An antibody that can functionally replace the missing protein in a type of hemophilia reverses the inability to stop bleeding in a non-human primate model of the disease, as reported in a paper published online this week in Nature Medicine.
Patients with hemophilia A lack the coagulation protein factor VIII and are typically treated by injection of FVIII protein. However, there is a need for new treatments, as over time patients often develop antibodies to the injected FVIII that block its efficacy. Even when effective, FVIII must be given frequently by intravenous injection, which poses a problem, particularly for children.
In a new treatment strategy, Takehisa Kitazawa and colleagues generated an antibody with factor VIII activity. Factor VIII works by bringing two other proteins in the blood coagulation cascade, factor IXa and factor X, into contact with each other. The new antibody mimics factor VIII, binding to and positioning factor IXa and X. This antibody restored coagulation activity in blood from humans with hemophilia, even those with factor VIII antibodies, and reduced bleeding in a preclinical model of hemophilia A in cynomolgus monkeys.
Compared to factor VIII injection, this antibody has the potential advantages of being unaffected by factor VIII antibodies and being easier to use (the antibody could be injected under the skin and would not require frequent injections). Further optimization of the antibody may be needed before it is ready to be tested in clinical trials.