Piolitazone shows promise for preventing brain injury from radiation therapy

Jan 10 2007

Researchers at Wake Forest University School of Medicine are the first to report that in animal studies, a common diabetes drug prevents the memory and learning problems that cancer patients often experience after whole-brain radiation treatments.

"These findings offer the promise of improving the quality of life of these patients," said Mike Robbins, Ph.D., senior researcher. "The drug is already prescribed for diabetes and we know the doses that patients can safely take."

Whole-brain radiation is widely used to treat recurrent brain tumors as well as to prevent breast cancer, lung cancer and malignant melanoma from spreading to the brain. About 200,000 people receive the treatment annually, and beginning about a year later, up to one-half develop progressive cognitive impairments that can affect memory, language and abstract reasoning.

In the current issue of the International Journal of Radiation Oncology - Biology - Physics, Robbins and colleagues report that rats receiving the diabetes drug piolitazone (sold under the trade name Actos) before, during and after radiation treatments did not experience cognitive impairment.

The scientists compared whether treatment with Actos for four weeks or for 54 weeks after radiation would be more effective, and found there was not a significant difference.

The study involved young adult rats that received either radiation treatment equal to levels received by humans or a "sham" treatment involving no radiation. Animals in both groups received either a normal diet or a diet containing the diabetes drug.

Cognitive function was assessed a year after the completion of radiation therapy using an object recognition test. Rats receiving radiation exhibited a significant decrease in cognitive function, unless they received the diabetes drug for either four or 54 weeks after radiation.

"This could be easily applied to patients," said Robbins, a professor of radiation biology. "We know the drugs don't promote tumor growth, and in some cases may inhibit it."

Currently, there are no known treatments to prevent cognitive impairments, and Robbins said the aging of the American population makes it imperative to solve the problem.

"Cancer is a disease of old age, so the number of people getting whole-brain radiation will increase," he said.

In essence, radiation causes the cognitive problems because it speeds up the brain's aging process. Recent research suggests that a cause may be chronic inflammation or oxidative stress. Oxidative stress occurs when cells cannot remove free radicals, or structurally unstable cells that can damage healthy cells.

The study by Robbins and colleagues was based on evidence that the diabetes drug pioglitazone prevents inflammation. The drug activates a specific type of peroxisome proliferator-activated receptors (PPARs) that control fat and glucose metabolism, and may be involved in inflammation.

Robbins said because the drug shows promise for preventing cognitive impairment, it may allow doctors to give higher doses of radiation. Currently, while higher doses of radiation have been associated with longer survival, dose is limited because of potential damage to surrounding healthy tissue.