Snake charms researchers with possibilities of blood clot prevention

The lethal venom of a Southeast Asian pit viper is being considered to help create a new class of antiplatelet drugs that could prevent dangerous blood clots.

Researchers from the National Taiwan University found that a protein isolated from the venom of the Wagler's pit viper interacted with a glycoprotein receptor on blood platelets to limit blood clots in mice - without severe bleeding.

A protein from the venom could be used to create a new type of antiplatelet drug, which is prescribed to prevent blood clots in people who have had a heart attack, stroke, bypass surgery or a stent procedure. Current medications work by preventing platelets from participating in blood clot formation, but come with a bleeding risk. Aspirin is the most common that is used.

"Bleeding remains a major barrier to optimal therapy for antiplatelet drugs," said Dr. Richard C. Becker, M.D., professor of medicine at the University of Cincinnati Medical Center and director of the University of Cincinnati Heart, Lung & Vascular Institute in Ohio.

Serious bleeding can occur in 1.5 to 2 percent or more of patients who use antiplatelet drugs, Becker said. Fatal bleeding is much less common at less than 1 percent.

Meanwhile, the research on snake venom, published recently in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, showed success.

The chemical component, trowaglerix, derived from the venom protein helped limit clotting more safely - no severe bleeding, said the study's lead author Tur-Fu Huang, Ph.D., of the Graduate Institute of Pharmacology at National Taiwan University.

The research showed that mice administered this new drug had slower blood clot formation compared to untreated mice. In addition, the treated mice did not bleed longer than untreated mice.

Wagler's pit viper snakes wouldn't be milked to get the venom if a drug is approved. Venom toxins can be synthetically produced based on their chemical blueprint.

It "does not require rounding up all the venomous snakes on earth," Becker said.

"The venom itself will not be used, rather the peptides isolated from the venom could be employed as a 'blueprint' for drug development," he said.

The Wagler's pit viper is a beautifully colored tree-dweller ranging from 20 inches to 3 feet long that is found from Vietnam to Indonesia.

Trowaglerix may join other reptile venom toxins that have made their way into the medicine cabinet.

"There are over 150,000 different species of venomous animals on Earth, such as insects, spiders, jellyfish, scorpions and snakes. Together, they have more than a 20 million-strong toxin arsenal, nearly all of them unknown to science," said Zoltan Takacs, Ph.D., pharmacologist with biotech startup ToxinTech.

The toxins target essential bodily functions, such as nerve-to-muscle communication, blood circulation and coagulation. Death comes from respiratory paralysis or stop of blood circulation, he said.

"In small dose, a pure toxin or its chemical mimetic derived from a deadly venom can be used as a blockbuster lifesaver, such as eptifibatide or captopril," said Takacs. Both drugs were courtesy of snake venom.

The pigmy rattlesnake venom provided the blueprint for eptifibatide, an antiplatelet medication. It's been used since 1998 to treat heart attacks or used in patients undergoing procedures to open blocked blood vessels to the heart.

Captopril was derived from the venom from the Brazilian pit viper. It was the first ACE inhibitor, a drug approved in 1981 to treat high blood pressure, heart failure and heart attack.

"Many drugs developed for the prevention and treatment of cardiovascular disease were initially identified in plants, tree bark and living species on land and in the sea," Becker said. "This is basic chemistry, human curiosity and nature collectively at their best."

It's too soon to tell how well a drug based on these studies will do in humans, he said.

A drug based on the findings could take up to eight years to be approved, although researchers hope for a faster process, Huang said.