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EPFL develops the first synthetic inhibitor for artificial lungs

In a study led by EPFL, scientists have developed a synthetic blood-thinner that, unlike all others, doesn’t cause bleeding side-effects. The highly potent, highly selective, and highly stable molecule can suppress thrombosis while letting blood clot normally following injury.

Blood Thinner Enzyme
A FXII inhibitor cyclic peptide blood-thinner. | Copyright iStock – C. Heinis

Patients who suffer from thrombosis, pulmonary embolism or stroke are usually put on drugs that help their blood flow more smoothly through their body. Blood thinners can keep blood clots from forming or getting bigger, and can therefore help with recover from heart defects or prevent further complications.

However, they work by blocking enzymes that help to stop bleeding after an injury. Because of this, virtually every blood thinner available today can lead to serious, and even life-threatening bleeding following an injury.

An enzyme called “coagulation factor XII” (FXII) was discovered a few years ago, following a study showing that mice without the enzyme had a very reduced risk of thrombosis without having bleeding side-effects.

Today, the Laboratory of Therapeutic Proteins and Peptides of Professor Christian Heinis at EPFL has developed the first synthetic inhibitor of FXII. The inhibitor has high potency, high selectivity, and is highly stable, with a plasma half-life of over 120 hours.

With a potent FXII inhibitor in hand, Heinis’s group wanted to evaluate it in actual disease models. To do this, they teamed up with experts in blood and disease-modeling at the University Hospital of Bern (Inselspital) and the University of Bern. This collaboration between institutions from the cantons of Vaud and Bern showed that the inhibitor efficiently blocks coagulation in a thrombosis model without increasing the bleeding risk.

“The new FXII inhibitor is a promising candidate for safe thromboprotection in artificial lungs, which are used to bridge the time between lung failure and lung transplantation,” concludes Heinis.

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