Blotting: Is methanol the be-all, end-all solvent for Western blotting buffers?

NO.  Not by a long shot.  It’s pricey and toxic.  You can find cheaper substitutes on the shelves of Walmart and Sam’s Club (if you live in the U.S., that is) that work just as well, if not better than MeOH – and you’re not paying the high prices charged by chemical companies.  It’s also ACS grade when sold in stores like that, so you don’t have to worry about it being junk.

So why is MeOH used almost exclusively for blots?

Oh wait…

“BECAUSE WE’VE ALWAYS DONE IT THAT WAY!”

I’m certainly not the first person to think of this, but I figure it warrants repeating.  Simply substitute isopropanol (IPA) for MeOH when preparing your Towbin’s buffer recipe.  Remember that most stores sell it at a 70% or 90% concentration, so be sure to adjust your volumes!   You can also use IPA to wet your PVDF membranes.

I’ll post some western blots run in IPA vs. MeOH, as well as images of the stained PVDF membranes so you can see the results for yourself.  What’s the point in changing things if they’re not as good or better than the original, right?

Other solvent sins: No matter what solvent you’re using for westerns, at no point should you use HPLC-grade solvents for blotting.  Good grief!  They certainly won’t ruin your experiments, but they will definitely ruin your budget, and I can’t tell you how many times I’ve seen labs doing this as a matter of routine.   Electrophoresis-grade buffers make perfect sense, but HPLC-grade solvents?  They make perfect nonsense.  Find a lesser-grade solvent in your catalog or simply head to the local megamart and compare prices (that’s right, you have to do some of the work here too).

So, if you’re running mass spectrometry experiments, now is not the time to be cheap with your solvents.  If you’re western blotting, that’s a different story.  Be bold, be cheap, be happy.

Next week: preparing frits for nano-LC columns.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

By Abdullah L, Luis C, Paris D, Ait-ghezala G, Mouzon B, Allen E, Parrish J, Mullan MA, Ferguson S, Wood M, Crawford F, Mullan M. These findings were published in Molecular Medicine 2009 Mar-Apr;15(3-4):95-100.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941)752-2949

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

Roskamp Laboratories, Department of Psychiatry, 3515 East Fletcher Avenue, University of South Florida, Tampa, Florida, 33613

Abstract

The β-amyloid (Aβ1–40) peptide has previously been shown to enhance phenylephrine contraction of aortic ringsin vitro.We have employed a novel observation, that Aβ peptides enhance endothelin-1 (ET-1) contraction, to examine the relationship between vasoactivity and potential amyloidogenicity of Aβ peptides, the role played by free radicals and calcium in the vasoactive mechanism, and the requirement of an intact endothelial layer for enhancement of vasoactivity. Rings of rat aortae were constricted with ET-1 before and after addition of amyloid peptide and/or other compounds, and a comparison was made between post- and pretreatment contractions. In this system, vessel constriction is consistently dramatically enhanced by Aβ1–40, is enhanced less so by Aβ1–42, and is not enhanced by Aβ25–35. The endothelium isnotrequired for Aβ vasoactivity, and calcium channel blockers have a greater effect than antioxidants in blocking enhancement of vasoconstriction by Aβ peptides. In contrast to Aβ-induced cytotoxicity, Aβ-induced vasoactivity is immediate, occurs in response to low doses of freshly solubilized peptide, and appears to be inversely related to the amyloidogenic potential of the Aβ peptides. We conclude that the mechanism of Aβ vasoactivity is distinct from that of Aβ cytotoxicity. Although free radicals appear to modulate the vasoactive effects, the lack of requirement for endothelium suggests that loss of the free radical balance (between NO and O−2) may be a secondary influence on Aβ enhancement of vasoconstriction. These effects of Aβ on isolated vessels, and reported effects of Aβ in cells of the vasculature, suggest that Aβ-induced disruption of vascular tone may be a factor in the pathogenesis of cerebral amyloid angiopathy and Alzheimer’s disease. Although the mechanism of enhanced vasoconstriction is unknown, it is reasonable to propose thatin vivocontact of Aβ peptides with small cerebral vessels may increase their tendency to constrict and oppose their tendency to relax. The subclinical ischemia resulting from this would be expected to up-regulate βAPP production in and around the vasculature with further increase in Aβ formation and deposition. The disruptive and degenerative effects of such a cycle would lead to the complete destruction of cerebral vessels and consequently neuronal degeneration in the affected areas.

Author Keywords: β-amyloid; vasoactivity; Alzheimer’s disease; cerebral amyloid angiopathy; endothelin-1.

The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA

author email corresponding author email

Journal of Neuroinflammation 2010, 7:17doi:10.1186/1742-2094-7-17
Published: 8 March 2010
Abstract
Background

Aβ deposits represent a neuropathological hallmark of Alzheimer’s disease (AD). Both soluble and insoluble Aβ species are considered to be responsible for initiating the pathological cascade that eventually leads to AD. Therefore, the identification of therapeutic approaches that can lower Aβ production or accumulation remains a priority. NFκB has been shown to regulate BACE-1 expression level, the rate limiting enzyme responsible for the production of Aβ. We therefore explored whether the known NFκB inhibitor celastrol could represent a suitable compound for decreasing Aβ production and accumulation in vivo.
Methods

The effect of celastrol on amyloid precursor protein (APP) processing, Aβ production and NFκB activation was investigated by western blotting and ELISAs using a cell line overexpressing APP. The impact of celastrol on brain Aβ accumulation was tested in a transgenic mouse model of AD overexpressing the human APP695sw mutation and the presenilin-1 mutation M146L (Tg PS1/APPsw) by immunostaining and ELISAs. An acute treatment with celastrol was investigated by administering celastrol intraperitoneally at a dosage of 1 mg/Kg in 35 week-old Tg PS1/APPsw for 4 consecutive days. In addition, a chronic treatment (32 days) with celastrol was tested using a matrix-driven delivery pellet system implanted subcutaneously in 5 month-old Tg PS1/APPsw to ensure a continuous daily release of 2.5 mg/Kg of celastrol.
Results

In vitro, celastrol dose dependently prevented NFκB activation and inhibited BACE-1 expression. Celastrol potently inhibited Aβ1-40 and Aβ1-42 production by reducing the β-cleavage of APP, leading to decreased levels of APP-CTFβ and APPsβ. In vivo, celastrol appeared to reduce the levels of both soluble and insoluble Aβ1-38, Aβ1-40 and Aβ1-42. In addition, a reduction in Aβ plaque burden and microglial activation was observed in the brains of Tg PS1/APPsw following a chronic administration of celastrol.
Conclusions

Overall our data suggest that celastrol is a potent Aβ lowering compound that acts as an indirect BACE-1 inhibitor possibly by regulating BACE-1 expression level via an NFκB dependent mechanism. Additional work is required to determine whether chronic administration of celastrol can be safely achieved with cognitive benefits in a transgenic mouse model of AD.

Int J Geriatr Psychiatry. 2009 Feb;24(2):197-201.

