Known drug may prevent brain damage from cerebral malaria

A drug used to treat patients with diabetes may prevent damage from cerebral malaria and eliminate subsequent neurological deficits, according to a study published on Thursday in PLOS Pathogens.

Researchers with the Toronto General Research Institute in Canada focused on a diabetes drug called rosiglitazone which activates a molecule called PPARɣ and has anti-oxidant and anti-inflammatory properties. When the scientists gave rosiglitazone and antimalarial drugs to mice at the onset of cerebral malaria symptoms, the mice were more likely to survive. In addition, the mice receiving rosiglitazone did not have the brain abnormalities or cognitive defects seen in mice that only received antimalarial drugs.

Cerebral malaria is a serious complication of infection with the malaria parasite that affects approximately one in a thousand children in areas where malaria is common. Many patients with cerebral malaria die and about a third of those who survive have lasting cognitive and neurological disabilities, such as learning disorders and epilepsy.

The researchers found that rosiglitazone was able to protect the integrity of the blood brain barrier in mice and increased the level of anti-oxidant enzymes and neuroprotective factors in the brain.

In a human clinical trial, adult patients with uncomplicated malaria who received antimalarial drugs plus rosiglitazone also experienced an increase in a neuroprotective factor in the brain called brain-derived neurotropic factor, or BDNF.

"Our results demonstrate that rosiglitazone adjunctive therapy resulted in increased survival and protection from long-term cognitive impairments in a mouse model of cerebral malaria," the authors said. "And the clinical trial data suggests that this approved drug, which has an excellent safety profile when taken for limited periods, might also induce such putative protective mechanisms in humans."

The researchers concluded that rosiglitazone should be tested in human patients with cerebral malaria.