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Apoptosis in the treatment of rheumatoid arthritis The American Autoimmune Related Disease Association lists over 50 different autoimmune diseases. Some of these are common such as rheumatoid arthritis which affects about 1% of all populations, women two to three times more often than men. This translates to a total of 5 million sufferers in the major pharmaceutical markets. The market for agents used to treat rheumatoid arthritis totaled $1.6 billion in 2000. According to some analysts, new therapeutic approaches will drive the market for autoimmune disorders such as treat rheumatoid arthritis to grow at a rate of over 15%, to a value of over $21 billion by 2006. 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 is to move towards disease-modifying anti-rheumatic drugs (DMARDs), notably those molecules able to interfere with TNF or IL-1 signaling. There are a number of examples where treatments of rheumatoid arthritis are following the lead of anti-cancer therapies. Two good examples are inhibitors of angiogenesis and also of matrix metaloproteinase inhibitors. In addition, molecules able to stimulate apoptosis are also emerging as treatments of rheumatoid arthritis. This disease is dominated by the presence of macrophages, lymphocytes and synovial fibroblasts, which leads to the destruction of bone and cartilage. The effectiveness of therapies that are directed against TNF or IL-1 has identified macrophages as a crucial target for therapeutic intervention. This may be related to a reduced rate of macrophage apoptosis and hence the identification of pathways involved in macrophage apoptosis and of molecules able to modulate these pathways deserves pharmaceutical attention.
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