Snake venom inspires effective factor Xa reversal agent

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Snake venomA study has shown modified human factor X to be a safe and effective reversal agent for prevention and treatment of bleeding in patients taking factor Xa oral anticoagulants. This new therapeutic factor X was inspired by a snake venom protein.

Published in Nature Communications, the study was performed by a group of leading haemostasis and thrombosis researchers at the Leiden University Medical Centre (LUMC; Leiden, The Netherlands). Research and development was led by professor Pieter Reitsma.

The new factor X is the lead product in development of VarmX, a pharmaceutical LUMC spin-off.

To avoid spontaneous stroke or deep vein thrombosis, millions of cardiac patients worldwide daily take synthetic factor Xa anticoagulants, such as apixaban, edoxaban or rivaroxaban.

As yet there is no agent to stop the effect of these anticoagulants. This is a significant unmet medical need for patients experiencing severe internal bleeding or requiring emergency surgery.

Today, when a patient requires emergency surgery, doctors have to wait for the medication to clear. Patients might otherwise suffer from severe bleeding.

Increasing use of factor Xa inhibitors for anti-coagulation has lead to global demand for a compound such as PseudoXa is growing rapidly.

Snake venom

A snake venom protein of the most venomous snake in the world—the Australian brown snake—was the researcher’s source of inspiration. The responsible protein in the snake venom causes blood to clot, but differs from that of a human being. Identifying the part of the snake’s coagulation protein that differed, the researchers applied this to the human version.

Reitsma explains, “The altered human protein did exactly what it had to do. In the laboratory, our researchers observed that the protein did cause the blood to coagulate, but did not react to the blood thinners. This bypasses the effect of blood thinners. This is ideal when a patient who takes blood thinners requires emergency surgery.

“Innovative research into the properties of this snake’s venom provided the scientific basis for the factor Xa reversal agent. This is exemplary of the translation of basic research into a potential life-saving therapy.”

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