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2006 Grant - Rosenberg
Gene Vaccination for Therapy and Prevention of Alzheimer's Disease
Roger N. Rosenberg, M.D.
University of Texas Southwestern Medical Center
2006 Investigator-Initiated Research Grant
A tiny protein fragment called beta-amyloid is a key suspect in Alzheimer's disease processes that damage cell-to-cell communication and destroy cells in the brain. One experimental therapeutic strategy targeting beta-amyloid involved creating a "vaccine" based on a synthetic version of the fragment, which "trained" the immune system to recognize and attack beta-amyloid produced by the body. Early-stage human trials of this vaccine were stopped when some participants developed severe brain inflammation. In these participants, the vaccine excessively activated certain immune system cells involved in the inflammatory response.
Roger N. Rosenberg, M.D., and colleagues are working to develop a more effective Alzheimer immunization strategy with fewer side effects. They have produced a vaccine based not on a form of beta-amyloid, but on the gene that provides the blueprint for this protein fragment. In preliminary studies, Dr. Rosenberg's team injected their vaccine into mice genetically altered to develop Alzheimer-like symptoms. Results indicated that the vaccine (1) produced high levels of anti-amyloid antibodies, (2) did not excessively activate the immune system to cause inflammation, and (3) significantly decreased levels of beta-amyloid in the animals' brains.
For this grant, Dr. Rosenberg's team proposes to confirm the above findings by conducting a much more extensive vaccine study with genetically altered mice. If this study proves successful, the team then hopes to advance their experimental vaccine into a clinical trial enrolling people with Alzheimer's disease.