Ken-Ichiro Fukuchi, M.D., Ph.D.
University of Alabama at Birmingham
Birmingham, Alabama

2003 Zenith Fellows Award

One potential approach to Alzheimer treatment focuses on generating an immune response to beta-amyloid. The first immunotherapy to reach clinical trials was a vaccine called AN-1792 that stimulated the recipient’s immune system to produce antibodies against beta-amyloid. Although AN-1792 showed promise in animal studies and early phases of human testing, Phase II trials were stopped after about six percent of participants developed inflammation of the brain and spinal cord. Preliminary data from one of 28 sites participating in this trial suggests that AN-1792 may have produced some cognitive benefit in individuals who developed anti-amyloid antibodies.

Finding other immunotherapeutic strategies that avoid AN-1792’s inflammatory side effects is an active area of research, and Ken-ichuro Fukuchi, MD, PhD, and his team are exploring one approach. The team has identified and isolated the genes for 10 human antibodies that react with beta-amyloid, then engineered variations of these genes that lack the portion of each antibody that induces inflammation.

Dr. Fukuchi and colleagues will inject the engineered genes into the muscle tissue of an animal model genetically engineered to produce human beta-amyloid. The animals’ muscle cells will incorporate the genes and begin producing the antibodies. After production, the antibodies will travel through the bloodstream to the brain, where the team will evaluate their impact on beta-amyloid levels and inflammation. Results may offer important clues about one approach to immunotherapy against beta-amyloid that avoids the serious side effects of previous strategies.