new target for autoimmune disease treatment DR3

Discussion in 'Fibromyalgia Main Forum' started by tansy, Jun 20, 2008.

  1. tansy

    tansy New Member

    U.S. Department of Health and Human Services
    National Institute of Arthritis and Musculoskeletal and Skin Diseases
    (NIAMS) <>
    National Institute of Allergy and Infectious Diseases (NIAID))
    Embargoed For Release: Thursday, June 19, 2008, 12:00 pm EDT

    CONTACT: Trish Reynolds, NIAMS, 301-496-8190, <e-mail:
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    Researchers from the National Institute of Arthritis and
    Musculoskeletal and Skin Diseases (NIAMS), a part of the National
    Institutes of Health (NIH), have identified a promising new target
    for autoimmune disease treatment -- a cell-surface receptor called
    DR3. Their research in mice, published on line in the journal
    "Immunity," suggests that blocking this receptor could slow or stop
    the damaging inflammation characteristic of autoimmune diseases,
    potentially without leaving the body vulnerable to serious
    infections, as many current therapies do.

    DR3 is a protein on the surface of cells. It is a member of the tumor
    necrosis factor (TNF) family of receptors, which bind to molecules
    related to TNF, a cell-signaling protein that promotes inflammation.
    Many of today's most potent treatments for inflammatory diseases,
    such as rheumatoid arthritis and psoriasis, interfere with the action
    of TNF, thereby blocking inflammation. Since current anti-TNF
    therapies don't work in all autoimmune diseases, however, the
    researchers turned to the study of DR3, which is a close relative of
    TNFR1, the main receptor for TNF.

    Working with mouse models of asthma and multiple sclerosis, both
    immune system diseases, the researchers found that mice engineered to
    lack DR3 were resistant to those diseases. "The implication is that
    blocking DR3 in mice, and possibly in humans, is a potential therapy
    for these diseases and perhaps others in which the immune system goes
    awry," said Richard Siegel, M.D., Ph.D., a scientist in the NIAMS'
    Immunoregulation Group, who led the research effort.

    While closely related to TNFR1, DR3 is expressed in T cells, a
    different kind of immune cell (a white blood cell that identifies and
    fights infection) than those that express TNFR1, Dr. Siegel said. The
    NIAMS group collaborated with a laboratory in Cardiff, Wales, which
    had generated genetically engineered mice deficient in DR3, as well
    as with a research group at the NIH's National Institute of Allergy
    and Infectious Diseases (NIAID), which has developed mouse models of
    disease with strong T cell components, such as asthma and multiple
    sclerosis. "These findings open up new avenues for therapy of these
    two diseases as well as to other autoimmune diseases in which T cells
    play a role in causing or perpetuating the disease," said Siegel.

    The researchers hope that DR3-blocking agents will be effective anti-
    inflammatory treatments someday. Siegel noted that if they were to be
    used in rheumatic diseases, they would be a complement to strategies
    that block TNF because they hit a different arm of the immune system.
    "It could be potentially synergistic or complementary," he said.

    Of critical importance, the NIAMS scientists found that removing DR3
    did not appear to suppress the immune response or the ability to
    fight infection within the mice -- a problem with many other
    treatments for autoimmune disease. "We could see the effect of DR3
    deficiency in the diseased organ, but when we looked systemically at
    the immune response at other places in the mouse, it was barely
    affected," said Dr. Siegel. The group's findings suggest that DR3-
    blocking agents might be more effective at specifically treating
    autoimmune disease without breaking down the body's defenses against
    infections, a long-sought goal of researchers in the field.

    For more information about the NIAMS' Immunoregulation Group within
    the Autoimmunity Branch of the Intramural Research Program, visit the
    NIAMS Web site at <

    For more information about autoimmune diseases, visit the Medline
    Plus Web site, a service of the NIH's National Library of Medicine,
    at <>

    NIAID is a component of the National Institutes of Health. NIAID
    supports basic and applied research to prevent, diagnose and treat
    infectious diseases such as HIV/AIDS and other sexually transmitted
    infections, influenza, tuberculosis, malaria and illness from
    potential agents of bioterrorism. NIAID also supports research on
    basic immunology, transplantation and immune-related disorders,
    including autoimmune diseases, asthma and allergies. News releases,
    fact sheets and other NIAID-related materials are available on the
    NIAID Web site at <>.

    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 (NIH), 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 <>.

    The National Institutes of Health (NIH) -- The Nation's Medical
    Research Agency -- includes 27 Institutes and Centers and is a
    component of the U.S. Department of Health and Human Services. It is
    the primary federal agency for conducting and supporting basic,
    clinical and translational medical research, and it investigates the
    causes, treatments, and cures for both common and rare diseases. For
    more information about NIH and its programs, visit <>.
    Meylan F, et al. The TNF-family receptor DR3 is essential for diverse
    T cell-mediated inflammatory diseases. "Immunity" 29, 1-11, July 2008.