Grant: Doctoral: Vanier Canada Graduate Scholarships

Diabetes is a disease characterized by a relative insulin insufficiency and an associated hyperglycemia. It is one of the most prevalent diseases, affecting over 2.5 million Canadians and costing the Canadian health care system over $12 billion a year (CDA, 2009). Despite incredible advances in care, from the first insulin injection in 1922, to the first islet cell transplants by 1990, diabetes continues to be associated with an abundance of comorbidities, decreased quality of life, and a shortening of patients' lives. Importantly, all treatments available to date continuously fail to address perhaps the most fundamental problem all diabetics face - an eventual loss of functional insulin producing beta-cells in the pancreas. In genetic mouse models of diabetes, it has been demonstrated that the expression of embryonic transcription factors that are normally expressed during development and orchestrate the healthy development of the different tissues of the pancreas can induce expansion of beta-cells in adults. Investigating clinically relevant gene therapy technologies able to induce expression of these genes, could lead to a cure for diabetes. One such technology is the use of an adeno-associated virus (AAV). Researchers have recently characterized an incredible eighth serotype of the AAV family that is capable of efficiently delivering therapeutic genes selectively to cells of the pancreas. In support of both the safety and efficacy of these viruses, an AAV based drug (Glybera®) has been approved for clinical use in Europe. Using this technology, we intend to carefully express transcription factors in different cells of the pancreas, in an effort to induce their conversion to, and an associated expansion of insulin producing beta-cells. Such a treatment could be the basis for a cure that leads to diabetics avoiding thousands of insulin injections each year and saving the Canadian healthcare system billions of dollars.