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Rheumatoid arthritis affects about 1% of all populations, women two to three times more often than men. This translates to a total of 5 million rheumatoid arthritis sufferers in the major pharmaceutical markets. The market for agents used to treat rheumatoid arthritis totaled $1.6 billion in 2000. At present, treatments of this disease are based on symptomatic therapies such as NSAIDs (including the new COX-2 inhibitors), gold-containing compounds and corticosteroids. The current trend however is to move towards disease-modifying anti-rheumatic drugs (DMARDs). The matrix metalloproteinases (MMPs) are implicated in joint destruction and inhibitors of for example MMP-1 may provide therapeutic benefit. As an alternative to the use of inhibitors, blocking MMP-1 expression may also be of use. In a recent dossier we fully overview the ability of the retinoids to modify gene transcription . While the retinoids have more traditionally been used to treat cancer and various skin conditions recent data suggests a role in arthritis therapeutics. Specifically, a novel retinoic acid receptor (RAR) antagonist (BMS-189453) reduced MMP-1 expression in synovial fibroblasts. Furthermore, BMS-189453 treatment blocked the clinical progression of arthritis beyond soft tissue inflammation in collagen induced arthritis. In a second model of arthritis BMS-189453 treatment significantly reduced swelling with no notable progression to joint distortion/destruction. As well as reducing MMP-1 expression BMS-189453 also prevented the overexpression of MMP-13 and MMP-3 in arthritic joints. This is the first study to show the clinical potential of RAR antagonists in arthritis. Entry date March, 2003 Adapted from Beehler et al, J Rheumatol 2003 Feb;30(2):355-63
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