Mark of the vampire
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.
As with all clinical trials, an outside panel also independently monitors patient safety. When the study coordinators recently suspended recruitment into the trial, they did so at the recommendation of this panel, which requested additional safety data before the trial could proceed but did not specify the nature of the issue.
These kinds of announcements, although potentially serious, happen with some frequency, Liebeskind says. “This could perhaps be as mild and benign as a housekeeping issue,” he says -- if, for example, one of the study sites failed to deliver its completed data on time. “Of course,” he adds, “there is also the possibility that there’s a more serious safety issue.”
In an earlier trial, researchers studied dosages of desmoteplase administered in 94 patients three to nine hours after the stroke’s onset. A high dose of desmoteplase sufficiently increased blood flow to the brain in 62% of patients, as compared with 24% who received no medication. Sixty percent of those treated with a high dose showed an improvement in clinical outcomes such as cognition and motor control, compared with 23% in the placebo group.
Only one out of 59 patients who received the drug suffered brain-bleeding side effects.
Scientists in Germany are also performing animal studies to investigate desmoteplase for use in hemorrhagic stroke, caused by bleeding within the brain. And desmoteplase could soon be studied to treat other health problems related to blood clots, researchers say, such as heart attacks, deep vein thrombosis or pulmonary embolism.
A cure for vampirism, however, might have to wait a couple more years.
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Of spiders and stitches and more
Vampire bats aren’t the only ghoulish creatures carrying around potential health treats. Now researchers are eyeing spider webs for a tricky new biomaterial that could be used in various medical applications.
How it’s made: A typical spider spins six different kinds of silk, says Randy Lewis, professor of molecular biology at the University of Wyoming. Some silks get woven into specific patterns for a web; other kinds become a death shroud for trapped insects. All are bouncy and super-tough. “Typical spider silk is actually five times stronger than steel,” Lewis says.
He and his team have genetically engineered bacteria with synthetic spider silk genes. The bacteria can make spider silk proteins on demand, with varying degrees of strength and elasticity. Lewis collects the protein fibers and then spins his own spider silk in the lab. One Canadian company, Nexia Biotechnologies Inc.'s BioSteel, has also tested other large-scale production mechanisms -- in the mammary glands of goats.
Where it might go: With mass production, spider silk would make excellent surgical suture material, Lewis says. The threads could be as strong as current materials, but up to 10 times thinner. Tiny stitches would be a boon for fields such as eye surgery, neurosurgery or plastic surgery. And unlike silkworm silk and other materials, spider silk doesn’t trigger an immune response in the body.
Toughness and flexibility also make spider silk a natural possibility for artificial ligaments. No good alternatives for ligaments or tendons are available, Lewis says.
In the far future, he envisions even more nifty orthopedic scenarios. Spider silk could function as a temporary replacement ligament in the knee while serving as a scaffold on which stem cells would grow -- and as the cells matured, the natural ligament could slowly take over from the spider silk ligament until the regenerated knee ligament was fully grown.
The same bouncy qualities that allow spider webs to catch high-flying insects without snapping might also make the silk useful in other situations: in automobile air bags. Air bags blow passengers back into the seat with explosive force, Lewis says, but silk air bags might be able to absorb more energy. This could reduce air bag injuries and even make them safe for use with infants in car seats.
Why it’s taking so long: “It’s very difficult to get spider silk,” Lewis says. His team had to resort to surgery during recent studies -- anesthetizing the spiders and extracting their silk fibers, one spider at a time. In England and France in the 19th century, ambitious researchers tried other methods, he says. They copied the industry’s techniques for silkworm cultivation and attempted to breed lots of spiders in close quarters. “But spiders aren’t like silkworms,” Lewis says. “Spiders aren’t sociable. They just tended to kill each other.”