For Release: May 28, 2003

Contact: DMS Communications (603) 650-1492

Copper Chelation Holds Promise for Clogged Arteries, Team Finds

HANOVER, NH - Dartmouth cardiologists are part of an international team who discovered that blocking the function of copper prevents artery renarrowing. Copper chelation therapy can halt renarrowing of arteries following balloon angioplasty, announced the researchers, led by Maine Medical Center Research Institute (MMCRI) in Scarborough, Maine.

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 the response to injury.

Chelation refers to the chemical formation of a complex that traps the metal. Essentially, chelating copper makes the cells stress resistant.

Dr. Thomas Maciag and his colleagues at MMCRI's Center for Molecular Medicine led a team that included Dr. Michael Simons, Dartmouth Medical School professor of medicine and of pharmacology and toxicology and Dartmouth-Hitchcock Medical Center chief of cardiology, and Dr. Ebo D. deMuinck, DMS assistant professor of medicine and of physiology, as well as investigators from the Netherlands and Bulgaria. The study is published in the May 27 Proceedings of the National Academy of Sciences.

Copper is necessary for restenosis, and 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, the team discovered. This process recloses the artery in about 30 percent of cases, requiring more surgery with its inherent expense and risk to the patient.

Dr. Elazer R. Edelman, Director of the Harvard-MIT Biomedical Engineering Center said that the team " appear to have solved a long-lingering paradox in the field of growth factor biology. Their imaginative work may provide novel treatment modalities for a range of critical diseases."

The scientists 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. 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 15 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.