Study Reveals That Dimebolin Therapy May Contribute to Neuron Deterioration
A study led by Mount Sinai researchers suggests that dimebolin increases levels of beta amyloid, a protein related to the plaque buildup found in the brains of people with Alzheimer's.
Mount Sinai researchers have found that the antihistamine drug dimebolin (Dimebon), an experimental therapy that had been reported to improve cognitive function in patients with Alzheimer’s disease, may actually contribute to increased levels of beta amyloid in the brain, a protein that can contribute to neuron deterioration. These results are surprising given recent studies which had suggested that dimebolin could help enhance cognitive function. The study was presented at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna in July and has now been published in Molecular Neurodegeneration on December 17, 2009. The study was supported by the Cure Alzheimer’s Fund and the National Institute on Aging.
Sam Gandy, MD, PhD, the Mount Sinai Professor in Alzheimer’s Disease Research, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine, was the lead author of the study. Mary Sano, PhD, Professor of Psychiatry and the Director of the Alzheimer's Disease Research at Mount Sinai School of Medicine, served as a co-author, along with Michelle Ehrlich, MD Professor of Pediatrics, Neurology, and Genetics and Genomic Sciences, at Mount Sinai School of Medicine.
Using mouse models with Alzheimer’s disease, Dr. Gandy and his colleagues studied how dimebolin affects beta amyloid in cells, particularly in the synaptic contacts where nerve cells communicate. Beta amyloid accumulation leads to plaque buildup in the brain, or the formation of clumps called oligomers. These oligomers lead to impaired cognitive function. Dr. Gandy and his team found that the drug dimebolin increased beta amyloid in the spaces between nerve cells. John Steele, a graduate student at Mount Sinai School of Medicine - Graduate School of Biological Sciences, and Soong Ho Kim, PhD, a postdoctoral fellow in the Department of Neurology at Mount Sinai School of Medicine, were also members of the research team.
We must now conduct more mechanistic research to uncover why there are reported apparent benefits associated with dimebolin despite the fact that the drug acutely increases beta amyloid production, said Dr. Gandy. "Most beta amyloid researchers are seeking beta amyloid-lowering drugs. Yet, here is an agent that has appears to have a clinical benefit for up to 18 months in the face of acutely elevated beta amyloid production."
One possibility that researchers will investigate is whether the drug’s action on beta amyloid in the brain changes with extended drug use. The researchers note that only acute dimebolin use has been studied to date, and it is possible that further study could reveal a chronic effect that is beta amyloid-lowering.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses The Mount Sinai Hospital and Mount Sinai School of Medicine. The Mount Sinai Hospital is one of the nation’s oldest, largest and most-respected voluntary hospitals. Founded in 1852, Mount Sinai today is a 1,171-bed tertiary-care teaching facility that is internationally acclaimed for excellence in clinical care. Last year, nearly 50,000 people were treated at Mount Sinai as inpatients, and there were nearly 450,000 outpatient visits to the Medical Center.
Mount Sinai School of Medicine is internationally recognized as a leader in groundbreaking clinical and basic-science research, as well as having an innovative approach to medical education. With a faculty of more than 3,400 in 38 clinical and basic science departments and centers, Mount Sinai ranks among the top 20 medical schools in receipt of National Institute of Health (NIH) grants.