Suitable methods of earlier detection of memory changes, before the full onset of a dementia are needed.  Methods such as imaging for abnormal protein accumulation in the brain and lumbar puncture to measure abnormal proteins in cerebral spinal fluid are not likely to be useful for wide-scale use due to costs and the invasive nature of the procedure.  In this study, we examined the utility of a brief cognitive screen (the Montreal Cognitive Assessment; MoCA), compared to a widely used instrument (the Mini-Mental State Exam; MMSE) in detecting older adults living in the community experiencing significant memory decline and the early signs of dementia. One hundred and eighteen individuals, over the age of 70, participated in the project. The MoCA proved to be highly sensitive in identifying participants with memory problems.  The MMSE was ineffective in comparison. Brief screening instruments such as the MoCA provide an objective and cost-effective means of determining the need for further evaluation of memory changes in older adults at risk for dementia.

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

The Roskamp Institute provides a full range of services for individuals with Alzheimer’s disease including diagnostic work-up and follow-up treatment, neuropsychological examination, clinical trial opportunities, and memory screening.  For more information, please call (941) 256-8018.

After the town hall meeting, Dr. Carrillo toured the Institute’s laboratories and had lunch with the Institutes scientific and clinical staff where they discussed current scientific research and developments in the Alzheimer’s field.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.
For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

The brain of Alzheimer’s disease patients is characterized by the accumulation of a small protein called beta-amyloid or Abeta and by the presence of intraneuronal tangle of a protein called tau. Abeta appears to be a key player in the pathology of Alzheimer’s disease and has been shown to trigger memory impairment, neuronal loss, abnormal tau protein accumulation, as well as cerebrovascular damages in various animal models of the disease. Abeta is produced by the cleavage of a larger protein precursor by two different enzymes called beta and gamma-secretase. Beta-secretase is the rate limiting enzyme in the production of Abeta and is viewed as a golden target for the treatment of Alzheimer’s disease. However despite intensive work, direct inhibitors of beta-secretase or Gamma-secretase with good drug-like properties have been extremely difficult to make. Given the difficulties being encountered by pharmaceutical industries for developing direct secretase inhibitors, Dr. Paris hypothesized that drugs which indirectly target the beta-secretase by affecting the production of the enzyme rather than by inhibiting it would be beneficial. Following the development of a screening method for identifying such drugs, Dr. Paris’ research team identified that a small molecule called celastrol is an indirect beta-secretase inhibitor that can potently oppose the production of Abeta. Celastrol is a natural compound extracted from a perennial creeping plant indigenous to a large area in southern China and known as the “Thunder of god vine”. Extracts containing celastrol have been given to Chinese patients for many years and are known to be efficient against inflammatory conditions. In the present research, Dr. Paris will determine whether celastrol holds promise as a therapeutic agent for the treatment of Alzheimer’s disease. He will further investigate whether this compound can prevent or reverse cognitive deficits, Abeta accumulation and tau pathology that affect a transgenic mouse model of Alzheimer’s disease.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

It has long been known that Alzheimer’s disease is accompanied by inflammation, which both exacerbates and is caused by the underlying disease. In addition, it has long been suggested that abnormal deposits of a small protein, known as amyloid, which accumulate in the brain of those afflicted by Alzheimer’s disease, also trigger an inflammatory response. This inflammatory response is thought to be detrimental to nerve cells, eventually causing their destruction.

Recent research at the Roskamp Institute has revealed that inflammation can lead to the production of more amyloid, and researchers have found that a specific receptor on the nerve cell surface, known as CXCR2, is an interface between inflammation and new amyloid production. As specific inflammatory molecules contact CXCR2, a signal is generated which results in increased amyloid production. The presence of the abnormally occurring amyloid; therefore, contributes to its own reproduction through the inflammatory response it triggers.

“I found that by genetically knocking out CXCR2, we can reduce the amount of amyloid in various laboratory models and, by using drugs that specifically block the CXCR2 receptor, we are able to show that a decrease in production of amyloid can be achieved,” said Dr. Bakshi. “This study, which for the first time shows the early role of inflammation in AD, opens a new door for therapeutic intervention, potentially leading to the use of CXCR2 blocking agents as a way to treat both the inflammation and the amyloid production in Alzheimer’s disease.”

“Finding new classes of medications for Alzheimer’s disease is a world-wide priority,” said Michael Mullan, M.B.B.S., Ph.D., director of the Roskamp Institute. “Dr. Bakshi’s work highlights a new class of drugs that should have the benefit of both stopping inflammation and, importantly, stopping the accumulation of the pathologic amyloid. In addition to the drug Dr. Bakshi has already tested, she is making her own drugs to attack this potentially important target.”

Dr. Bakshi is currently a scientist II in the Roskamp Institute and leads the Laboratory of Chemical Biology and Drug Discovery in Neurology. Prior to the Roskamp Institute, Dr. Bakshi was a postdoctoral researcher with Dr. Michael Wolfe at Harvard Medical School, Center for Neurology from 2001-2004 and a sabbatical postdoctoral fellow at Harvard Medical School, Laboratory of Drug Discovery in Neurology with Dr. Michael Wolfe and Dr. Ross Stein from 2002-2003. Dr. Bakshi has a Ph.D. in Bioorganic Chemistry from the Center for Biochemical Technology, New Delhi, and a Master of Science in Organic Chemistry and Bachelor of Science in Chemistry from the University of Delhi, New Delhi.

The Roskamp Institute is a not-for-profit research Institute located in Manatee County and Hillsborough County, Florida, that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders and addictions with an emphasis on Alzheimer’s disease. The Roskamp Institute’s Memory Centers also offer comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

“Roskamp has always played a significant role in training and mentoring top quality students, and we are delighted to now have a formal degree-awarding program,” said Dr. Fiona Crawford, associate director of Roskamp. “With the enrollment of our first successful applicants, we look forward to further enhancing the Institute and its many partners and collaborators in Florida, as well as the local developing biotechnology community.”

“Our Ph.D. program brings the opportunity for postgraduate research students to participate in a one-of-a-kind program that will expose them to a world-class research facility,” said Dr. Michael Mullan, director of Roskamp. “They will work side-by-side with exceptional scientists, perform hands-on, laboratory-based research and gain the practical knowledge necessary to succeed in their area of research, and emerge as fully operational professionals.”

The Institute has enrolled three students in its Ph.D. program, which will expose them to Roskamp’s state-of-the-art technology and will allow them to gain knowledge of the Institute’s key divisions, including chemistry, proteomics and molecular biology. The first class of students in the program will pursue dissertation research on Gulf War Syndrome, Traumatic Brain Injury and Alzheimer’s disease.

Laila Abdullah, M.S., is a graduate of the University of South Florida with a Bachelor of Science in Biology and a master’s in Epidemiology. Abdullah is studying the biological cause of the chronic and complex health problems that Persian Gulf War veterans experience compared to other veterans, using both standard molecular biology and advanced proteomic technology.

Scott Ferguson is a graduate of the University of Central Florida with a Bachelor of Science in Micro/Molecular Biology. Ferguson is studying how brain proteins respond to traumatic injury in order to identify new ways to treat the long-term consequences of these injuries which are of such high prevalence in the military and civilian populations.

Nowell Ganey, who is a graduate of the University of Florida with a Bachelor of Science in Nutritional Science, is building on the seminal work of lead Institute scientists by exploring the mechanisms linking vascular factors to the development of Alzheimer’s disease.

