Abstract

Antibodies to GPCRs A New Therapeutic Approach

Paul Insel, Vice-Chair and Distinguished Professor, Pharmacology, University of California San Diego

Antibodies to cell surface (plasma membrane) proteins have been developed and have proved to be highly useful as therapeutic agents in many clinical settings. Even so, G-protein-coupled receptor (GPCRs), the largest class of membrane signalling receptors and the largest class of targets for approved drugs, have not generally been targeted with such antibodies. Numerous efforts underway by academic groups and commercial enterprises seek to generate and validate GPCR-targeted antibodies as novel therapeutic approaches. These types of antibodies may be of particular utility in developing treatments directed at the large number (~120) orphan GPCRs, i.e., ones without known physiologic agonists, and for which it may be difficult to identify suitable small molecule drugs. This lecture will present initial results regarding one such orphan GPCR as a potential target in the treatment of pulmonary arterial hypertension, a disease setting in need of new therapeutic approaches.