A synthetic blood-thinner has been recently developed to help patients suffering from stroke or thrombosis pulmonary embolism. This blood-thinner can help the blood to flow through the blood without any bleeding side-effects. This highly-effective and stable molecule can prevent blood clots from developing or becoming bigger. It can also help patients who suffer heart defects to recover fully.
However, the regular blood-thinner block enzymes that are responsible for stopping bleeding after an injury. As a result of this, regular blood thinners can cause severe bleeding after sustaining an injury. This problem continued for a long time until a study carried out a few years ago revealed that a blood thinner with no bleeding side-effects can be developed.
In this study, mice that were genetically altered to have a deficiency in an enzyme responsible for blood clotting were used. This enzyme is known as “coagulation factor XII.” The mice lacking this enzyme had a lower risk of thrombosis without any bleeding side-effects. This discovery resulted in a search for FXII inhibitors.
A synthetic inhibitor finally discovered
The Laboratory of Therapeutic Proteins and Peptides at EPFL finally developed a synthetic inhibitor of FXII. This higly effective, highly stable, and highly selective inhibitor has a plasma half-life of more than 120 hours. This study was the result of a partnership with other laboratories in the US and Switzerland.
The FXII inhibitor is a variation of a cyclic peptide that we identified in a pool of more than a billion different peptides, using a technique named phage display.Heinis
The inhibitor was improved by using synthetic amino acids to replace many of its natural amino acids. However, it wasn’t an easy task as it took some years and several Ph.D. students and post-docs to accomplish this.
Having an effective FXII inhibitor, Heinis’s group desired to assess it in actual disease models. To get this done, they partnered with professionals in the University Hospital of Bern (Inselspital), the blood and disease-modeling department.
Having worked with Professor Anne Angelillo-Scherrer’s group, it was revealed that the inhibitor closes up coagulation without increasing the risk of bleeding.
The new FXII inhibitor is a promising candidate for safe thrombo protection in artificial lungs, which are used to bridge the time between lung failure and lung transplantation. In these devices, contact of blood proteins with artificial surfaces such as the membrane of the oxygenator or tubing can cause blood clotting.Heinis
The major problem here is that the inhibitor has a short retention time, it is very small and can be filtered out by the kidney.
We’re fixing this; we’re currently engineering variants of the FXII inhibitor with longer retention time.Heinis