OU has a 110 acre campus in Milton Keynes, England, and is also a distance learning university and the leading eLearning University in the U.K. for its quality of teaching. With the addition of Roskamp, there are 24 OU ARCs around the world. In addition to the research degree programs, OU is a very large teaching university. More than 2 million students have studied at OU since its inception in 1971. The OU is accredited by the U.S. Middle States Commission on Higher Education.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

The Team’s project highlighted some of the cutting edge research being carried out at the Roskamp Institute. The TSA team members from Southeast High are Maya Meredith, Andres Romero, Rachel Metras, Lor Gregor, Diego Corzo, John Nguyen, Marissa Bressi. As well, the team won first place in Florida for another Roskamp-assisted project in the Scientific Visualization category. Southeast High School is located in Bradenton, Florida and is an International Baccalaureate Diploma School.

Please click here to see video of this award wining work by the Team from Southeast High.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.
Videos

Initial research in experimental models and patients suggests that immunotherapy targeting beta amyloid (the protein that forms the core of plaques in the brain) may provide an effective way to treat AD. Antibodies that bind to beta amyloid are present in IGIV, which is made from the blood of several thousand healthy adults. This effort seeks the public’s participation in testing IGIV in a major clinical trial that is jointly funded by the National Institute on Aging and Baxter International Inc.

One of the hallmarks of AD pathology is an abundance of beta-amyloid deposits in the brain. While it is not yet known if beta amyloid plaques cause AD or are a byproduct of the disease, scientists are interested in finding ways to reduce the toxic effects of beta amyloid on the brain. Antibodies against beta amyloid may do so by binding to toxic forms of beta amyloid, thereby neutralizing them and/or promoting their elimination.

“We are investigating whether IGIV, which contains naturally occurring human anti-amyloid antibodies, will defend the brain of AD patients against the damaging effects of beta amyloid. If it does, giving IGIV to patients with mild to moderate Alzheimer’s may potentially slow the rate of progression of the disease,” says Dr. Andrew Keegan, the principal investigator for the study at Roskamp Institute.

“In our initial studies in AD patients, IGIV provided cognitive benefits, improved brain metabolism and reduced beta amyloid levels in the spinal fluid,” says Norman Relkin, M.D., Project Director and Director of the Weill Cornell Alzheimer’s Disease and Memory Disorders Program. In a Phase II trial at Weill Cornell, Dr. Relkin reported that participants undergoing several months of continuous IGIV therapy also demonstrated improvement in their activities of daily living. He added, “These findings, as well as IGIV’s established record of use for treating other diseases, provide a strong rationale for further study in AD patients on a larger scale.”

The GAP (Gammaglobulin Alzheimer’s Partnership) Study will examine the safety, effectiveness and tolerability of IGIV in patients with mild to moderate AD. GAP is recruiting 360 participants at 36 sites nationwide. This large Phase III clinical trial expands on earlier testing, is one of two Phase III trials, and is part of the final phase in studying IGIV as a potential treatment for AD before seeking regulatory approval.

The GAP trial is a double-blind, placebo-controlled study in which two-thirds of participants will receive IGIV and one-third will receive placebo. It will last up to 82 weeks. Sites are looking for study volunteers who fit the following criteria:

* Male or female, 50-89 years old
* Have been diagnosed with probable mild to moderate Alzheimer’s disease
* Have a study partner (spouse, child, sibling or friend) in contact with the participant 10 hours/week or more

The trial is being conducted by the Alzheimer’s Disease Cooperative Study (ADCS), a nationwide consortium of research centers and clinics coordinated by the University of California at San Diego and directed by Paul Aisen, M.D.

“As many as five million Americans may be afflicted now and with the numbers growing rapidly, ADCS clinical trials such as the GAP study are essential to finding new and more effective treatments for Alzheimer’s disease,” Aisen commented.

The ADCS is primarily supported by the National Institute on Aging (NIA), part of the National Institutes of Health. The GAP study is jointly funded by Baxter International Inc. and the NIA. For further information on the trial, please go to: http://www.adcs.org/Studies/IGIV.aspx

For more information on this study and Alzheimer’s disease, please visit the Alzheimer’s Disease Education and Referral Center website: http://www.alzheimers.org/clinicaltrials/fullrec.asp?PrimaryKey=282

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

Contact:
Dr. Andrew Keegan Jeffree Itrich
Roskamp Institute Alzheimer’s Disease Cooperative Study
email: rclinic @ rfdn.org email:jitrich @ ucsd.edu
Phone: (941)256-8018 Phone:(858)622-5827
www.mullanalzheimer.com www.adcs.org

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

More than 5.3 million Americans are living with Alzheimer’s, and every 72 seconds someone in America develops the disease. According to the Alzheimer’s Association, by mid-century someone will develop Alzheimer’s every 33 seconds, and there will be nearly a million new cases per year.

“With the country facing unprecedented economic challenges and a rapidly aging baby boomer population, now is the time to address the burgeoning Alzheimer’s crisis that triples healthcare costs for Americans aged 65 and over,” said Harry Johns, Alzheimer’s Association CEO.

Alzheimer’s disease is a neurodegenerative disorder characterized by progressive loss of memory and cognitive function. It destroys brain cells, causing problems with memory, thinking, and behavior that are severe enough to affect everyday life.

Experts believe that early detection of Alzheimer’s disease and early intervention with improved therapies provides the greatest opportunity to modify or halt disease progression. Most current therapies for Alzheimer’s treat the symptoms associated with it and not the disease itself.

“There is a rich, diverse variety of treatment possibilities for Alzheimer’s that scientists are exploring, offering great hope that drugs that may slow or even reverse disease progression could be on the horizon—saving millions of dollars in public health programs,” said Ronald Petersen, M.D., Ph.D, Alzheimer’s Association Medical Scientific Advisory Council Chair. On World Alzheimer’s Day, we renew our commitment to early diagnosis and aggressive Alzheimer’s research in order to improve the health outcomes for people living with this disease.

Dr. Andrew Keegan and other local physicians are currently researching potential new treatments for Alzheimer’s patients that target causes of the disease, such as amyloid plaques in the brain. The buildup of these plaques is thought to cause Alzheimer’s disease. Some of these investigational drugs use antibodies, or immune system proteins, to dissolve the plaques.

“There are too many lives, too little time, and too much at stake for anything less than an aggressive plan to address the threat of this disease,” Johns said.

Roskamp is a not-for-profit research Institute located in Sarasota, Fla., that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinic also offers comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

Contact:
Dr. Andrew Keegan
Roskamp Institute
email: rclinic @ rfdn.org
Phone: (941)256-8018
www.mullanalzheimer.com

For more information, please contact the Institute at (941) 752-2949, Roskamp’s Clinical Trials Division in Sarasota at (941) 256-8018 or visit www.mullanalzheimer.com.

In men, for instance, although there was an increase in the likelihood of having dementia over the age of ninety, it did not increase as much as it did in women. In women, the likelihood of having dementia doubled every five years after the age of ninety. Previous studies have suggested that the risk for dementia is higher in women than it is in men. But other studies have disputed this. This present study seems to confirm that the risk for women is greater than men, at least after the age of ninety years.

Therefore, if you divide dementia populations by sex over the age of ninety, about 45% of women will have dementia compared to 28% of men. Importantly the study also suggested that women who had used their brains (intellect) more throughout life and had achieved higher education, were much less likely to develop dementia than those who had not.

