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Bioengineered protein shows preliminary promise as new therapy for hemophilia
Date:10/23/2011

A genetically engineered clotting factor that controlled hemophilia in an animal study offers a novel potential treatment for human hemophilia and a broad range of other bleeding problems.

The researchers took the naturally occurring coagulation factor Xa (FXa), a protein active in blood clotting, and engineered it into a novel variant that safely controlled bleeding in mouse models of hemophilia. "Our designed variant alters the shape of FXa to make it safer and efficacious compared to the wild-type factor, but much longer-lasting in blood circulation," said study leader Rodney A. Camire, Ph.D., a hematology researcher at The Children's Hospital of Philadelphia.

"The shape of the variant FXa changes when it interacts with another clotting factor made available following an injury," added Camire. "This increases the functioning of the protein which helps stop bleeding." Camire is an associate professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

The study appears online today in Nature Biotechnology, and will be published in the journal's November 2011 print issue.

In hemophilia, an inherited single-gene mutation impairs a patient's ability to produce a blood-clotting protein, leading to spontaneous, sometimes life-threatening bleeding episodes. The two major forms of the disease, which occurs almost solely in males, are hemophilia A and hemophilia B, characterized by which specific clotting factor is deficient. Patients are treated with frequent infusions of clotting proteins, which are expensive and sometimes stimulate the body to produce antibodies that negate the benefits of treatment.

Roughly 20 to 30 percent of patients with hemophilia A and 5 percent of hemophilia B patients develop these inhibiting antibodies. For those patients, the conventional treatment, called "bypass therapy," is to use drugs such as factor VIIA and activated prothrombin complex concentrat
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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