Discovery provides key for development of improved blood-clotting drugs for hemophiliacs and better blood-thinning medications for those at risk of stroke and heart attack

SEATTLE - For the first time, researchers have described the structure of a key blood-clotting protein implicated in hemophilia A, the most prevalent and serious type of hemophilia, an inherited disorder that causes recurrent, uncontrolled bleeding, most often into the joints.

Knowing the structure of this protein, called factor VIII, gives scientists a first-hand glimpse at the subtle changes - often involving just a single errant atom - that cause this devastating bleeding disorder, which affects about one in 10,000 American males. This discovery also provides a key to the development of new drugs - better clotting agents for hemophiliacs and improved anticoagulants for those at risk of stroke and heart attack.

The discovery, a collaborative effort between researchers at the Fred Hutchinson Cancer Research Center and the University of Washington, will be reported tomorrow (Thursday, Nov. 25) in the British journal Nature. The Hutchinson Center team was led by senior author Barry L. Stoddard, Ph.D., and included Kate Pratt, Ph.D., and Betty Shen, Ph.D., all of the Center's Basic Sciences Division. The UW group was led by Earl W. Davie, Ph.D., and Kazuo Fujikawa, Ph.D., both of the Biochemistry Department within the School of Medicine.

"Solving the structure of this protein tells us a great deal about how it works. It also explains very specifically, at the atomic level, why factor VIII doesn't work in many people with hemophilia A," says Stoddard, a member of the Hutchinson Center's Basic Sciences Division and an affiliate associate professor of biochemistry at UW.

Using a technique called X-ray crystallography - an ultra-high-powered form of microscopy that reveals the structure of matter at the atomic level - the researchers uncovered the architecture of a
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Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
23-Nov-1999