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.
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Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.