A New Drug Reverses Lost Brain Connections in Alzheimer’s Disease

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Researchers at Sanford-Burnham Medical Research Institute have developed the first experimental drug named NitroMemantine that boosts brain synapses lost to Alzheimer’s disease. The medication combines two FDA-approved drugs to stop destructive cascades within the brain, which destroys the connections between neurons and ultimatly leads to memory loss and a decline in cognition.

Dr. Stuart A. Lipton, who lead the decade-long study, remarks that the research is focused on treating Alzheimer’s as a down-the-road target rather than on the amyloid beta plaques and neurofibrillary tangles, due to the latter’s few successes.  Operating under with this goal in mind, the study became based on findings that show NitroMemantine can restore synapses in the brain, which represent connections between neurons that have been lost throughout the progression of Alzheimer’s disease. Lipton also stated that these findings could mean a restorative synapse intervention not only during the onset, but also later during the disease’s cycle when a patient already has amylod beta plaques.  Conducted with animal models as well as in vitro with brain cells derived from human stem cells, Lipton’s team mapped pathways that lead to synapse damage in Alzheimer’s disease. These findings showed that amyloid beta peptides induce excessive amounts of glutamate, a neurotransmitter, resutling in the inhibition of memory and learning.  This excess glutamate activates extra-synaptic receptors, designated eNMDA receptors which then get hyperactive and can lead to loss of synapses. Previously, Lipton’s team had discovered a new drug known as Memantine which could be targeted to eNMDA receptors to slow down the hyperactivity caused by Alzheimer’s. However, Memantine’s chemical makeup leads to an overall positive charge, which often gets repelled from fellow postiveily charged diseased neurons.  A second drug, nitroglycerin, could bind successfully to another site on NMDA that Lipton’s team found. The new drug NitroMemantine represents the synthesis of these two drugs: Memantine selectively binds to NMDA receptors, leading nitroglycerin to target the receptor. Subsequent testing showed that while Memantine itself was flawed in restoring synapses, the combination of NitroMemantine was strong enough to revert numbers of damaged synapses back to normal within a matter of months in mice models, leading to a hopeful outcome of research regarding the disease.

Source:

  1. 1) Sanford-Burnham Medical Research Institute (2013, June 17). New drug reverses loss of brain connections in Alzheimer’s. ScienceDaily. Retrieved June 19, 2013, from http://www.sciencedaily.com /releases/2013/06/130617160849.ht

By Lauren Horne, Edited by Emma Henson

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