A drug used for decades to treat and prevent malaria might also fight the many symptoms of metabolic syndrome, a potentially disabling condition that is estimated to affect as many as a quarter of American adults. The findings appear in the November 2006 issue of the journal Cell Metabolism, published by Cell Press.

Researchers, led by Clay F. Semenkovich of Washington University School of Medicine and Michael B. Kastan of St. Jude Children's Research Hospital, found in studies of mice that the antimalaria drug chloroquine improved symptoms of metabolic syndrome; the drug reduced atherosclerosis, lowered blood pressure, and improved blood sugar tolerance. Chloroquine works by activating a particular stress pathway that mediates susceptibility to the syndrome, they found.

"In animals, activating this pathway with extremely low doses of chloroquine counteracted many of the features of metabolic syndrome," said Semenkovich. Semenkovich said he expects to begin a clinical trial of the drug's utility for curbing metabolic syndrome in human patients very soon.

Often associated with insulin resistance, metabolic syndrome can include five components: high triglycerides, low "good" cholesterol, high blood pressure, high blood sugar, and central obesity--characterized in men by a pants waist size of 40 or greater, Semenkovich said. Patients who exhibit three of the five components fit the criteria for metabolic syndrome.

The condition is also associated with atherosclerosis, leaving patients at increased risk of death from cardiovascular disease, the researchers said.

Rather than representing "a unique entity," some have suggested that the metabolic syndrome may simply reflect the cumulative contribution of its components to atherosclerotic risk, the researchers said. An alternative view is that atherosclerosis, insulin resistance, and the component clinical features of the metabolic syndrome share a common unifying mechanism, t
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
7-Nov-2006