Translational Development of an ADAMTS-5 Antibody for Osteoarthritis Disease Modification

Larkin J, et al., 23(8):1254-66, Osteoarthritis Cartilage, 2015

This article describes generation of selective inhibitors that may help to understand the roles of aggrecanase (ADAMTS-4 and ADAMTS-5) in human osteoarthritis (OA). Accordingly, the inhibition of both recombinant and native aggrecanase activity by high affinity monoclonal antibodies (mAb) were determined. Additionally, features such as the target engagement and modulation of disease endpoints in human and other preclinical systems were also determined. Kinetic characterization of antibody-antigen interactions was achieved by an OctetQK system equipped with Streptavidin biosensors. The results suggest ADAMTS-5 as a protease involved in cartilage degradation. Also the mAb GSK2394002 selected against ADAMTS-5 shows the potential to be used as a disease modifying osteoarthritis drug.

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