PORTLAND, Ore. A team of researchers at Oregon Health & Science University and Washington University in St. Louis have described for the first time the mechanism that gives a mutant enzyme molecule that they have engineered and patented the potential to become a breakthrough drug for treating heart attacks and strokes.
The team described how their genetically modified enzyme, called WE-thrombin, functions as a potent clot busting agent while retaining little of the power that thrombin, its non-engineered parent, has to cause the opposite result, a cascade of clot building. They did so in a paper published recently in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a peer-reviewed journal of the American Heart Association. An editorial commentary in ATVB hailed this breakthrough as a significant advance in understanding the functions and antithrombotic potential of (WE thrombin) in particular, and the approach of using engineered human proteins more broadly
The successful development of WE-thrombin would be a major medical breakthrough in antithrombotic therapy, ultimately saving thousands of lives worldwide each year, said the lead investigator Andrs Gruber, M.D., Ph.D., associate professor of medicine in the division of hematology and medical oncology, OHSU School of Medicine.
Thrombin is an enzyme that, paradoxically, has the capacity both to promote and prevent blood clotting. Balancing the two depends on a highly complex system of positive and negative feedback loops. Normal blood clotting is vital to minimize bleeding in the event of an injury. Excessive clotting can lead to thrombosis, the blockage of a blood vessel.
Heart attacks and strokes most often the result of blood clots remain two of the three leading causes of death and severe disability in the United States. The toll from these diseases persists at high levels in part because the drugs now relied on to stop or break up clots such as heparin or TPA, tis
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Oregon Health & Science University