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 that may avoid some of the common side effects associated with other medications that curb the immune system. The new drug, CP-690,550, developed by Pfizer researchers, may be of major importance for those who are treated with immunosuppressants for organ transplants or autoimmune diseases.

      In its development and study, 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 decreased 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.

      CP-690,550 is the first Jak3 inhibitor to show positive results in primates. Further animal studies are being conducted to determine whether this drug could be used successfully and safely in humans. The finding that CP-690,550 selectively suppresses the immune response in transplant rejection with minimal toxicity also suggests that a Jak3 inhibitor might be useful in the treatment of autoimmune diseases.

--Source: NIH News, October 30, 2003