Special Report
Alternatives To Amyloid Plaque Theory Take Center Stage In 2008
"As a counterpoint to the continuing growth of the Alzheimer’s epidemic, currently estimated at 30 million worldwide and forecast to quadruple by the year 2050, in 2008 there was significant progress in the quest for more effective Alzheimer treatments."
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This AlzheimerVideoNews.com special report is presented in conjunction with the 2008 World Alzheimer’s Day, which occurs on September 21 of each year.
This special report by AlzheimerVideoNews.com is sponsored by the Institute for Neurological Research, a private medical group, inc., in Los Angeles, which has developed a new approach to Alzheimer’s disease using perispinal etanercept.
For More Information:
Institute for Neurological Research®, a private medical group, inc.
As a counterpoint to the continuing growth of the Alzheimer’s epidemic, currently estimated at 30 million worldwide and forecast to quadruple by the year 2050, in 2008 there was significant progress in the quest for more effective Alzheimer treatments.
First, the disappointing news. Two amyloid-based treatments for which there were high hopes, Alzhemed® and Flurizan®, failed in their phase 3 trials, casting a shadow on the current trials of another amyloid-targeted experimental treatment, bapenuzimab, whose development is being attempted by Elan Pharmaceuticals and Wyeth. The interim results for bapenuzimab were disappointing, resulting in a significant fall in the share prices of both Elan and Wyeth.
The latest experimental drug to disappoint was the drug being developed by AstraZeneca and Targacept, AZC3480, which failed to produce cognitive improvement in the key cognitive measure in the 12 week study, putting in doubt whether the companies will continue to pursue its development in Alzheimer’s disease. These results came on the heels of a widely reported study from England which some authorities said cast further doubt on whether removal of amyloid plaques from the brain should be the primary research focus of the Alzheimer community.
The disappointing news with Alzhemed®, Flurizan®, and from Elan, Wyeth, AstraZeneca, and Targacept was fortunately countered by the emergence of several innovative approaches to treatment of dementia that were reported at ICAD 2008, the world’s leading forum on dementia research, held in Chicago at the end of July.
At this meeting encouraging results for a drug originally used in Russia as an antihistamine, Dimebon®, were presented. The results were encouraging enough that on September 3, 2008 Pfizer acquired the rights to the oral drug from Medivation, a private company based in San Francisco. The most common side effects of Dimebon were dry mouth and depressed mood or depression. Depressed mood and depression are of particular concern as side effects, because these conditions often occur as part of Alzheimer’s disease and can severely compromise quality of life.
There was some concern that the lead author of the study, Dr. Rachelle Doody, disclosed that she had stock options in Medivation, the company that manufactured the drug; that the study was performed wholly in Russia; and that another of the authors of the study, Dr. Paul Aisen, also held stock options in Medivation. Fortunately, the conflicts of interest of Drs. Doody and Aisen were disclosed in the scientific article, published in Lancet, which reported the Dimebon results.
The issue of the propriety of academic researchers receiving financial consideration from pharmaceutical companies involved in developing experimental drugs is one which is of considerable concern. Senator Charles Grassley has been conducting an ongoing investigation into related issues involving academic researchers and the pharmaceutical companies.
In the case of Alzheimer’s disease, there may be some additional concern because Dr. Aisen is also the director of the national Alzheimer’s Disease Cooperative Study(ADCS). Dr. Aisen was appointed as director of the ADCS by the National Institute on Aging, which is part of the National Institutes of Health. Dr. Aisen, former Professor of Neurology and Medicine at Georgetown University, was originally trained as an internist and rheumatologist. While at Georgetown Dr. Aisen was the prinicipal investigator in the United States of Neurochem Inc.'s North American Phase 3 clinical trial for tramiprosate (ALZHEMED(TM)), which failed, resulting in Neurochem’s abandonment of any further efforts to clinically develop the drug.
All of these concerns aside, with Pfizer’s acquistion of the rights to Dimebon, further study in Alzheimer’s disease will be pursued. If U.S. studies confirm that Dimebon is of benefit, then Dimebon could become a much needed additional therapeutic agent.
Also at ICAD 2008, a new use for a reformulation of an older drug presented a tantalizing new possibility for Alzheimer’s disease. TauRX Therapeutics of Singapore, under the chairmanship of Claude Wischik, professor of psychiatric gerontology at the University of Aberdeen, Scotland, reported results of a phase 2 clinical trial conducted in the U.K. and Singapore utilizing Rember®. Rember® is a reformulation of methylene blue, an old drug never previously reported to be of benefit for Alzheimer’s disease.
The results reported at ICAD 2008 were quite encouraging, leading many to believe that it is possible that this approach, hypothesized to be due to effects on a new, non-amyloid target, the tau tangles in the Alzheimer’s brain, may eventually lead to a non-amyloid treatment approach to Alzheimer’s disease, if confirmed in Phase 3 studies.
Also at ICAD 2008, a new report of a positive clinical result using an innovative approach to dementia treatment was reported. Edward Tobinick MD from the Institute for Neurological Research, a private medical group, inc. in Los Angeles, presented the results of the use of perispinal etanercept in primary progressive aphasia, documenting rapid improvement in a patient with severe dementia. There is no FDA-approved treatment for this form of dementia.
Etanercept, a therapeutic approved for the treatment of rheumatoid arthritis and other immune-mediated disorders, was used off-label.
Etanercept is a member of a new class of therapeutic agents, the anti-TNF biologics, which target an excess of an immune molecule, TNF. In the brain Dr. Tobinick hypothesized that excess TNF interferes with communication between brain cells, and that this excess is centrally important to several forms of dementia, including Alzheimer’s disease. This new approach involves immune regulation of brain function, a tremendously exciting new area of brain research.
Despite the failures of several of the older anti-amyloid therapeutics, 2008 stands out because of the promise of these new therapeutics which address new targets in Alzheimer’s disease. Further study of these new therapeutic approaches is urgently needed, because none of the currently approved Alzheimer drugs has been shown to be capable of preventing long-term clinical deterioration.
Further information on the topics discussed today is available on the website of AlzheimerVideoNews.com. Visit AlzheimerVideoNews.com for the latest Alzheimer’s news, from around the world. Thank you for joining us.
For More Information:
Institute for Neurological Research®, a private medical group, inc.
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