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, professor in the department of biochemistry 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.
Fay, along with Dr Hironao Wakabayashi, a research assistant professor at the University of Rochester Medical Center and co-inventor, have filed a patent application for the factor VIII redesign used in the published study. Moving forward, Fay’s team will target additional calcium binding sites with the goal of making changes that further increase factor VIII potency.
“Our goal is to improve upon nature by developing gain-of-function factor VIII proteins that are superior to the factor VIII protein found in healthy individuals,” Fay said. “These more potent forms are not likely to occur naturally since they would theoretically result in excessive clotting, blocked arteries and heart attacks in otherwise healthy people. In patients with hemophilia, however, enhanced clotting is desirable.”