Understanding why women in this age group might be at higher risk will take additional studies. But it is known, for instance, that women are more likely than men to develop stroke and heart disease as they age. Both of these are independent risk factors for dementia and exacerbate Alzheimer’s symptoms.

Researchers at the Roskamp Institute are interested in finding new treatments for Alzheimer’s disease and clues from sex differences that confer different risks for Alzheimer’s are important because they may point to more treatment strategies.

Researchers have, for instance, speculated that estrogen is a protective factor for Alzheimer’s disease, but proactive treatment with estrogen has not been shown to be preventative in clinical trials. In the present study, the idea that vascular risk factors (which are more prevalent in women as they age) are contributory to Alzheimer’s is consistent with much of the work of Roskamp Institute scientists showing that in the presence of amyloid, damage to the vasculature is heightened and the consequences of vascular damage has greater impact on the brain in the presence of early Alzheimer’s disease than in normal individuals. These and other clues are leading Roskamp Institute scientists towards new treatments for the disease, some of which should be entering clinical trials in 2008.

It remains unclear to scientists why hypertension is a risk for Alzheimer’s disease, but we do know that in spontaneously hypertensive rats, there is a tendency to accumulate some of the pathology of Alzheimer’s disease.

In 1996, researchers at the Roskamp Institute discovered that the causative protein in Alzheimer’s (the amyloid protein) has a drastic effect on blood vessels. The effect is to increase the propensity of blood vessels to constrict. Subsequently, others show that after a small stroke (when blood vessels close down temporarily) the presence of amyloid tends to keep the blood vessels closed. It is assumed that the consequence of reduced blood flow to the brain, secondary to closed blood vessels, causes deprivation of oxygen and glucose to the neurons, thus causing more damage in a brain with high amyloid levels than one with not.

Translated into clinical terms, this means that the effect of a small stroke on somebody who is in the early stages of Alzheimer’s can be more devastating than somebody who is not. In fact, a study of nuns who were asked to complete mental state questionnaires in life and who subsequently died has revealed an important interaction between small strokes and the clinical signs of Alzheimer’s. Even though some nuns had amyloid deposits in their brain, they did not exhibit the symptoms of amyloid in life. Those nuns that had amyloid deposits but did exhibit the clinical symptoms of Alzheimer’s in life also had multiple small strokes.

Thus, damage to the blood vessels in the presence of amyloid is more devastating than if amyloid is absent. Hypertension tends to damage blood vessels throughout the body, but it is only in the brain that amyloid accumulates and can contribute to poor recovery after vascular injury.

What does this mean for patients treated at the Roskamp Institute? Patients are advised to take particular care to have their blood pressure and cardiovascular status monitored. High lipid or triglyceride levels can contribute to cerebrovascular (brain/blood vessel) damage and uncontrolled or poorly monitored high hypertension can also be highly detrimental. In addition, we know that other cardiac problems, such as arrhythmias can contribute to cerebrovascular damage, as mentioned, by throwing off small clots.

As we await effective treatments to combat Alzheimer’s directly, we need to ensure that we control other disorders which can contribute significantly to rapid declines in mental status. Interestingly, some antihypertensives seem to be able to control the risk for Alzheimer’s disease as well as controlling blood pressure.

Researchers at the Roskamp Institute have clearly shown that this does not apply to all antihypertensives and they are investigating why some are able to regulate both blood pressure and can reduce the incidence of Alzheimer’s disease while others cannot. This is an important area of research and clearly one that holds out hope for Alzheimer’s sufferers as the search for new treatments continues.

What does this mean practically? It means that someone in the early stages of Alzheimer’s will not remember information presented to them a short time ago. For instance, if somebody receives a phone call, a few minutes later they may not remember who it was who called. Similarly, if they set out for the grocery store, once they arrive there they may not remember what it is they set out for.

Today, we are so used to receiving news all the time from our computers, our televisions, radios, and mobile phones that we don’t realize that we are being presented with new information all the time. The Alzheimer’s sufferer is at a particularly grave disadvantage in this situation. Current events may escape their memory stores and a good test of whether someone may be suffering from the disorder or not is whether they can remember information that appears as news on television or other ways. So, for instance, knowing the big events in the campaign for the US presidential election will be registered by most of us and remembered. The Alzheimer’s sufferer may not know that Hillary Clinton has dropped out of the race nor that Barack Obama has been nominated. Knowledge of these events, which most of us take for granted are lost to the Alzheimer’s sufferer and thus monitoring our loved ones and friends for signs that they are not aware of current events may help us to detect early signs of the disease. Concern that somebody may not be acquiring new information should be a trigger to have them evaluated in a memory disorder clinic.

The Roskamp Institute has two such clinics – one in Tampa and one in Sarasota, Florida and they offer full evaluations for Alzheimer’s and other causes of memory loss.

Alzheimer, himself, saw the accumulation of amyloid protein in what are now know as plaques, but these accumulations of amyloid represent many, many single amyloid molecules aggregated together.

The researchers found that this highly aggregated form of amyloid was not injurious to memory. However, when the amyloid protein occurred in just a doublet, (i.e., two molecules of amyloid stuck together) then it was in its most toxic form. Single amyloid (which we all produce for much of the time) was harmless to memory. These findings are important because the doublet form of amyloid is soluble and therefore can travel freely throughout the brain. These findings also suggest that the aggregated form that is visible to the eye under the microscope is not the most important form for researchers to prevent.

These findings are of particular interest to researchers at the Roskamp Institute, who showed in 1996 that soluble forms of amyloid could be toxic to blood vessels, increasing the likelihood that they would constrict. This is a particularly bad thing, especially after stroke, and it raised the possibility at that time that the soluble forms of Aß of amyloid might be more important than the aggregated forms.

These new findings also suggest that treatments aimed at lowering the amount of the amyloid doublet, might be those that are most effective in the disease. The new vaccine treatment, for instance, aimed at lowering the amount of amyloid by soaking up the amyloid with an antibody, might be effective at lowering these amyloid doublets. Other drugs that are coming on-line for the treatment of Alzheimer’s also targeted at the amyloid protein will now, no doubt, be examined to see whether they can lower the amount of the amyloid doublet.

Researchers at the Roskamp Institute are dedicated to finding new treatments and cures for Alzheimer’s disease. They were among the first in the world to show that the amyloid protein was most likely central to the disease process. This theory is now being tested in clinical studies throughout the world with exciting recent results suggesting that, indeed, the removal of amyloid might be an effective treatment for the disease (see recent reports on Elan Pharmaceuticals).

The early findings by Roskamp researchers placed amyloid at center stage as the cause of the disease. Now Elan’s vaccine, which is targeted to soak up the amyloid protein, may be a verification that reducing amyloid accumulation is a way to tackle the disease. Although some researchers remain skeptical of the validity of this approach, the early results from Elan’s Phase II study, published this week (June 17) indicate that reducing amyloid levels with the anti-amyloid vaccine has slowed the rate of progression of the disease in some patients. Interestingly, the vaccine approach has been helpful in cases of the disease that do not have a high genetic risk loading. Although there was a hint that all cases of Alzheimer’s (even those with high genetic loading might benefit from the vaccine), there was not a statistically significant difference between placebo group and those individuals that carry an APOE4 gene. This gene is known to increase the likelihood of developing Alzheimer’s early in life and may represent a particularly aggressive form of the disorder. Nevertheless, the fact that there were trends in a treatment improvement in the high risk group and statistically significant improvement in income in the low genetic risk group, strongly suggest that targeting amyloid will be a therapeutically useful strategy.

