Temple Viper Knocks Out Aspirin

25. July 2017
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A substance derived from the poison of the temple viper could be employed against circulatory disorders, heart attacks and strokes instead of using antiplatelets. Its special feature: it works, without leading to increased bleeding tendency.

So-called antiplatelets ensure that platelets do not clump together, thus preventing the formation of thrombi. Antiplatelets are employed in addition to medicines for inhibiting blood clotting (anticoagulants), in order to prevent thrombosis and embolism. Antiplatelets are mainly used in the prevention and treatment of heart attacks, stroke and for other circulatory disorders. One serious side effect nevertheless is that, in the instance of injuries, increased and long-lasting bleeding occurs.

A research team led by Tur-Fu Huang of the National Taiwan University In Taipei has now developed a new substance based on snake venom. It prevents clumping of blood platelets into blood clots, without causing prolonged bleeding. The researchers published their results in the journal Arteriosclerosis, Thrombosis And Vascular Biology.

Already in earlier studies the scientists had discovered that a protein called trowaglerix, which derives from the poison of Wagler’s pit viper, or temple viper (Tropidolaemus waglerix), stimulates blood platelets to clump into blood clots. The snake protein latches onto a protein called glycoprotein VI (GPVI) which is located on the surface of the blood platelets. In previous investigations Huang and his team were able to show that blood platelets lacking GPVI do not form blood clots and at the same time do not lead to excessive bleeding. This led the researchers to conclude that the blocking of GPVI could prevent the formation of blood clots without leading to prolonged bleeding.

Substance could be the basis for new medications

In their current study Huang and his team developed a modified molecule based on trowaglerix, which blocks the activity of GPVI and can thus inhibit the clumping of blood platelets. When the new molecule was mixed with blood, no clumping of the blood platelets actually occurred. Furthermore, in experiments with mice the new substance retarded the formation of blood clots and the treated mice no longer had more bleeding than untreated mice.

“Some of the hitherto available thrombocyte aggregation inhibitors act on another protein, the so-called glycoprotein IIb or IIIa”, Huang reports. “These medications are based on another protein which is found in snake venom. Why these substances lead to increased bleeding Is however not fully known”.

The results of the current study suggest that the new molecule could be the basis for the development of new safer substances, using which no increased bleeding occurs. However, the substance needs to be tested in further experiments on animals and subsequently in humans.

Improvement of the active substance and human testing needed

“The type of molecule we have developed usually does not remain in the body very long. Therefore, other techniques have to be developed that ensure that the substance remains in the human body for a longer period of time. This could, for example, be a specific formulation, or a system through which the molecule is targeted”, says Jane Tseng, one of the co-authors of the study.

“In order to avoid unwanted side effects, it also needs to be verified that the molecule interacts only with GPVI, but not with other proteins”. The researchers now want to carry out further studies so as to further improve the design of the molecule and its efficacy and safety.

“Snake venom contains many unique components that affect the interaction between the cells and have an affect on the connective tissue between the cells, the so-called extracellular matrix effect”, Tur-Fu Huang explains.

The research group has since the 1970s been investigating the effects of snake venom on blood coagulation, growth of blood vessels (angiogenesis) and metastasis in tumours. With their experiments, the researchers hope to develop new pharmaceutic agents from the components of the snake venom to hinder the formation of metastases.

The poison from Wagler’s pit viper works primarily by interfering with the mechanisms of blood clotting, therefore leading to thrombosis and embolism. In addition, damage and eventually the death of tissue occurs, first and foremost of muscle tissue. Wagler’s pit viper is widely spread in Southeast Asia and belongs to the viper family. Whereas it normally remains still during the day, it becomes active at dusk and at night.

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