Bispecific Proteolytic Antibodies for Treating Alzheimer's

Project Summary

It is not yet certain that a vaccine to immunize patients with amyloid beta will be successful in fighting Alzheimer's disease. One reason is that not everyone who is immunized may produce an immune response. A potential new approach is called passive immunization. In this process, antibodies that bind to amyloid beta would be directly injected into AD patients. Dr. Sierks proposes the additional refinement of introducing an antibody that is genetically engineered to provide two different functions. The first function of the antibody is to bind to amyloid beta. The second function will be to break amyloid beta into two soluble fragments that can be cleared from the brain. Dr. Sierks' first step in producing such antibodies will be to identify cloned gene sequences of antibodies that will bind to certain regions of the amyloid beta protein. The next step will be to identify antibody sequences that break down the amyloid beta, and to introduce mutations that increase the activity and targeting of the antibody so that it breaks down amyloid beta but not other proteins. Finally, the antibody sequences will be combined into one molecule that can both target and cleave amyloid beta. If this project is successful, the new antibody can be further refined so it can cross the blood-brain barrier, setting the stage for preclinical testing.