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2008 - Levites
Single Chain Fragments as a Tool to Target Generic Amyloid
Yona Levites, Ph.D.
University of Florida
2008 New Investigator Research Grant
Beta-amyloid is a protein fragment that plays a central role in Alzheimer's disease. Small aggregates of beta-amyloid are suspected of being the prime culprits in Alzheimer pathology, and large aggregates form amyloid plaque, one of the characteristic features of Alzheimer's disease. Because various forms of beta-amyloid appear to be toxic to nerve cells, it has been proposed that removal of beta-amyloid from the brain may be an effective treatment for Alzheimer's disease.
Yona Levites, Ph.D., and colleagues are developing a molecular approach intended to remove beta-amyloid from the brain. Using mice as a model system, they have developed a technique for delivering molecules into the brain using a genetically modified virus. The researchers have used this system to deliver into the brain an antibody fragment that binds to beta-amyloid. Antibodies are large proteins that the immune system uses to recognize and remove foreign substances. When the researchers delivered their antibody fragment to mice that express beta-amyloid, it reduced the accumulation of amyloid plaque in the brain.
Dr. Levites and colleagues are now studying different antibody fragments to determine which is the most effective for reducing amyloid. They have designed antibody fragments that preferentially recognize beta-amyloid in plaque, in smaller aggregated forms or in both. They are planning studies to test which of these antibody fragments is most successful at reducing amyloid in the brains of Alzheimer-like mice. They will also test other aspects of their viral-delivery paradigm in an effort to optimize its effectiveness. These studies may yield a procedure for vaccinating mice against the development of Alzheimer-like pathology and determine whether such a procedure could be tested in clinical trials.