Bispecific nanobodies as a therapeutic for Alzheimers Disease

Michael Sierks (Inventor)

Research output: Patent


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
Original languageEnglish (US)
StatePublished - Sep 10 2009


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