Scientists have tweaked the structure of a protein so that it gets blood to clot 50 times faster than it normally does. The advance, described in the current issue of the Proceedings of the National Academy of Sciences, could lead to more powerful and cheaper treatments for hemophilia.
Hemophiliacs lack one of several proteins, known as clotting factors, that work together to stanch blood loss. Injections of the missing factors are expensive and are sometimes rejected by the immune system. But one of the clotting proteins--factor VII--could serve as an excellent replacement on two counts: It occurs naturally in nearly every hemophiliac and thus is not rejected as foreign; and it can, under the right conditions, stand in for the more commonly missing factors.
Hoping to improve the action of factor VII, biochemist Gary Nelsestuen of the University of Minnesota, St. Paul, and his colleagues tried to alter its ability to bind to membranes, a critical step in starting a clot. When the scientists strategically replaced two amino acids, the new protein glommed onto membranes more readily and steadfastly than natural factor VII does. In the test tube, the altered version sped blood clotting activity by as much as 50 times.
The heightened bonding to membranes is fascinating, says Barbara Furie, a biochemist at Beth Israel Deaconess Medical Center in Boston. But she says it's too early to predict how the altered protein will behave in people.