The future of osteoarthritis therapeutics: emerging biological therapy

Abstract

Biological therapy is a thriving area of research and development, and is well established for chronic forms of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, there is no clinically validated biological therapy for osteoarthritis (OA). Chronic forms of OA are increasingly viewed as an inflammatory disease. OA was largely regarded as a "wear and tear disease". However, the disease is now believed to involve "low grade" inflammation and the growth of blood vessels and nerves from the subchondral bone into articular cartilage. This realization has focused research effort on the development and evaluation of biological therapy that targets proinflammatory mediators, angiogenic factors and cytokines in articular cartilage, subchondral bone and synovium in chronic forms of OA. This review article provides an overview of emerging biological therapy for OA, and discusses recent molecular targets implicated in angiogenesis and neurogenesis and progress with antibody-based therapy, calcitonin, and kartogenin, the small molecule stimulator of chondrogenesis.

Fig. 1

Schematic diagram summarizing current concepts in the biological treatment of OA

Fig. 2

Molecular structure of kartogenin ((2-[(biphenyl-4-yl)carbamoyl]benzoic acid; 4′-phenylphthalanilic acid (8CI); also known as KGN). Kartogenin is a cell-permeable biphenylcarbamoylbenzoate compound that potently induces the differentiation of mesenchymal stem cells (MSCs) into chondrocytes (EC50 = 100 nmol L⁻¹). It binds reversibly to the FC-1 fragment of filamin A and disrupts its association with core-binding factor β subunit (CBFβ) leading to the nuclear localization of CBFβ and binding to runt-related transcription factor (RUNX) to regulate chondrogenesis. PubChem CID: 2826191