Malaria drug may prevent or delay atherosclerosis

School of Medicine researchers want to see whether it’s possible to reduce the progression of atherosclerosis in healthy people by giving low doses of the malaria drug chloroquine. They are seeking volunteers who are slightly overweight or who have elevated blood pressure.

The human study follows a mouse study that found chloroquine could blunt the progression of plaque buildup in mice that had a genetic predisposition to atherosclerosis.

Janet McGill

“Vascular events such as heart attack and stroke are the biggest health risk facing Americans today,” said Janet B. McGill, M.D., associate professor of medicine in the Division of Endocrinology, Metabolism and Lipid Research. “Healthy adults with modest elevations in blood pressure or cholesterol or with an abundant waistline are often at higher-than-normal risk due to the silent buildup of atherosclerotic plaque in their arteries. That’s an indicator of higher risk for vascular events in the future.”

McGill is looking for healthy adults between 18 and 70 years old with some of those risk factors to participate in a National Institutes of Health-funded clinical trial. They’ll receive a low dose of chloroquine or an inactive placebo for one year. At the start of the study and again after drug therapy, McGill and her colleagues will conduct an ultrasound test on the carotid blood vessel and an MRI to examine the thickness of the vessels.

“In people at risk, we would expect to see a very slight thickening of these vessels,” said Clay F. Semenkovich, M.D., the Herbert S. Gasser Professor and chief of the Division of Endocrinology, Metabolism and Lipid Research. “We want to learn whether chloroquine can slow that thickening.”

Semenkovich and colleagues at St. Jude Hospital for Children in Memphis, Tenn., found that a small dose of chloroquine given to mice reduced blood pressure, decreased hardening and narrowing of the arteries and improved glucose tolerance. Those mice had been genetically engineered without a gene that makes an enzyme called ATM (ataxia telangiectasia mutated). Children without the gene develop a serious disorder called ataxia telangiectasia. In addition to many other problems, children with AT develop an unusual type of diabetes.

Mice without ATM develop atherosclerosis, but when Semenkovich and his colleagues at St. Jude treated the mice with chloroquine, they no longer got atherosclerosis.

“This is an early proof-of-concept study,” she said. “If the concept works, we can then figure out the best doses of chloroquine and someday conduct a long-term study where we don’t just use ultrasounds to look at the thickness of blood vessels but actually follow people to see whether they have fewer heart attacks and strokes following chloroquine therapy.”

The study, called the Atheroma Reduction with Chloroquine in the Metabolic Syndrome (ARCH-MS) study, will screen healthy adults to find those with mildly elevated blood glucose, blood pressure or triglycerides. In addition to ultrasound and MRI tests, some blood tests will be performed, and those who complete the one-year study and two-year follow-up visit will be eligible for up to $1,000 in compensation. Tests and study-related medications are provided free of charge.

For more information about the study, call 362-8681 or contact study coordinator Stacy Hurst at 747-3294 or