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2007 Grant - Fukuchi
Vectored Vaccines for Alzheimer's Disease
Ken-ichiro Fukuchi, M.D., Ph.D.
University of Illinois
2007 Investigator-initiated Research Grant
Amyloid plaques in the brain are a characteristic feature of Alzheimer pathology, and such plaques are partly composed of the protein fragment beta-amyloid. Because beta-amyloid itself is toxic to nerve cells, it was proposed that removal of beta-amyloid could slow or halt the progression of the disease. Clinical trials of this idea were performed using vaccines that caused a patient's own immune system to recognize and attempt to remove beta-amyloid from the brain. Preliminary results of these trials suggested that this concept worked, but the trials had to be halted because the vaccine caused inflammation in the brain, probably because of the immune response to beta-amyloid.
Dr. Ken-ichiro Fukuchi and colleagues have been working to refine the vaccine procedure against beta-amyloid so that it activates only a specific component of the immune system. By using this approach, they hope to develop a vaccine that will remove beta-amyloid from the brain without causing brain inflammation or other side effects. They have already developed a modified vaccine that appears to activate only a specific component of the immune system in mice. These mice are susceptible to developing Alzheimer-like symptoms, and initial evidence suggests that the vaccine improves the symptoms of disease in these animals. They have also found that treatment of the mice with a statin (cholesterol-lowering drug) reduces brain swelling and other side effects.
Neuropsychologists Dr. Fukuchi and Dr. Colyer plan to further test the safety and effectiveness of these strategies for vaccinating mice against beta-amyloid. These studies could lead to the development of a vaccine for treatment of humans who have early evidence of Alzheimer's disease.