Studies of a rare genetic condition that increases cancer risk have unveiled a potential treatment for metabolic syndrome, a common disorder that puts many adults at sharply increased risk of type 2 diabetes.

In findings published in the journal Cell Metabolism, researchers at Washington University School of Medicine in St. Louis report that a small dose of the malaria drug chloroquine eased many symptoms of metabolic syndrome in mice, reducing blood pressure, decreasing hardening and narrowing of the arteries and improving blood sugar tolerance.

"We already know that chloroquine is safe and well-tolerated, and our mouse results suggest we may only need very low and perhaps infrequent doses to achieve similar effects in humans," said lead researcher Dr. Clay F. Semenkovich.

The surprising chain of connections that led to the possibility of using chloroquine also has provided a fairly detailed sense for how the drug may be helping.

That chain starts with a link between insulin and a protein known as ATM. Normally involved in the response to stress and repair of DNA, ATM is mutated in the rare genetic disorder ataxia-telangiectasia (AT). Individuals with this disease have markedly increased risk of tumors, immunological problems and severe progressive deterioration of a part of their brain that controls muscle function and coordination.

In the present study, researchers demonstrated that the ATM enzyme is important for many of the beneficial effects of insulin and that loss of ATM worsens blood sugar control, high blood pressure and atherosclerosis.

The researchers found reduced ATM levels created a condition like metabolic syndrome in mice fed a high-fat diet and given a genetic predisposition to heart disease.

Symptoms included increased insulin resistance and atherosclerosis and higher levels of a signaling molecule that activates a class of immune defensive cells known as macrophages.

At low doses, chloroquine moderated many of the symptoms of metabolic syndrome in several mouse models of metabolic syndrome and type 2 diabetes. Researchers are still determining the exact details of how chloroquine and insulin signal through ATM, and those details could lead to additional treatment options for these disorders.

A pilot clinical trial at Washington University using low dose chloroquine in patients with symptoms of metabolic syndrome is showing promising results.

"We want to make sure we find the right dose—it may be possible to go even lower—and that it's safe and effective," Semenkovich says.