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Research Update: Less is More with Synthetic Inhibitors for Activated Protein C

Millions of units of factor VIII (FVIII) and factor IX (FIX) are used annually to save the lives of people living with hemophilia.  Recently, a group of scientists from the University of Vermont and Cleveland State University discovered a technique that may significantly decrease the amount of FVIII and FIX needed to manage the symptoms of hemophilia by inhibiting the activity of a substance called activated protein C (APC). APC is a chemical naturally found in the blood that stops blood from clotting once a significant blood clot is formed.  It can down-regulate blood coagulation by inactivating factors in the blood that play a role in forming clots. 

Previous studies have shown that organisms that cannot generate APC exhibit clotting problems.  This observation prompted Dr. Butenas and his colleagues in the study to investigate whether inhibiting APCs can enhance clotting in subjects with hemophilia.  Through a series of laboratory experiments, the researchers developed specific APC inhibitors capable of preventing it from down-regulating blood coagulation.  Based on these lab results, the team ran computer simulations to learn how these inhibitors, at specific doses, could decrease the amount of FVIII required to clot blood.  By using specific quantities of certain APC inhibitors, the scientists found that they were able to “partially compensate for severe hemophilia.” The research team advocates for scientists to continue researching APC inhibitors and how they may improve factor replacement therapy for people with severe hemophilia.

Source: Butenas, S, et al. Peptidomimetic Inhibitors for Activated Protein C: Implications for Hemophilia Management. Journal of Thrombosis and Haemostasis. 2006; 4: 2411-2416.


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