Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases.

Abstract

A substantial and persuasive body of data now exists that supports the view that integrin alpha V beta 3 plays a critical part in activated macrophage dependent inflammation, osteoclast development, migration, and bone resorption, and inflammatory angiogenesis. All of these processes play an important part in the pathogenesis of rheumatoid arthritis (RA) and related arthropathies. Animal arthritis model data further support these concepts and also suggest that therapeutic antagonism of integrin alpha V beta 3 is worthy of further investigation in RA and related arthropathies. To this end, Vitaxin, also known as MEDI-522, has been developed. Vitaxin is a humanised monoclonal IgG1 antibody that specifically binds a conformational epitope formed by both the integrin alpha V and beta 3 subunits. It blocks the interaction of alpha V beta 3 with various ligands such as osteopontin and vitronectin. Clinical trials with Vitaxin in patients with RA are in progress.