Researchers demonstrated improved clotting in hemophilia A and B mice expressing human activated protein C (APC) after the administration of human APC mAb 1573 (HAPC1573), as published in Blood Advances.
HAPC1573 is a monoclonal antibody that selectively blocks human protein C anticoagulant activity. The study was undertaken in an effort to overcome the limitations of factor replacement and find alternative approaches to achieving hemostasis in patients with hemophilia.
“Current factor replacement therapies have major limitations such as the short half-life of the factors and development of inhibitors,” the authors explained. “Alternative approaches to rebalance the hemostasis by inhibiting the anticoagulant pathways have recently gained considerable interest.”
“In this study, we tested the therapeutic potential of a monoclonal antibody, HAPC1573, that selectively blocks the anticoagulant activity of human activated protein C.”
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The research team established the mouse model by genetically replacing the murine Proc gene with the human PROC, thereby creating PROC+/+;F8-/- or PROC+/+;F9-/- mice. The mice, which had similar bleeding rates to F8-/- or F9-/- mice, were pretreated with HAPC1573.
They found that the PROC+/+;F8-/- mice had shortened tail bleeding times and improved thrombin generation, and that both PROC+/+;F8-/- and PROC+/+;F9-/- mice had significantly reduced joint swelling and mortality in a similar manner as mice treated with factor VIII or factor IX. These results confirm the modulatory effect of HAPC1573 on APC, enhancing coagulation.
Furthermore, the team demonstrated that HAPC1573 improved the clotting time in factor V-, VII-, VIII-, IX-, X-, XI-, and von Willebrand factor-deficient human plasma. They concluded that selectively blocking the anticoagulant activity of human APC with monoclonal antibody treatment could represent an alternative therapeutic or prophylactic approach to improve clotting time in patients with hemophilia.
Jiang M, Yang F, Jiang Y, et al. Blocking human protein C anticoagulant activity improves clotting defects of hemophilia mice expressing human protein C. Blood Adv. Published online April 7, 2022. doi:10.1182/bloodadvances.2021006214