Keck School of Medicine physicians have begun a study of a new drug that aims to dissolve blood clots in the legs without the excessive bleeding that may occur with older drugs.

Fred A. Weaver, professor of surgery and chief of vascular surgery at the Keck School, is principal investigator at USC for the phase I clinical trial of alfimeprase, which will be evaluated at six centers nationwide.

By undergoing safety testing at USC, the drug has come full circle: It got its start in the lab of Francis S. Markland Jr., professor of biochemistry and molecular biology at the Keck School.

Current thrombolytic or "clot-busting" drugs such as urokinase and alteplase work to break up clots that can get stuck in a blood vessel and block blood flow; but they also can affect the whole circulatory system-not just the blood clot-so patients may suffer side effects such as bleeding in the brain, Weaver explained.

Alfimeprase, though, attacks clots directly and disintegrates the tangles of a protein called fibrin that provide a scaffold for blood clots. Physicians in the trial deliver alfimeprase through a catheter.

After the drug dissolves the blood clot, it is quickly inactivated and swept away by a common sentry protein that patrols the circulatory system to protect the body. The drug is also believed to work faster than traditional clot-busters.

"This novel agent is very specific to clots," Weaver said. "There's been a desire to create a drug that acts only on thrombus, and this seems promising."

And it all started with snakes.

Alfimeprase is a modified type of fibrolase, an enzyme found in the venom of numerous North American snakes, especially the southern copperhead.

The enzyme quickens the spread of venom components in snakes' prey by breaking bonds in certain proteins.

Markland's team harnessed that chemical power and explored its pharmaceutical value.

Today, Hyseq Pharmaceuticals Inc., based in Sunnyvale, Calif., and Amgen Inc., based in Thousand Oaks, Calif., are developing the drug.

The trial at USC is enrolling patients with peripheral arterial occlusion, a significant cause of amputation in the United States. Because no drugs are currently approved specifically to treat this disease, the U.S. Food and Drug Administration has granted the drug orphan status for this use.