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Scientists pinpoint flaw, offer new promise for stroke treatment

The best treatment doctors currently have for stroke can accelerate the death of brain cells in addition to dissolving blood clots, researchers report in the journal Nature Medicine. But they also found good news: Another drug currently used to treat patients with severe sepsis counters the harmful effects, offering the possibility that a combination of two already-approved drugs might offer a powerful new stroke treatment that would give doctors a bigger window of time to treat patients.

The work is the result of a longstanding collaboration between scientists at the University of Rochester Medical Center and counterparts at Scripps Research Institute in La Jolla, Calif. The team found that the clot-buster tPA (tissue plasminogen activator) can magnify the harmful effects of stroke in mice and in human cells, and that a compound known as APC (activated protein C) counters the harmful effects.

"TPA has been a great therapy for some patients, but right now it's available to a tiny minority of patients. We hope to extend the window of opportunity that tPA could be given, by protecting the brain against its toxic effects," says Berislav Zlokovic, M.D., Ph.D., the Rochester neuroscientist who led the research thanks to funding from the National Heart, Lung and Blood Institute. "This holds great promise for stroke therapy."

TPA is best known as a clot buster useful for patients who have the most common type of stroke, where a blood clot blocks blood flow to a portion of the brain, cutting off oxygen. The trauma causes more and more brain cells to die as they try to cope with the damage. The result can be a devastating brain injury that incapacitates the person for life.

TPA can prevent the damage by dissolving the clot and restoring the flow of oxygen but the drug must be given to patients within three hours of the onset of stroke symptoms. That's a big reason why just a tiny fraction of patients benefit from the drug: Zlokovic
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
4-Nov-2004


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