Study Finds Natural Enzyme Dissolves Clots : Treatment May Limit Stroke Disabilities

Stroke victims in the future may benefit from research that shows the potential of using a natural human enzyme to break down blood clots that cause strokes, a report authored by a UC San Diego School of Medicine professor states in today’s Science magazine.

The medical work shows that the enzyme significantly reduced the rate of death and disability in rabbits that were given stroke-inducing blood clots, according to Dr. Justin Zivin, an associate professor of neurosciences at the UCSD Medical School and the principal author of the article. Zivin, who recently joined the UCSD faculty, conducted most of the stroke study while at the University of Massachusetts Medical Center.

While the potential exists for the enzyme to limit disabilities in humans, Zivin said, substantial additional laboratory and animal experiments are required before testing could begin with patients.

Stroke is a leading cause of death in the United States and results from blood clots that lodge in arteries leading to the brain. The clots block the brain from receiving blood, causing brain tissue to die and leading to neurological damage. In a related disease, a clot can form on an artery wall, then break off and travel to a critical body site where it can cause a heart attack.

Currently, stroke treatment focuses on prevention because little can be done to reverse damage once a stroke has occurred, other than physical therapy to improve basic body movement.

The work by Zivin, together with scientists still at the University of Massachusetts, involved treating rabbits with the enzyme within minutes after they were injected with blood clots that caused small strokes.

Of 11 animals immediately receiving the enzyme, 10 showed no neurological damage after being examined at one-day and one-week periods following the injections. Of 12 animals not receiving the enzyme after having strokes induced, only five were normal one day later.

In addition, autopsies of the rabbits--all of which were painlessly killed one week after the experiments--showed no drug-induced hemorrhaging. Many clot-dissolving agents tested over past years have proved unfeasible in treating strokes because they also cause hemorrhaging.

The enzyme is called tissue plasminogen activator (TPA) and occurs naturally in the human body. Blood normally clots to stop bleeding when a break occurs in a blood vessel, and the enzyme activates chemicals to eliminate the clot once the clot has served its purpose in stemming bleeding.

The enzyme can be produced outside the body using genetic engineering. It already has been shown effective in limiting heart damage for patients with coronary artery thrombosis.

Among the additional study required is research determining how quickly the enzyme would have to be administered after a stroke, Zivin said. Researchers must also show conclusively that the enzyme would not cause hemorrhaging.