copper chelation halts restenosis

From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Tue May 27 2003 - 06:21:19 MDT

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    Copper Chelation Is A Promising New Therapy For Clogged Arteries

    Researchers at the Maine Medical Center Research Institute (MMCRI) in
    Scarborough, Maine, announce their discovery that the renarrowing of
    arteries following balloon angioplasty can be halted by copper chelation
    therapy. Preventing the function of copper in the body stops arteries
    from reclogging following the mechanical stress of removing arterial
    obstructions through angioplasty. The therapy works by limiting the
    cellular export of growth factors and cytokines involved in this process.
    "This represents a major contribution to medical science," said Kenneth
    A. Ault, M.D., Director of MMCRI. "This finding could be ready for
    widespread clinical use in humans in a very few years." Thomas Maciag,
    Ph.D. and his team of scientists at MMCRI's Center for Molecular Medicine
    led a team of investigators from the Netherlands and Bulgaria, including
    scientists from Dartmouth Hitchcock Medical Center. They discovered that
    the function of copper is necessary for restenosis, and that after
    angioplasty or stent surgery is performed, the presence of copper in
    cells of the artery enables the regrowth of cells from within the injured
    vessel. This process recloses the artery in about 30% of cases, requiring
    more surgery with its inherent expense and risk to the patient. "Maciag
    and colleagues appear to have solved a long-lingering paradox in the
    field of growth factor biology," commented Dr. Elazer R. Edelman,
    Director of Harvard-MIT Biomedical Engineering Center in Cambridge,
    Massachusetts. "Their imaginative work may provide novel treatment
    modalities for a range of critical diseases."

    This work was published in a preeminent journal, Proceedings of the
    National Academy of Sciences, May 27, 2003, in the paper "Copper
    Chelation Represses the Vascular Response to Injury."
    The scientists at MMCRI found that the commonly available reagent TTM
    (tetrathiomolybdate), which is a specific copper chelator, stopped
    inflammation and growth of the unwanted new tissue responsible for
    narrowing of the arteries. TTM was able to inhibit the intracellular
    function of key regulators of cell growth which normally enable cells to
    respond to stress. Essentially, chelating copper makes the cells stress
    resistant. Understanding the biochemical pathways of cellular response to
    stress or injury may lead to an alternative and inexpensive treatment to
    efficiently manage restenosis in humans. The discovery is the result of
    approximately fifteen years of basic scientific research. The researchers
    found that an easily obtained chemical reagent made a direct and simple
    clinical application suddenly available. The drug TTM is already in use
    for the treatment of another human disease and, interestingly, has very
    few and readily reversible side effects.



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