For Roskamp Institute researchers the new data from Elan is very important as Roskamp Institute researchers have developed drugs that do the same thing as the vaccine, i.e., lower the accumulation of amyloid levels. One of those drugs is in clinical trials already in Europe and trials are set to begin in the US pending FDA approval.

For Alzheimer’s sufferers and Alzhiemer’s researchers alike, the news from Elan is very hopeful.

The study of the vaccine called bapineuzumab (AAB-001) in a Phase II clinical trial was conducted in mild to moderate Alzheimer’s disease. The clinical trial lasted eighteen months and overall the bapineuzumab appeared to have clinical activity in treating the disease.

The company found that although the study did not attain statistical significance on the primary efficacy endpoints in the total study population, it was shown that in Alzheimer’s patients who do not carry the APO lipo protein E4 (APOE4) version of the APOE gene there were statistically significant and clinically meaningful benefits associated with the vaccine. The endpoints used included the Alzheimer’s disease assessment scale (ADAScog), the neuropsychological test battery (NTB), the mini-mental state examination (MMSE) and the clinical dementia rating scale (CDR). Interestingly too, when the company looked at brain scans of Alzheimer’s patients in the trial, they found that the MRI indication of loss of brain substance was decreased in those patients that were treated versus the placebo group.

The Roskamp Institute (Institute) is engaged in a Phase III study of the vaccine for Elan Wyeth and these encouraging results suggest that the larger clinical trial may also be beneficial. The vaccine targets are a small protein called amyloid, which researchers at the Institute believe is associated and triggers the disease pathology.

In fact, researchers at the Institute were among the first in the world to show that an accumulation of amyloid could cause Alzheimer’s disease. This they did by working with early-onset families (where the disease occurs in the 40, 50, or 60 year age groups) and showing that genetic errors in the amyloid gene were all that was responsible for the early build-up of the amyloid protein in the brain.

The Elan Wyeth vaccine is engineered to identify amyloid and remove it from the body and as such, holds potential for halting the disease progression. It is expected that the vaccine would be given every few weeks throughout the life of the Alzheimer’s sufferer.

This and other innovative treatments are available to our clinic population at the Roskamp Institute.

The article importantly discusses the recent work of Elan and Wyeth and their vaccine approach to Alzheimer’s disease. The reason this is central to the work of the Institute is that the same target of the vaccine is the protein that was highlighted by Institute researchers in the early 1990s as being causal in the disease process. The protein called amyloid accumulates in the brains of those with Alzhiemer’s disease and early genetic studies by members of the Institute team showed that amyloid definitely could cause the disease in certain individuals. Articles published in Nature in the early 1990s verified the causal relationship between the buildup of amyloid and the development of Alzheimer’s disease.

Now, almost twenty years later, Elan and Wyeth have developed a vaccine called bapineuzumab, which targets amyloid and reduces its accumulation in the brain. Although the exact mechanism of the antibody vaccine is not known, it is believed to act as a sponge in the blood supply, sucking amyloid from the brain and disposing of it harmlessly around the body.

Interestingly, the Wall Street Journal article points out that although the vaccine Phase II study failed on some of its clinical endpoints, there was enough of a positive signal in the data to enthuse not only Wall Street but researchers world-wide that the lowering of amyloid may be an effective approach to stopping this devastating disease. Many drug companies world-wide are pursuing treatments for Alzheimer’s which lower amyloid. The Institute is one such not-for-profit group which has developed drugs which lower amyloid levels and which are now in clinical trials around the world.

It is estimated that the pharmaceutical industry and biotech companies will spend more than a billion dollars this year researching into new treatments for Alzheimer’s. A Phase III study for the vaccine is underway and is being conducted at clinical sites around the country, including the Roskamp Institute site in Sarasota, Florida. The Institute researchers and clinicians are gratified, not only that they contributed to the early understanding of the causes of Alzheimer’s disease, but that drugs now are coming into clinical trials that target amyloid and look as if they may well be effective in stopping this dreadful disorder.

Another very interesting aspect of the Phase II results from Elan and Wyeth, is that the vaccine seemed to have more benefit in some genetically non-predisposed individuals than others. A gene known as the APOE gene dictates our risk for Alzheimer’s disease, particularly regarding whether we are likely to get the disease when we are 65, 75, or 85. Two copies of the E4 version of APOE, for instance, increase the risk of getting the disease earlier in life. The Elan and Wyeth vaccine looks as if it wasn’t particularly effective in that group, although the numbers treated that were E4 carriers was quite small, as it is in the general population. However, for those not at high genetic risk, the results were significant in that, after eighteen months, there was statistically valuable reduction in the rate of decline of cognitive processes. Integrating genetic tests into clinical trials for Alzheimer’s disease has now become a standard and is one of the adjunct research tests conducted at the Institute.

The drug is designated ELND005 and the study is a phase two study in mild to moderate Alzheimer’s disease. ELND005 is an orally available drug that is designed to prevent the aggregation of the amyloid peptide. The amyloid peptide is thought to be central to the disease process in Alzheimer’s disease.

As the amyloid peptide accumulates in the brain in Alzheimer’s disease patients, it forms aggregates which are toxic to neurons. ELND005, which was formally known as AZD103, was developed in collaboration with transition therapeutics and has been shown to be able to reduce the amount of amyloid that accumulates in the brains of transgenic mouse models of the disease. This reduction in accumulation correlates with improved memory testing in such animals.

Phase I studies have already been completed in healthy volunteers with ELND005. The drug is shown to be well tolerated and crosses the blood/brain barrier. Importantly, ELND005 has been shown to reach CSF concentrations in humans that are equivalent to the effective mouse concentrations that can reduce the burden of amyloid in mice.

The Phase II study design includes three treatment arms and one placebo group. The treatment arms receive twice a day oral dosing of ELND005. The dose is either 250 mg, 1000 mg, or 2000 mg. The treatment phase will last for 78 weeks.

The endpoints of the study will include cognitive and functional testing of mild to moderate Alzheimer’s disease patients and MRI imaging of brain volumes. Quality of life measures will also be included. As in all Phase II studies, safety will be a primary measure throughout the clinical trial.

Clinical researchers at the Roskamp Institute are committed to bringing new drug treatments like ELND005 to our Alzheimer’s population. It is hoped that either this drug or others like it will play a significant role in the control of Alzheimer’s disease in the near future.

The Roskamp Institute is developing its own drug therapies for Alzheimer’s disease. One of which, nilvadipine, is currently under clinical trials in Ireland. This drug is shortly to be brought into clinical trials in the United States pending FDA approval.

The genomic analysis, which covers the examination of all the genes in the human genetic make-up allows research at the Institute to determine which genes respond in relation to exposure to certain drugs of addiction.

The proteomic analysis allows researchers at the Institute to determine which drugs of addiction trigger particular protein responses. The proteomic approach that the Institute adopts allows the researchers there to look at all the proteins in the human body in one go.

