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Snake venom might provide a safer antiplatelet drug

June 08, 2017

DALLAS, June 8, 2017 - Researchers have designed a safer antiplatelet drug based on a snake venom, according to new research in Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Association journal.

Antiplatelet drugs prevent blood cells called platelets from clumping together and forming blood clots and are widely used to treat heart disease. Excessive bleeding after injury is a serious effect of current antiplatelet drugs.

Researchers from the National Taiwan University designed a drug to interact with the protein glycoprotein VI (GPVI) that sits on the surface of platelets.

An earlier study by the team found that trowaglerix, a protein in the venom of the Tropidolaemus waglerix snake, stimulated platelets to form blood clots by latching onto GPVI. Previous studies have shown that platelets missing GPVI do not form blood clots in patients and do not lead to severe bleeding, leading researchers to think that blocking GPVI could prevent blood clotting while avoiding the side effects of prolonged bleeding.

The new study may be the first to design a molecule based on the structure of trowaglerix to block GPVI activity. It prevented platelets from clotting when it was mixed with blood, and 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.

Some of the currently available antiplatelet drugs target another protein, glycoproteins IIb/IIIa. Those drugs were based on another protein found in snake venom - but why that target leads to the bleeding side effect is not fully understood, said lead co-author Tur-Fu Huang, Ph.D., Graduate Institute of Pharmacology at National Taiwan University.

Excessive bleeding after injury is a serious effect of current antiplatelet drugs, so the results support that this molecule design can be a template for a new, safer class of antiplatelet drugs with limited bleeding side effect, according to researchers.

However, the drug needs further testing in animals and then in humans before it can be used in patients.

"In general, this type of molecule design does not last long in the body, so techniques like formulation or delivery system are likely needed to extend the exposure time in the human body," said co-author Jane Tseng, Ph.D., director and professor at Graduate Institute of Biomedical Electronics and Bioinformatics and Drug Research Center at the National Taiwan University. "The design must also be optimized to ensure that the molecule only interacts with GPVI and not other proteins which can cause unintended reactions."

Efforts to improve this molecule's design are underway, Tseng added.
-end-
Other co-authors are Chien-Hsin Chang, Ph.D.; Ching-Hu Chung, Ph.D.; Yi-Shu Tu, Ph.D.; Cheng-Chieh Tsai, M.S.; Chun-Chieh Hsu, Ph.D. and Hui-Chin Peng, Ph.D. Author disclosures are on the manuscript.

The National Science Council of Taiwan supported the study.

Additional Resources:
  • After June 8, view the manuscript online.

  • Follow AHA/ASA news on Twitter @HeartNews

  • For the updates and new science from the Arteriosclerosis, Thrombosis and Vascular Biology journal follow @atvbahajournals

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations and health insurance providers are available at http://www.heart.org/corporatefunding.

About the American Heart Association

The American Heart Association is devoted to saving people from heart disease and stroke - the two leading causes of death in the world. We team with millions of volunteers to fund innovative research, fight for stronger public health policies, and provide lifesaving tools and information to prevent and treat these diseases. The Dallas-based association is the nation's oldest and largest voluntary organization dedicated to fighting heart disease and stroke. To learn more or to get involved, call 1-800-AHA-USA1, visit heart.org or call any of our offices around the country. Follow us on Facebook and Twitter.

American Heart Association

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