"This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug," Samuel Gandy said. "We need more research to further clarify how dimebolin affects beta amyloid levels in the brain."
"A number of ideas need to be pursued. It may turn out that the drug works by getting toxic amyloid out of brain nerve cells. Or, the effects of dimebolin on other brain systems may override its effect on increasing beta amyloid. Finally, the drug's beneficial actions might have nothing to do with amyloid, which, if true, indicates the existence of important therapeutic targets independent of beta amyloid," Gandy added.
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Surprisingly, Dimebolin Increases Brain Beta Amyloid in Alzheimer's Mouse Models
Recent evidence suggests that dimebolin (Dimebon®, Medivation) may improve cognitive function in aged rodents and in people suffering from mild to moderate Alzheimer's, but how the drug produces these benefits remains unclear.
Samuel Gandy, MD, PhD, Mount Sinai Professor in Alzheimer's Disease Research; Professor of Neurology and Psychiatry; and Associate Director, Alzheimer's Disease Research Center at the Mount Sinai School of Medicine, New York, and colleagues John Cirrito PhD, and David M. Holtzman, MD, Professor and Chairman of the Department of Neurology at Washington University in St. Louis, MO, conducted a series of experiments in cells and in Alzheimer's mouse models to assess the effects of dimebolin on beta amyloid and other brain proteins known to be related to Alzheimer's disease.
Beta amyloid is a protein that is the main constituent of amyloid plaques found in the brains of people with Alzheimer's disease. It is widely considered a key player in the development and progression of Alzheimer's. The goal of anti-amyloid drugs that are currently in clinical trials is to reduce beta amyloid levels in the brain.
In a surprising result, the researchers at Washington University in St. Louis found that treatment with dimebolin caused an acute increase in brain beta amyloid levels in the animal models.
"This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug," Gandy said. "We need more research to further clarify how dimebolin affects beta amyloid levels in the brain."
"A number of ideas need to be pursued. It may turn out that the drug works by getting toxic amyloid out of brain nerve cells. Or, the effects of dimebolin on other brain systems may override its effect on increasing beta amyloid. Finally, the drug's beneficial actions might have nothing to do with amyloid, which, if true, indicates the existence of important therapeutic targets independent of beta amyloid," Gandy added.
The researchers note that so far they only studied acute systems, and it is conceivable that the chronic effect of dimebolin could be amyloid-lowering.
Sam Gandy, et al -- Dimebon®, A Clinically Promising Drug For Alzheimer Disease, Regulates Amyloid-Beta Metabolism In Cultured Cells, In Isolated Nerve Terminals, And In The Interstitial Fluid Of The Living Rodent Brain (Funders: Cure Alzheimer's Fund, National Institute on Aging)
About ICAD 2009
The 2009 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2009) brings together more than 5,000 researchers from 60 countries to share groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Association's research program, ICAD 2009 serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. ICAD 2009 will be held in Vienna, Austria at Messe Wien Exhibition and Congress Center from July 11–16.
Bob DeMarco is an Alzheimer's caregiver and editor of the Alzheimer's Reading Room. The Alzheimer's Reading Room is the number one website on the Internet for advice and insight into Alzheimer's disease. Bob taught at the University of Georgia, was an executive at Bear Stearns, the CEO of IP Group, and is a mentor. He has written more than 700 articles with more than 18,000 links on the Internet. Bob resides in Delray Beach, FL.
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