Changes in genomic and proteomic (gene and protein) profiles, enables the researchers to examine which particular profiles are associated with particular drugs. Moreover, by examining which genes and proteins are changed in response to drugs of addiction, it is expected that new methods to fight drug addiction will be developed. In particular, by knowing which proteins are switched on by particular drugs such as cocaine, heroin, or morphine, the researchers are able to determine whether there may be ways of blocking the addictive effects of these drugs.

Drug addiction impacts a very large part of American society and addiction to cocaine, heroin, morphine, and other drugs, including prescription drugs, is a persistent part of our culture. Developing new ways to combat addiction, both in the early stages and when it becomes chronic, is critical to help manage the devastating effect that addiction can have on the individuals concerned, their families, and their work colleagues.

The original funding to develop new insights into drug addiction and potentially new therapies came from the offices of National Drug Control Policy, which is in an executive branch of the federal government.

Currently, funding for drug addiction research at the Institute is provided by the Roskamp Foundation.

The officer reported remembering that the streets were unusually quiet, and he remembered making a radio call to others in the convoy warning them that something might happen. After the vehicle he was traveling in was struck by an improvised explosive device (IED), he remembers having thoughts of why he couldn’t see or hear and remembers wondering where he was. The blast had thrown him from his vehicle, causing a fractured skull and severe contusion of the left fronto-temporal area of his brain.

As one of the most damaging and dangerous consequences of Traumatic Brain Injury (TBI) is brain edema causing swelling of the brain, neurosurgeons performed a craniectomy removing a large piece of skull from the left temporal region, allowing the brain room to swell without being constrained. The compression of the brain in a confined space after a head injury can lead to severe complications, including death.

The next the officer remembers was waking up ten days later at the Walter Reed Hospital. Following treatment, including cognitive and speech therapy, this particular officer made a good recovery, but the article points out that others with similar head injuries do not do as well.

Researchers at the Roskamp Institute (Institute) have previously shown the recovery after TBI is partly controlled by a gene called the APOE gene. Variations in the APOE gene determine whether one will make a good or slow recovery after TBI. It is of interest to note that the same gene determines the risk of developing Alzheimer’s disease in older age groups. APOE may therefore be a general repair gene and current research at the Institute is examining the role of APOE and how it can influence recovery after head injury.

The Institute researchers hope to understand how APOE can, on the one hand increase rates of repair, or on the other hand, encourage degeneration after head injury. Such understanding may lead to the development of new treatments after TBI and may assist young officers, such as the one mentioned here, who suffer the effects of TBI while doing their duty.

This program is funded by the Department of Defense (DoD) as part of the DoD’s general strategy to find new treatments for soldiers who suffer from TBI. TBI is a common occurrence in the civilian population too and treatments developed for military personnel are likely to be extended very quickly for use in civilian population if shown to be successful.

The authors conclude that mild TBI, i.e. concussion, occurring among soldiers deployed in Iraq is strongly associated with PTSD and physical health problems three to four months after the soldiers return home. The authors point out that PTSD and depression are important mediators of the relationship between mild TBI and physical health problems.

Researchers at the Roskamp Institute (Institute) are seeking to find new treatments for TBI. In order to do this, they are examining the pathways which are disrupted after TBI to determine which genes and proteins are implicated in pathways of repair or of degeneration. Institute researchers are particularly interested in finding new medications that can intercept the degenerative pathways which occur after TBI. The Institute is devoted to finding new treatments and cures for Alzheimer’s disease (AD) and Institute researchers have a particular interest in the link between AD and TBI.

This report suggested that important contributors to Gulf War Syndrome included the nerve agent prophylaxis pill, pyridostigmine bromide, pesticide exposure and potentially anthrax vaccination. One of the recommendations that came out of this committee’s work was that new state-of-the-art technology should be applied to Gulf War Syndrome to try to understand the causes and potential cures of this disorder.

The Roskamp Institute, in collaboration with the Veteran’s Administration (VA), won a grant to pursue this end. The particular approach taken by the Roskamp Institute is to analyze Gulf War Syndrome at the cellular level. To do this, new technology known as proteomics is being used. Proteomic analysis basically allows researchers at the Roskamp Institute to visualize all the proteins which change in a cell after exposure to these potentially toxic agents. In partnership with the Tampa VA, the Roskamp Institute researchers and VA researchers are identifying which proteins characterize exposure to pyridostigmine bromide, organophosphate pesticides and anthrax vaccination.

It will of particular interest to understand which of the proteins that are observed to change after exposure to these agents are specific to the central nervous system. The long-term goal of this project is to understand why Gulf War veterans may be impacted by Gulf War Syndrome and what the underlying biochemical disturbance may be. This in turn, may allow avoidance of Gulf War-type syndromes in the future and may allow VA/Roskamp Institute researchers to consider protection against such syndromes in the event of exposure to nerve agent prophylaxis or pesticides or anthrax vaccination.

Original studies conducted by Elan focused on the former approach. Studies carried out in Europe, using an active approach, appeared encouraging in terms of the reduction of pathology of the disease and improved cognition. Unfortunately, however, several patients taking part in the clinical trials with the active vaccine died, most probably due to the vaccination.

At autopsy, it was clear that individuals had suffered a large inflammatory response in their brains. However, importantly, the amyloid deposits, which characterize Alzheimer’s disease, were diminished. This suggested that although the active vaccination was clearly dangerous, it was able to reduce the amyloid load in the brain, which is potentially a cure for Alzheimer’s disease.

A much more controllable way to deliver antibodies for amyloid is by passive vaccination. In this approach, antibodies are prepared outside of the human body and delivered intravenously every few weeks. This approach constitutes the new clinical trial being conducted by Elan Pharmaceuticals, including at the Roskamp Institute site. Although experimental, this approach is likely to be much safer than the active vaccine approach and offers real hope that this amyloid lowering therapy may be able to reduce the cognitive impairment (memory loss, disorientation, etc.) that invariably accompany the disease.

The Roskamp Institute is committed to delivering state-of-the-art therapies for Alzheimer’s disease as they appear on the market or in experimental clinical trials.

For more details read the journal article at:
Patel NS, Quadros A, Brem S, Wotoczek-Obadia M, Mathura VS, Laporte V, Mullan M, Paris D. Amyloid. 2008 Mar;15(1):5-19.

Keywords:

