Grant: Operating Grant: Industry-partnered Collaborative Research - Rx&D partner

Hemophilia A is the most common severe inherited bleeding disorder in humans. The severe form of the disease results in spontaneous bleeding into joints and muscles, resulting in long-term chronic pain and disability. The current treatment for hemophilia A involves the intravenous infusion of factor VIII protein concentrates, derived from either donated plasma or from recombinant DNA approaches. This treatment is safe and effective but there are limitations to the therapy: the requirement for intravenous infusion is inconvenient and challenging in young children; approximately 25 per cent of patients develop antibodies to the infused factor VIII, and global access to the concentrates is limited by supply and cost. In this research project, we aim to continue our studies of novel therapeutic approaches to hemophilia A using a well established dog model of the disease. Hemophilia A occurs spontaneously in dogs and the colony of mixed breed miniature schnauzer/beagles has been maintained at Queen's University for the past 30 years. These dogs have severe hemophilia and show a similar pattern of spontaneous bleeding to their human counterparts. The research proposal has four aims. First, we aim to continue with the long-term maintenance and investigation of the hemophilic dog colony at Queen's. This objective requires the support and coordination of a complex infrastructure involving specialized animal housing, a team of experienced veterinary technologists and veterinarians and the provision of an array of laboratory tests to evaluate blood clotting in the dogs. The next two aims, involve extensions of our previous assessment of gene and cell-based treatments for hemophilia. The rationale for both of these objectives is supported by recent successes in the mouse model of hemophilia. Finally, we will continue to collaborate with industrial partners to determine the safety and efficacy of novel hemophilia treatments in standardized pre-clinical testing protocols.