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发表于 2003-11-2 19:27
U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
National Institute of Arthritis and
Musculoskeletal and Skin Diseases
http://www.niams.nih.gov/
EMBARGOED FOR RELEASE
Thursday, October 30, 2003
2 p.m. ET
Contact:
Ray Fleming
301-496-8190
[email protected]
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 cells. They
went on to show that the mutation of the gene encoding Jak3
was responsible for a form of severe combined
immunodeficiency (SCID). Because Jak3 is essential for
immune cell function, and because its expression is limited
to blood cells, the team proposed that inhibiting Jak3
might be the basis for a new class of immunosuppressant
drugs. The group then entered into a collaborative research
and development agreement with Pfizer -- a partnership that
has enabled Pfizer to develop this new drug.
CP-690,550 is the first Jak3 inhibitor to show positive
results in primates. Further animal studies are being
conducted to determine if this drug could be used
successfully and safely in humans.
Immunosuppressant drugs, which inhibit the body's immune
response, are given to prevent the body from rejecting
transplanted organs, and are also used to treat autoimmune
diseases such as lupus, rheumatoid arthritis, eczema and
psoriasis. Autoimmune diseases cause the immune system to
attack healthy, normal tissue as if it were a foreign
substance. 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.
The mission of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS), a part of the
Department of Health and Human Services' National
Institutes of Health, is to support research into the
causes, treatment, and prevention of arthritis and
musculoskeletal and skin diseases, the training of basic
and clinical scientists to carry out this research, and the
dissemination of information on research progress in these
diseases. For more information about NIAMS, call the
information clearinghouse at (301) 495-4484 or (877) 22-
NIAMS (free call) or visit the NIAMS Web site at
.
Changelian P, et al. Prevention of organ allograft
rejection by a specific Janus Kinase 3 inhibitor.
"Science", 2003;302:875-878.
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