Bispecific nanobodies as a therapeutic for Alzheimers Disease

Alzheimers disease (AD) is one of the most prominent and feared neurodegenerative diseases associated with aging. A hallmark of this disease is the formation of extra-cellular amyloid plaques in the brain. The principle component of these extracellular plaques is amyloid- protein (A). Though the mechanisms underlying Alzheimers disease pathology remain controversial, accumulation and deposition of A appears to play a critical role in the pathogenesis of AD. Amyloid- protein is formed through cleavage of amyloid precursor protein (APP) by beta-secretase. Alternatively, cleavage of APP by alpha-secretase, results in a non-pathogenic outcome and no accumulation of A. A viable therapeutic approach therefore might be to facilitate the clearance and reduction of A by targeting these pathways. Researchers at Arizona State University have successfully synthesized a bi-functional recombinant antibody as a treatment for AD. The bi-specific construct is composed of two single chain antibody fragments (scFV): one that blocks beta-secretase activity by binding to the substrate APP (but not A), and a second that promotes alpha-secretase activity by specifically cleaving at the alpha-secretase site of A or APP. This invention may have significant potential as an effective therapeutic for AD. Potential Applications Antibody to treat Alzheimers Disease Benefits and Advantages Non-inflammatory: Antibody fragment is derived from a humanized library Specific: The antibody fragment binds to amyloid precursor protein without cross-reacting with amyloid- protein Bifunctional: The antibody fragment blocks formation of A and promotes non-pathogenic (alpha-secretase mediated) cleavage of amyloid precursor protein Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Sierks' directory webpage Dr. Sierks' laboratory webpage