• alzheimers disease
• alzheimers disease assessment scale
• alzheimers disease end stage
• alzheimers disease symptoms
• symptoms of alzheimers disease
• alzheimers disease and
• alzheimers disease articles
• alzheimers disease care
• alzheimers disease diagnosis
• alzheimers disease fact
• alzheimers disease help
• alzheimers disease info
• alzheimers disease information
• alzheimers disease photos
• alzheimers disease picture
• alzheimers disease stage
• alzheimers disease statistics
• alzheimers disease support
• alzheimers disease test
• alzheimers disease type
• dementia alzheimers disease
• information on alzheimers disease
• prevent alzheimers disease
• symptom of alzheimers disease
• treatment for alzheimers disease
• alzheimer’s disease statistics
• alzheimer’s disease assessment
• alzheimer’s disease
• early onset alzheimer’s disease
• what is alzheimer’s disease
• alzheimer’s disease assessment scale
• alzheimer’s disease information
• information on alzheimer’s disease
• alzheimer’s disease articles
• alzheimer’s disease drug
• alzheimer’s disease and dementia
• alzheimer’s disease diagnosis
• alzheimer’s disease info
• alzheimer’s disease treatment
• alzheimer’s disease treatments
• causes of alzheimer’s disease
• stages of alzheimers
• signs of alzheimers
• stage of alzheimers
• early signs of alzheimers
• sign of alzheimers
• brain injury
• mild brain injury
• traumatic brain injury
• mild traumatic brain injury
• trumatic brain injury
• beta amyloid
• beta amyloid antibody
• anti beta amyloid antibodies
• anti beta amyloid antibody
• beta amyloid antibodies
• alzheimers
• alzheimers association
• what is alzheimers
• diagnosing alzheimers
• dementia vs alzheimers
• aluminum alzheimers
• information on alzheimers
• alzheimers donation
• alzheimers memory walk
• aids alzheimers
• alzheimers assoc
• alzheimers com
• alzheimers desease
• alzheimers picture
• alzheimers signs
• alzheimers test
• alzheimers testing
• alzheimers treatments
• alzheimers walk
• early alzheimers
• end stage alzheimers
• familial alzheimers
• alzheimers activity
• alzheimers and parkinsons disease
• alzheimers bracelet
• alzheimers brain disease
• alzheimers drug treatment
• alzheimers drugs
• alzheimers help
• alzheimers information
• alzheimers organization
• alzheimers patients
• alzheimers screening
• alzheimers store
• alzheimers symptom
• alzheimers symptoms
• book on alzheimers
• cure for alzheimers
• alzheimer s disease
• amyloid disease
• alzheimer disease
• cardiovascular disease
• disease
• vascular disease
• celiac disease
• coronary artery disease
• disease symptoms
• dementia disease
• parkinson disease
• parkinsons disease
• alzheimer disease history
• blood disease
• crohns disease
• stages alzheimer disease
• about alzheimer’s
• alzheimer’s association
• alzheimer’s info
• alzheimer’s information
• alzheimer’s statistics
• alzheimer’s treatments
• coping with alzheimer’s
• activities for alzheimer’s patients
• alzheimer’s activities
• alzheimer’s research
• alzheimer’s society
• alzheimer’s stages
• alzheimer’s symptoms
• early signs of alzheimer’s
• alzheimer’s treatment
• early onset alzheimer’s
• treatment for alzheimer’s
• treatments for alzheimer’s
• what is alzheimer’s
• alzheimer’s
• alzheimer’s stages of
• alzheimer’s diagnosis
• alzheimer’s diseases
• information on alzheimer’s
• alzheimer’s bracelet
• alzheimer’s care facilities
• alzheimer’s caregivers
• alzheimer’s cure
• alzheimer’s drugs
• alzheimer’s news
• alzheimer’s signs
• alzheimer’s support
• alzheimer’s support groups
• alzheimer’s test
• alzheimer’s therapy
• alzheimer treatment
• alzheimer treatments
• alzheimer society
• what is alzheimer
• alzheimer
• alzheimer s
• alzheimer association
• alzheimer symptoms
• alzheimer test
• activities for alzheimer
• activities for alzheimer patients
• alzheimer care
• alzheimer diagnosis
• alzheimer foundation
• alzheimer information
• alzheimer research
• alzheimer support groups
• early onset alzheimer
• dementia
• dementia activities
• dementia stages
• dementia care
• dementia symptoms
• symptoms of dementia
• what is dementia
• vascular dementia
• dementia support
• early dementia
• frontal lobe dementia
• lewy body dementia
• stages of dementia
• dementia research
• early onset dementia
• elderly dementia
• senile dementia
• amyloidosis
• head trauma
• roskamp institute
• brain injuries
• amyloid
• diseases
• head injuries
• brain stem injury
• cardiovascular diseases
• head injury
• closed head injury
• amyloid antibody
• roskamp
• amyloid antibodies
• amyloid diseases
• brain tumor
• brain trauma

Visit the Roskamp Institute site to learn more.

To learn more about this project please visit the Roskamp Institute’s news release.  You can also read more about this in the Tampa Bay Business Journal article titled “Roskamp Institute wins grant for lung cancer research.”

Visit the Roskamp Institute website to learn more about the research that it does.

Learn more at the Roskamp Institute website.

You can read more about the Biotechnology Legislative Caucus in the Tallahasee Democrat‘s article “Florida biotech industry leaders call for ‘next step’” and Bradenton Herald‘s “Biotech touted as key to future,” both of which were published today.

The Roskamp Insitute website also has more information.

For more information, see the press release “Roskamp Institute Opens its Doors to Neuroscience Doctorate Research Program” at mullanalzheimer.com.

For more information about this study and the Roskamp Institute, please contact Sarah Bascom or Kristen Bridges at (850) 222-2140 or www.mullanalzheimer.com.

The Roskamp Institute and EDC will work together in 2008 to foster a better environment for bio-tech companies in the county.

Visit Roskamp Institute’s press release about these developments for more information.

In the past, much work has linked hypertension to Alzheimer’s disease. For instance it is known that hypertension is a risk factor for Alzheimer’s disease. However, pure hypertension can cause a dementia distinct from Alzheimer’s by casing strokes. Stroke related dementia has a number of names (multi-infarct dementia, vascular dementia) but the basic idea is that hypertension results in bleeding into the brain. This bleeding due to hypertension and consequent rupture of blood vessels in the brain can be avoided if medications are taken to lower hypertension. Nilvadipine is one of the drugs that can do this and therefore is useful in preventing stroke related dementia.

Interestingly, aside from the risk for stroke related dementia, there is also an increased risk for Alzheimer’s disease in those people with hypertension. No one really knows why this link exists. Researchers at the Roskamp Institute previously showed that amyloid can increase the constriction of blood vessels in Alzheimer’s disease. This link may explain why there is a reduction in blood flow in Alzheimer brains – but there are likely to be other reasons as well. For instance, Roskamp Institute researchers have also shown that amyloid can also reduce the growth of new blood vessels in the brain – a process called angiogenesis.

The Roskamp Institute researchers have instigated this clinical trial using Nilvadipine as it shows beneficial effects in a number of pre-clinical and clinical studies. For instance, in addition to its anti-hypertensive effects, Nilvadipine has been shown to improve cognition (mental functioning) in patients in the early stages of the disease. In a clinical trial in Japan, Nilvadipine is compared with another common anti-hypertensive drug – Amlodipine – which is used in the US for hypertension. Both drugs lower blood pressure but compared to Amlodipine, Nilvadipine specifically improves blood flow in the brain and cognitive abilities in these patients.

The recent studies show that not all anti-hypertensives are going to be useful in Alzheimer’s disease. The work of the Roskamp Institute is very much in agreement with this as they have shown that many hypertension lowering drugs are unlikely to be helpful in Alzheimer’s disease. In fact, some are likely to be more harmful as they raise the amount of amyloid in the laboratory experiments. We will learn much more about the potential use of hypertension lowering drugs as the Roskamp Institute brings Nilvadipine into clinical trials in the United States for testing its use as a treatment for Alzheimer’s disease.

This panel is on Tuesday, October 9th at 4 PM, and a donation of $25 for the New College scholarship fund for women is charged for admission. Call 487-4800 for more information.

