A novel cofactor-based procoagulant protein as bypassing agent for hemophilia

Hemophilia is an X-linked bleeding disorder that results from a deficiency or defect in blood clotting factor VIII (hemophilia A) or factor IX (hemophilia B). Hemophilia patients are treated with protein infusions to replace the defective or missing protein. Unfortunately, up to 30% of patients develop an immune response to the infused protein, which renders the therapeutic protein inactive. Alternative treatment options for these patients consist of switching to infusions with other blood coagulation protein products. However, these therapies are expensive because of the limited effectiveness of these alternative proteins.

We will develop a new coagulation protein as an alternative therapy for these hemophilia patients. To do so, we make use of a novel strategy based on a naturally occurring variant of a coagulation factor V found in the venom of the Australian common brown snake Pseudonaja textilis. Strikingly, this snake venom factor V has several unique characteristics that make it much more effective in coagulation as compared to its human counterpart. Using this snake venom variant as a model and tool, we will engineer human factor V to make it more similar to the snake venom protein. The newly generated protein variants will be characterized using a wide array of in vitro and in vivo assays. The capacity of these protein variants to invoke an immune response will be established in collaboration with Dr. Federico Mingozzi, Associate Professor at the Université Pierre et Marie Curie, Paris. In doing so, we expect to develop a novel therapeutic protein that is more effective, more stable, and more safe, thereby improving the treatment options for hemophilia patients.