X-Message-Number: 21811
Date: Tue, 27 May 2003 05:20:23 -0700 (PDT)
From: Doug Skrecky <>
Subject: copper chelation halts restenosis

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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