Grant: Project Grant

Type 1 diabetes (T1D) occurs when islet cells in the pancreas lose the ability to regulate the amount of glucose (sugar) in the blood. Diabetes affects more than 10 million Canadians and costs our health care system more than $30 billion each year. The go-to treatment is ongoing injections of insulin, which sustain life but cannot fully substitute for the natural control of blood glucose by islet cells. It is now also possible to restore long-term glucose control in people with T1D through a one-time transplantation of islet cells from an organ donor. However, this option is currently suitable only for a small number of people with T1D, due in part to the need for lifelong anti-transplant-rejection drugs that suppress the immune system. In addition, the procedure often fails due to the death of the transplanted islet cells. Our proposal seeks to understand how islet cells survive and function after they are transplanted. For example, what are the elements that islets need to survive when they are transplanted outside the pancreas? What molecular pathways are involved in islet cell death following transplantation, and can they be blocked by new drugs to prolong transplant function? This work will leverage an effective new drug delivery method our team has developed that delivers anti-rejection drugs just to the transplanted islet cells rather than to the whole body, reducing the required dose and the side-effects of the drugs. In this proposal we will test our hypothesis that this mode of local drug delivery will enhance islet graft survival and function This study aims to overcome major clinical hurdles facing the wider uptake of islet transplantation. By reducing the risks associated with islet cell transplantation therapies we hope to extend the benefits of this treatment strategy to many more Canadians living with T1D.