Experimental Drug May Extend Therapeutic Window

Photo: Experiment

The research suggests that the
experimental drug may protect
against neurological maladies;
© panthermedia.net/Sergey

Stroke, which occurs when blood flow to a part of the brain stops, is the No. 4 cause of death and the leading cause of adult disability in the United States. According to the American Stroke Association, the Food and Drug Administration-approved tPA (tissue plasminogen activator) is the best treatment for stroke caused by a blocked artery, but to be effective, it must be administered within three hours after symptoms start. If given outside that three-hour window, tPA has shown serious side effects in animal and human brains, including bleeding and breakdown of the brain's protective barrier.

Generally, according to the American Stroke Association, only 3 to 5 per cent of those who suffer a stroke reach the hospital in time to be considered for tPA treatment.

"What tPA does best is to break down clots in the blood vessel and restore blood flow, but it is a powerful enzyme," said Doctor Berislav V. Zlokovic. "After three hours, tPA also damages the blood vessel and causes intracerebral bleeding. We have developed something that not only counteracts the bleeding but also reduces brain damage and significantly improves behavior after stroke. I feel very strongly that this approach will extend the therapeutic window for tPA."

Zlokovic and his team gave tPA — alone and in combination with 3K3A-APC — to mice and rats four hours after stroke. They also gave 3K3A-APC for three consecutive days after stroke. They measured the amount of brain damage, bleeding and motor ability of the rodents up to seven days afterward.

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.

Previous research suggests that the experimental drug may also protect against other neurological maladies such as amyotrophic lateral sclerosis and traumatic brain injury as a standalone therapy.

MEDICA.de; Source: University of Southern California (USC)