New Class Of Alzheimer's Drug Identified
The Roskamp Institute today announced that its researchers have uncovered a new link between inflammation and Alzheimer's disease and have identified a potential target for developing novel therapeutics for intervention in this disease. The study, led by Roskamp Institute's Pancham Bakshi, Ph.D., is detailed in the American Chemical Society's Chemical Biology Journal, a leading online publisher of peer-reviewed research.
It has long been known that Alzheimer's disease is accompanied by inflammation, which both exacerbates and is caused by the underlying disease. In addition, it has long been suggested that abnormal deposits of a small protein, known as amyloid, which accumulate in the brain of those afflicted by Alzheimer's disease, also trigger an inflammatory response. This inflammatory response is thought to be detrimental to nerve cells, eventually causing their destruction.
Recent research at the Roskamp Institute has revealed that inflammation can lead to the production of more amyloid, and researchers have found that a specific receptor on the nerve cell surface, known as CXCR2, is an interface between inflammation and new amyloid production. As specific inflammatory molecules contact CXCR2, a signal is generated which results in increased amyloid production. The presence of the abnormally occurring amyloid; therefore, contributes to its own reproduction through the inflammatory response it triggers.
"I found that by genetically knocking out CXCR2, we can reduce the amount of amyloid in various laboratory models and, by using drugs that specifically block the CXCR2 receptor, we are able to show that a decrease in production of amyloid can be achieved," said Dr. Bakshi. "This study, which for the first time shows the early role of inflammation in AD, opens a new door for therapeutic intervention, potentially leading to the use of CXCR2 blocking agents as a way to treat both the inflammation and the amyloid production in Alzheimer's disease."
"Finding new classes of medications for Alzheimer's disease is a world-wide priority," said Michael Mullan, M.B.B.S., Ph.D., director of the Roskamp Institute. "Dr. Bakshi's work highlights a new class of drugs that should have the benefit of both stopping inflammation and, importantly, stopping the accumulation of the pathologic amyloid. In addition to the drug Dr. Bakshi has already tested, she is making her own drugs to attack this potentially important target."
Dr. Bakshi is currently a scientist II in the Roskamp Institute and leads the Laboratory of Chemical Biology and Drug Discovery in Neurology. Prior to the Roskamp Institute, Dr. Bakshi was a postdoctoral researcher with Dr. Michael Wolfe at Harvard Medical School, Center for Neurology from 2001-2004 and a sabbatical postdoctoral fellow at Harvard Medical School, Laboratory of Drug Discovery in Neurology with Dr. Michael Wolfe and Dr. Ross Stein from 2002-2003. Dr. Bakshi has a Ph.D. in Bioorganic Chemistry from the Center for Biochemical Technology, New Delhi, and a Master of Science in Organic Chemistry and Bachelor of Science in Chemistry from the University of Delhi, New Delhi.