Malaria Drug May Fight Metabolic Syndrome

Chloroquine is giving clues to the group of risk factors that harm the heart

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By Amanda Gardner
HealthDay Reporter

TUESDAY, Nov. 7, 2006 (HealthDay News) -- A drug that has been used for decades to treat malaria may also fight the constellation of cardiovascular risk factors known as the metabolic syndrome.

When given in low doses, the drug chloroquine arrested the symptoms of metabolic syndrome in mice and also in a small study involving humans, say researchers reporting the finding in the November issue of Cell Metabolism.

"It's very important that we not say that chloroquine is a cure for anything, although this is much more developed than many other things," stressed Dr. Clay Semenkovich, senior author of the study and professor of medicine at Washington University School of Medicine in St. Louis. He said the finding, "provides an example of how sometimes studying an extremely rare disease may provide unexpected insights into health issues that affect more people."

As many as a quarter of American adults have metabolic syndrome, a collection of health risks that includes excess fat in the abdomen (central obesity), low blood levels of "good" cholesterol, high blood pressure, high triglycerides and high blood sugar. Individuals with at least three of these components are thought to have metabolic syndrome.

The condition is strongly associated with atherosclerosis or hardening of the arteries and is a powerful risk factor for developing diabetes and for dying young of heart disease.

"We don't understand very much about metabolic syndrome, which is extremely common," Semenkovich said. "The different conditions tend to track together and, up to now, there hasn't been a clear way to unify those seemingly disparate problems."

Scientists have been unclear as to whether each of the five components contributes to risk for atherosclerosis, or if there is another factor, such as insulin resistance, that links them together.

Part of the answer has come from an unlikely source.

It has long been known that children with a rare genetic disease called ataxia telangiectasia can develop an unusual form of diabetes. The disease is caused by the ATM (Ataxia Telangiectasia Mutated) gene. People with a copy of the mutant gene are also at increased risk for vascular disease.

ATM could be the unifying link, the experts say.

"We think there's strong evidence that this provides the genetic explanation that could unify seemingly disparate things that lead to metabolic syndrome," Semenkovich said.

When Semenkovich and his colleagues fed mice that were missing one of these genes high-fat diets, the mice developed many of the characteristics of metabolic syndrome.

Even more exciting, however, was that treatment with low doses of the anti-malaria drug chloroquine improved the symptoms of metabolic syndrome and reduced atherosclerosis.

Chloroquine has been shown in laboratory studies to make ATM genes more active. The drug is also used to treat chronic inflammatory conditions such as rheumatoid arthritis and lupus. Many experts think of metabolic syndrome as a chronic inflammatory condition.

The drug also showed promising results when given in low doses to people with metabolic syndrome, Semenkovich said. The team is about to start a clinical trial, funded by the U.S. National Institutes of Health, to look at low doses of chloroquine in humans affected by the condition.

"The ability of anti-malarial drugs like chloroquine to improve insulin action has been appreciated for over two decades," noted Dr. Robert Eckel, professor of medicine at the University of Colorado Health Sciences Center in Denver and past president of the American Heart Association. Until now, however, the mechanism had been attributed to a different mechanism, he said.

Eckel stressed that the St. Louis findings are preliminary and that "the clinical utility and safety of this class of drugs remains to be demonstrated."

Semenkovich agreed. "This does not mean that people should run off to the doctor and ask to be treated with chloroquine for metabolic syndrome, but it does raise important issues," he said. "This may be one of the first ways to provide a unified explanation for something that appears to be affecting a large population."

Current treatments for metabolic syndrome are limited to therapies that seek to control individual components, such as high blood pressure.

More information

There's more on metabolic syndrome at the American Heart Association.

SOURCES: Clay F. Semenkovich, M.D., professor, medicine, Washington University School of Medicine, St. Louis; Robert Eckel, M.D., professor, medicine, University of Colorado Health Sciences Center, Denver, and past president, American Heart Association; November 2006, Cell Metabolism

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