Among the soldiers who survive conflicts in Iraq and Afghanistan, the traumatic brain injuries account for a larger proportion of their casualties than in any other US war in recent history. According to the Joint Theater Trauma Registry, established by the U.S. Army Institute of Surgical Research, approximately 22 percent of the injured US soldiers received injuries to the head, face, or neck. A major reason for this high ratio of these injuries is Kevlar body armor and helmets. Although, it successfully protects these soldiers from bullets and shrapnel exposure, Kevlar helmets cannot fully protect the face, head, and neck areas. Additionally, it is also unsuccessful in preventing the closed brain injuries produced by blasts. Furthermore, among patients evaluated at Walter Reed hospital, closed head injuries outnumber other penetrating injuries (originally published in New England Journal of Medicine).

Most individuals with a mild traumatic brain injury improve entirely within a year, but moderate and severe brain injuries are more complex and have long-term consequences. The Center of disease Control and Prevention estimated that 5.3 million Americans are living with disabilities resulting from traumatic brain injury. Dr. Michael Mullan (Director of the Roskamp Institute) Dr. Fiona Crawford (Associate Director of the Roskamp Institute) and their team of scientists previously demonstrated that apolipoprotein E (APOE) influences traumatic brain injury outcomes. These Roskamp Institute scientists examined 110 participants from the Defense and Veterans’ Head Injury Program to determine a relationship between APOE genotype and memory performance on certain cognitive tests administered to these head injured soldiers. The memory performance was much worse in soldiers who had at least had one APOE epsilon 4 allele compared to those who did not. This Roskamp Institute team also determined that these findings were limited to memory and not other cognitive performances such as executive functioning. Therefore, these data support a specific role for the APOE protein in memory outcome following TBI, and suggest an APOE isoform-specific effect on neuronal repair processes (originally published in the journal Neurology).

Dr. Fiona Crawford received a Merit award from the Veteran’s Administration to further study, using genomics technology, the role of APOE in Traumatic Brain Injury. Dr. Fiona Crawford and her Roskamp Institute team have now completed the experiments showing differences in genomics response among the different mouse models after traumatic brain injury. Recently, Drs. Michael Mullan and Fiona Crawford received a prestigious award of $1.5 million from the Department of Defense which will allow the Roskamp Institute to investigate ApoE and other proteins to find potential peripheral biological markers and novel therapeutic treatments for traumatic brain injury. Florida Senator Bill Nelson recently toured the Roskamp Institute to observe its traumatic brain injury program in support of the soldiers affected by this devastating condition.

The Roskamp Institute is a world-renowned state-of-the-art research and clinical facility located in Sarasota Florida dedicating to finding novel therapeutics for treatment of neuropsychiatric disorder, especially Alzheimer’s disease, traumatic brain injury and substance abuse. The Roskamp Institute is supported by the funding from government agencies such the National Institutes of Health, the Veteran’s Administration and the Department of Defense as well as private donations from the Robert and Diane Roskamp Foundation.

read more | digg story

However, many people who care for loved ones with this condition have trouble finding time to obtain such training and pursue other support.   If you’re in this situation, this article may help.

roskamp roskamp institute alzheimers michael mullan

• The Roskamp Institute is Participating in a New Phase III MS Study to Evaluate the Efficacy and Safety of FTY720, a Novel, Investigational, Once-Daily Oral Medication (PR Newswire)
• The Roskamp Institute is Participating in a New Phase III MS Study to Evaluate the Efficacy and Safety of FTY720, a Novel, Investigational, Once-Daily Oral Medication (Red Orbit)
• The Roskamp Institute is Participating in a New Phase III MS Study to Evaluate the Efficacy and Safety of FTY720, a Novel, Investigational, Once-Daily Oral Medication (Forbes)

roskamp roskamp institute alzheimers michael mullan

SARASOTA, Fla., April 30 /PRNewswire/ — The Roskamp Institute announced today that it is now screening patients for enrollment in a new Phase III study to evaluate the efficacy and safety of FTY720 (fingolimod), a novel, investigational, once-daily, oral medication, in relapsing-remitting multiple sclerosis (RRMS). The 12-month, double-blind, randomized, active-comparator study, called “TRANSFORMS” (TRial Assessing injectable interferoN vS FTY720 Oral in RrMS) is sponsored by Novartis and will include approximately 1275 MS patients in more than 170 study centers worldwide.

“If the Phase III study program confirms the data demonstrated in the Phase II study program and leads to FDA approval, FTY720 may represent an improvement when compared to currently-available injectable medications,” said
Dr. Andrew Keegan, Principal Investigator.

Here are the full details.

roskamp roskamp institute alzheimers michael mullan

roskamp roskamp institute alzheimers michael mullan

Because people with Down’s syndrome have an extra copy of that chromosome, they produce more of the protein. A part of that protein, beta-amyloid, builds up as plaque on the brain.

“We may still get Alzheimer’s disease, but (the plaque) doesn’t start to accumulate until we’re 60, 70, 80,” said Dr. Mike Mullan, director of the Roskamp Institute Memory Center in Sarasota. “In Down’s syndrome, the plaque starts to accumulate when we’re 20, 30, 40, because there’s so much more of it being made.”

and

SF researchers are testing an Alzheimer’s skin patch that may have fewer side effects than a previously studied injectable medicine.

“We’re really now getting into a period where more and more drugs are going to come out on the market,” said Mullan. “I’ve counted at least 50 drugs in development that are about to be released into clinical trials. This is very good. This is very optimistic.”

Such drugs could also improve the overall brain functioning associated with Down’s syndrome – even for those who never develop Alzheimer’s. Stanford University research shows that the suspect gene may be generally destructive, not just in old age.

“That would make us think that perhaps in people with Down’s syndrome, we would want to try (Alzheimer’s) drugs very early in their lives,” Mullan said.

roskamp roskamp institute alzheimers michael mullan

Here’s a quote from Michael Mullan:

“We are looking for volunteers to participate in this pharmaceutical sponsored research study to assess the effectiveness and safety of the investigational drug fingolimod, used to treat patients with relapsing-remitting MS,” said Dr. Michael Mullan, director of the Roskamp Institute. “We hope by working with Novartis we may be able to provide our patients and their families with another treatment option.”

roskamp roskamp institute alzheimers michael mullan 

We are currently recruiting volunteers for our clinical trials, which are run by our Scientific Director, Michael Mullan, MBBS, Ph.D.  We are currently recruiting for clinical trials on the following diseases.

• Alzheimer’s Disease
• Dementia
• Mild Cognitive Impairment (MCI)
• Depression
• Epilepsy
• Head and Traumatic Brain Injury
• Migraine
• Multiple Sclerosis with or without Spasticity
• Neurodegenerative disease
• Neuromuscular disorders
• Parkinson’s Disease
• Tourette’s Syndrome
• Other psychiatric and central nervous system conditions
• Bipolar Disorder
• General Anxiety Disorder

If you are interested, please contact us here.

roskamp roskamp institute alzheimers

• Sarasota’s Roskamp Institute Discovers New Class Of Drugs That Can Impact Alzheimer’s Disease
  Medical News Today
• Roskamp Institute Discovers New Class of Drugs for Alzheimer’s Disease
  GEN News Highlights
• Sarasota’s Roskamp Institute Discovers New Class Of Drugs That Can Impact Alzheimer’s Disease
  Biocompare News
• Sarasota’s Roskamp Institute Discovers New Class of Drugs That Can Impact Alzheimer’s Disease
  FierceBiotech

roskamp roskamp institute alzheimers