Alzheimer’s Disease Drug development

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An article in the Wall Street Journal on the 18th of June 2008, encapsulates the current expectation, hope and knowledge in the field of Alzheimer’s disease research. Researchers at the Roskamp Institute (Institute) have been part of the history of the discovery of new possibilities for stopping this devastating disease.

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.