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). This class was initially represented by immunosuppressants such as methotrexate, azathioprine and cyclosporine. However side effect profiles are driving the industry towards novel biologics. Over 150 candidates or marketed products were identified for the treatment of rheumatoid arthritis. These molecules are broken down into COX inhibitors that are used to treat osteoarthritis and rheumatoid arthritis patients; steroids; immunosuppressants; TNF (alpha) blockers; angiogenesis inhibitors; MMP inhibitors; and a group of about 30 other candidates that target miscellaneous immunological targets. The recent development of new COX-2 inhibitors has been a well-publicized success story. Activity relating to the development of DMARDs has also increased sharply; particularly the development of TNF (alpha) blockers and inhibitors of angiogenesis. CD200 is expressed on a subset of T cells, on all CD19-positive B cells, and is upregulated on most activated T cells and has been suggested to bind to a receptor thus regulating myeloid cell activity in a variety of tissues. In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (a model of multiple sclerosis). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis. Canadian researchers have previously shown that the novel immunosuppressant molecule CD200Fc (linking an extracellular domain of CD200 with a murine IgG2a Fc region) can suppress induction of collagen induced arthritis when given to mice from the time of collagen injection. This occurs in concert with a decrease in the serum levels of anti-collagen IgG. However for CD200Fc to be of therapeutic benefit such a response must be observed when dosing is initiated in animals with established disease. The same group has now shown that this is indeed the case and hence this important data supports the use of CD200Fc in the treatment of rheumatoid arthritis. Moreover the immunoregulatory profile of CD200Fc suggests that it may be of use in autoimmune disorders in general. This technology is currently being developed by the Canadian company Transplantation Technologies.

Entry date November, 2002

Adapted from Gorczynski et al, Clin Immunol 2002 Sep;104(3):256-64.

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