(aPCCs) to restore blood clotting capability. But these agents are costly (as much as $30,000 per treatment) and not always effective.
In the current animal study, Camire said researchers were able to show the variant protein is more effective at a lower dose than FVIIa.
Goal: creating new treatment options
The range of options for hemophilia patients could improve if the study results in animals are duplicated in humans.
“The variant we have developed puts FXa back on the table as a possible therapeutic agent,” Camire said. Naturally occurring (wild-type) FXa, due to its particular shape, is not useful as a therapy because normal biological processes shut down its functioning very quickly.
By custom-designing a different shape for the FXa protein, Camire’s study team gives it a longer period of activity, while also limiting its ability to engage in unwanted biochemical reactions, such as triggering excessive clotting.
“This potentially could lead to a new class of bypass therapy for hemophilia, but acting further downstream in the clot-forming pathway than existing treatments,” said Camire, who has investigated the biochemistry of blood-clotting proteins for more than a decade.
When the FXa variant was infused into mice with hemophilia, it reduced blood loss after injury, and safely restored the animal’s blood clotting ability. Further studies are necessary in large animal models to determine whether this approach can become a clinical treatment for hemophilia patients who have developed inhibitors, or even more broadly as a drug for uncontrolled bleeding in other clinical situations.
About the study
Funding support for this research came from the National Institutes of Health, Pfizer Inc., and the National Hemophilia Foundation. The first author of the study was Lacramioara Ivanciu, PhD, of The Children’s Hospital of Philadelphia. Other co-authors with Camire were from CHOP, Pfizer, and the Perelman School of Medicine of the University of Pennsylvania.
Ivanciu L, Toso R, Margaritis P, Pavani G, Kim H, Schlachterman A, Liu JH, Clerin V, Pittman DD, Rose-Miranda R, Shields KM, Erbe DV, Tobin JF, and Arruda VR, Camire RM. A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia. Nature Biotechnology. 2011 Oct 23; 29(11):1028-33. doi: 10.1038/nbt.1995. Read the abstract.