Are we moving in the right direction with osteoarthritis drug discovery?

Abstract

Introduction: The success of targeted biologic therapy against rheumatoid arthritis has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis, in the hope of defining novel therapeutic targets. Osteoarthritis has long been thought of mainly as a degenerative disease of cartilage, with secondary bony damage and osteophytes. However, in recent years, the importance of the synovium, and in particular the synovial macrophages, has been highlighted in both in vitro and in vivo studies.

Areas covered: The recent progress in osteoarthritis drug discovery, particularly with regard to the search for therapeutic targets for this disease and the development of disease-modifying anti-osteoarthritic drugs is critically assessed. Some important recent research with regard to possible therapeutic targets in osteoarthritis drug discovery is highlighted.

Expert opinion: The concept that synovial macrophages and macrophage-produced cytokines, may play a role in driving inflammatory and destructive signalling pathways in osteoarthritis, is of importance for drug discovery in this disease, in spite of disappointing results from early studies of anti-cytokine strategies in osteoarthritis clinical trials. There is also an abundance of potential downstream therapeutic targets in osteoarthritis, including the matrix metalloproteinases, the aggrecanases, iNOS and elements of the Wnt pathway.

Keywords:

• disease-modifying drug
• interleukin-1
• macrophage
• osteoarthritis
• tumour necrosis factor alpha

Acknowledgements

This work has been supported by the Arthritis Research Campaign (UK), grants no. W0596, 13172, 14570 and 18893.

Notes

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