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2006 Grant - Wisniewski
Mucosal Immunization Therapy in Alzheimer's Disease in Mice
Thomas Wisniewski, M.D.
New York University
New York, New York
2006 Investigator-Initiated Research Grant
Beta-amyloid, a key suspect in Alzheimer pathology, is a primary target in drug development projects. Many efforts are under way to block its production, inhibit its toxic effect or clear it from the brain. One strategy is to develop a beta-amyloid-derived immunotherapy, or "vaccine," that trains the immune system to recognize and attack beta-amyloid in the brain.
While initial trials of this strategy seemed promising, the effort was halted because of severe side effects, particularly inflammation of the brain. Now researchers are investigating new strategies that may not result in dangerous side effects.
Thomas Wisniewski, M.D., and colleagues observed that the first vaccine worked primarily through immune responses mediated by cells in the brain that send out all-purpose clean-up crews, which are more likely to contribute to inflammatory side effects.
The researchers have developed a new immunotherapy that depends primarily on the body's specialized, "roaming" immune-system cells that have a more customized approach to ridding the body of disease agents. By activating this part of the immune system, there is less chance for inflammation. The investigators will test the new therapy in genetically altered mice that develop an Alzheimer-like disorder. The outcome of this work may provide evidence for developing future clinical trials.