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NIAMS researchers collaborate to produce targeted immunosuppressant drug

Investigators at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Pfizer Global Research and Development and Stanford University have collaborated in studying a new immunosuppressant drug, CP-690,550, that may avoid some of the common side effects associated with other medications that curb the immune system. The new drug, discovered by Pfizer researchers, may be of major importance for those who are treated with immunosuppressants for organ transplants or autoimmune diseases.

John O'Shea, M.D., Yong-Jie Zhou, M.D., and their team in the NIAMS Molecular Immunology and Inflammation Branch joined scientists from Pfizer and Stanford in developing and studying the drug. CP-690,550 was tested in mice with heart transplants and in monkeys with kidney transplants done by Stanford. In both cases, animals treated with CP-690,550 survived much longer than untreated animals. None of the treated animals showed signs of such immunosuppressant side effects as increased cholesterol, blood sugar, blood pressure or increased white blood cell count. The animals also showed no significant decreases in white blood cells or platelets.

The new drug, reported in the journal Science, inhibits the enzyme Jak3, a protein discovered by the NIAMS team in 1994 that is found only in immune system cells. The new study shows that inhibiting this enzyme has the effect of suppressing the immune system, while not affecting other systems of the body. Current immunosuppressant drugs target enzymes found in cells throughout the body, resulting in the toxic side effects. The Jak3 inhibitor has the advantage of selectively targeting a protein that only has effects on immune cells.

The finding culminates a long process of research and discovery by the NIAMS team. After discovering Jak3, the team demonstrated that this protein, called a kinase, was critical for the cell signaling process resulting in the development of infection-fighting white blood
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Contact: Ray Fleming
flemingr@mail.nih.gov
301-496-8190
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
30-Oct-2003


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