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MEDICINE | IN THE LAB

Mark of the vampire

The saliva of a bat species has an enzyme that may help prevent brain damage in more stroke victims. A new drug holds promise.

October 30, 2006|Regina Nuzzo | Special to The Times

JUST for the record, vampire bats don't suck. They lap.

Under the cover of darkness, the mouse-sized Desmodus rotundus flies out from rocky caves to find a sleeping horse or cow. Its razor-sharp incisors carve out a tidy crater of flesh, no bigger than a Halloween M&M, usually without waking its prey.

Then, perched over the welling wound, the vampire bat laps up about a tablespoon of blood -- its sole source of nourishment -- with a delicate, bright-pink tongue.

Normally, wounds like these would start to heal within minutes. But dinnertime for a vampire bat lasts as long as half an hour. Its saliva contains a special enzyme that immediately liquefies blood clots, keeping the vampire bat's meal smooth and fresh.

The same problem facing vampire bats -- the need to keep blood vessels clot-free -- also faces cardiovascular researchers. Now some of them are hoping the enzyme that allows vampire bats to avoid feeding on mouthfuls of coagulated blood might also help prevent brain damage in stroke victims.

Since last year, clinical trials have been underway to test the effectiveness of a genetically engineered, bat-saliva enzyme in a new clot-busting drug to be used for emergency treatment of ischemic stroke, in which blood supply to the brain is cut off. If approved, the drug would allow doctors to treat patients up to nine hours after symptoms begin, extending the current three-hour limit for stroke medication.

Earlier studies in humans and animals have found the drug, called desmoteplase, to be safe and accompanied by fewer side effects than existing treatments. The hope is that desmoteplase acts to dissolve only the clotted area blocking blood flow to the brain and causing stroke -- thus leaving fragile blood vessels in the brain intact.

Although researchers are still hopeful about desmoteplase, more information is needed about its safety. On Wednesday, the study's coordinators announced that they were temporarily halting enrollment of new patients to allow time for more patient safety data to be analyzed.

In 2004, the Food and Drug Administration granted desmoteplase's developers, Paion in Germany and Forest Laboratories Inc. in New York, a fast-track application. These applications aim to speed the development process of products addressing unmet medical needs.

About 700,000 people suffer a stroke every year in the United States, according to the American Stroke Assn., and about 1 in 5 of them die within a month. Untreated, a stroke lasts about 10 hours and kills 1.9 million brain cells every minute -- usually resulting in a region of dead brain tissue bigger than a ping-pong ball.

Quick treatment of stroke is crucial, says Dr. David S. Liebeskind, associate neurology director at UCLA Stroke Center and a researcher in the desmoteplase trial. "Every minute counts," he says. "It can make the difference not just between life and death but also between an independent life or a dependent, disabled life for many years thereafter."

The only FDA-approved medication for ischemic stroke -- alteplase (Activase) -- is currently limited to a three-hour window immediately after a stroke. Yet only about 3% of stroke victims arrive at the hospital within three hours, says Dr. Andrew Slivka, neurology professor at the Ohio State University Medical Center and a researcher in the trial.

"That really limits the number of patients that we can even treat," he says.

Alteplase is the genetically engineered form of a compound called tissue plasminogen activator, or tPA, a clot-dissolving enzyme naturally found in humans and other mammals. But tPA isn't perfect: It can sometimes cause bleeding in the brain, especially when treating stroke after too much time has passed, says Dr. Wolfgang Sohngen, co-founder and chief executive of Paion.

Vampire bat saliva, on the other hand, has been "super-optimized by evolution" to do a clot-busting job, Sohngen says. "If vampire bats were not good at feeding on blood, they would have disappeared, " he says. "The enzyme's only job is to break up clots."

Desmoteplase works by switching on special protein-eating enzymes in the blood called plasmins. When activated, plasmins digest the fibrous protein mesh that forms the core of blood clots. Blood can then reach the brain again.

Eighty centers in Europe, Australia, Canada and the United States, including UCLA, are participating in the phase 3 randomized clinical trial, which has been expected to end in early 2007. Researchers hope to enroll a total of 186 patients who arrive at the hospital three to nine hours after stroke onset.

Each patient enrolled in the study is closely monitored for brain hemorrhaging and other side effects. Three months after treatment, the researchers assess how well the patient's damaged brain regions have recovered.

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