Grant: Master's Award: Canada Graduate Scholarships

Hemophilia A is an inherited bleeding disorder caused by low levels of factor FVIII (FVIII), an essential protein in the blood clotting process. This condition usually affects males and is characterized by prolonged bleeding from injuries and, in severe cases, spontaneous bleeding into the joints and muscles. To treat these symptoms, hemophilia A patients are given FVIII intravenously. Persons with hemophilia A do not produce their own FVIII and so in some cases the administered FVIII is recognized by the immune system as a foreign protein. As a result, 30% of severe hemophilia A patients receiving FVIII develop antibodies against the protein. These antibodies, known as inhibitors, prevent the protein from working properly, making treatment with FVIII ineffective. In such cases, the patient’s anti-FVIII antibodies must be eliminated in order to continue treatment for bleeding symptoms. The only method currently used to achieve this is immune tolerance induction (ITI), a therapy which requires frequent injections of high doses of FVIII over long periods of time. Since ITI is expensive and difficult to administer, it is important to develop drugs that could increase the efficiency of this therapy. ITI is thought to work by killing memory B cells, a type of cell required for the production of antibodies against FVIII. We therefore plan to investigate if a modified version of the FVIII protein, FVIII-Fc, is able to eradicate memory B cells more efficiently than FVIII and improve ITI performance. This could increase the quality of life of hemophilia A patients with inhibitors and decrease costs to the health care system.