Friday, December 3, 2021

Neurology/Neuroscience Research Seminar

12:00 PM to 1:00 PM

CME credit available, click here

Virtual event
Zoom ID: 910 4550 7427 Passcode: 829259

“Engineered Antibodies with Enhanced Brain Delivery and Targeting for Neurodegenerative Disease Applications”

Peter M. Tessier, PhD

Professor

There are now >100 approved antibody drugs and related products for treating a wide range of diseases, including the controversial antibody (aducanumab) for treating Alzheimer’s disease. A key reason for the success of antibody therapeutics is due to their attractive combinations of molecular properties, including their high affinity and specificity, low off-target binding and toxicity, and long half-life. Nevertheless, there are several challenges that continue to limit their development and use in therapeutic and diagnostic applications, especially those related to neurodegenerative diseases, that will be addressed in this presentation. First, the development of antibodies with extremely high specificity for misfolded proteins, such as aggregates of Abeta and tau linked to Alzheimer’s disease and alpha-synuclein linked to Parkinson’s disease, remains challenging and typically results in antibodies with sub-optimal combinations of molecular properties. We have developed a directed evolution approach that enables selection of antibodies with combinations of affinities and conformational specificities for protein aggregates that are superior to those of clinical-stage antibodies, including aducanumab (Abeta) and cinpanemab (alpha-synuclein). Second, the delivery of antibodies to the brain is strongly limited by the blood-brain barrier. We have developed a bispecific antibody shuttle approach that enables the delivery of off-the-shelf IgGs to the brain parenchyma at concentrations (0.1-1 nM) and timeframes (up to at least 7 days) that are useful for diverse therapeutic and imaging applications.