therapeutic window

Drug may limit brain damage after stroke

An experimental drug appears to reduce brain damage, eliminate brain hemorrhaging, and improve motor skills in older stroke-afflicted mice.

The drug appears to have the same effect in stroke-afflicted rats with comorbid conditions such as hypertension, researchers say.

A new study provides additional evidence that the drug, 3K3A-APC, may be used as a therapy for stroke in humans, either alone or in combination with the FDA-approved clot-busting drug therapy tPA (tissue plasminogen activator).

Clinical trials to test the drug’s efficacy in people experiencing acute ischemic stroke are expected to begin recruiting patients in the US in 2014.

“Currently, tPA is the best treatment for stroke caused by a blocked artery, but it must be administered within three hours after stroke onset to be effective,” says Berislav V. Zlokovic, director of the Zilkha Neurogenetic Institute (ZNI) at the University of Southern California Keck School of Medicine.

Keeping the window open

“Because of this limited window, only a small fraction of those who suffer a stroke reach the hospital in time to be considered for tPA. Our studies show that 3K3A-APC extends tPA’s therapeutic window and counteracts tPA’s tendency to induce bleeding in the brains of animals having a stroke.”

The drug is a genetically engineered variant of the naturally occurring activated protein C (APC), which plays a role in the regulation of blood clotting and inflammation. 3K3A-APC has been shown to have a protective effect on the lining of blood vessels in rodent brains, which appears to help prevent bleeding caused by tPA.

For the study, published in the journal Stroke, researchers gave tPA—alone and in combination with 3K3A-APC—to mature female mice and male hypertensive rats four hours after stroke.

They also gave 3K3A-APC in regular intervals up to seven days after stroke. They measured the amount of brain damage, bleeding, and motor ability of the rodents up to four weeks after stroke.

The researchers found that, under those conditions, tPA therapy alone caused bleeding in the brain and did not reduce brain damage or improve motor ability when compared to the control.

The combination of tPA and 3K3A-APC, however, reduced brain damage by more than half, eliminated tPA-induced bleeding and significantly improved motor ability.

Zlokovic’s team previously reported similar results in young, healthy male rodents.  A Phase 1 trial testing the safety of 3K3A-APC in healthy human volunteers concluded in February.

Zlokovic is the scientific founder of ZZ Biotech, a Houston-based biotechnology company he co-founded with USC benefactor Selim Zilkha to develop biological treatments for stroke and other neurological ailments.

Source: University of Southern California

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