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Redesigned protein accelerates blood clotting

Researchers have doubled the potency of a protein that drives blood to clot, according to research to be published in the July 26 edition of Biochemistry. The study results may have profound implications for the treatment of hemophilia, the inherited blood disorder that causes easy or excessive bleeding in 30,000 Americans.

In most cases, hemophilia is caused by a lack of factor VIII, one of several proteins that enable blood to solidify, or clot, to plug wounds after injury. Current preventive treatment consists of genetically engineered factor VIII administered by injection, but one quarter of those born with no factor VIII suffer severe immune reactions that render the treatment inactive. In addition, current treatment costs as much as $200,000 per patient per year. Researchers at the University of Rochester Medical Center have been studying the structure of factor VIII for 20 years, and are making subtle changes in the protein with the goal of offering more effective, less burdensome treatment.

"We set out to design a version of factor VIII that would improve on the naturally-occurring form of the protein," said Philip Fay, Ph.D., professor in the Department of Biochemistry and Biophysics at the University of Rochester Medical Center, and the study's senior author. "A more potent form of factor VIII, one that could treat effectively with a lower dose, would reduce the cost and, potentially, avert immune reactions," Fay said.

Study Details

Blood clotting involves more than a dozen clotting factors, many named with roman numerals. They form a cascade of chemical reactions inside blood vessels following injury, with each factor, or complex of factors, activating the next in the chain. Factor VIII partners with factor IX to activate factor X, which creates a burst of thrombin, which in turn generates fibrin, the sticky protein strands that form a web-like clot over damaged tissue. Calcium, a metallic element,
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-3678
University of Rochester Medical Center
20-Jul-2005


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