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Regenerative Therapies for Diabetes - Previous and current research

The pathogenesis of diabetes mellitus hinges on the loss of pancreatic islet beta cells which in type 1 diabetes is mediated by autoimmunity. We have studied how autoimmunity develops in the course of the disease in children, the target beta cell antigens and epitopes, and the factors that predispose to autoimmunity. We discovered that autoimmunity develops most frequently around 1 to 2 years of age and that the proinsulin prohormone is the primary target antigen. We have also demonstrated that maternal diabetes protects against the development of beta cell autoimmunity. The findings have led to the first primary vaccine study that we are conducting as a multi-center international trial.

This Pre-POINT trial identified doing of oral insulin that could engage the immune system and which now forms the basis for further primary and secondary prevention trials. These include Pre-POINT Early, which will test oral insulin versus placebo treatment at age 6 months. Our overall goal is to prevent the autoimmune mediated destruction of islet beta cells. Therefore we are also interested in the development of markers that identify persons with high risk for developing type 1 diabetes.

These include genetic markers, autoantibodies against islet beta cells, and T cells responses to beta cell antigens. Since the autoreactive immune cells are rare, we develop high end methods and analyses on single cell gene and protein expression that we use to identify response to therapy in our clinical trials, and to understand the transition from na├»ve to memory autoreactive responses in genetically susceptible children.  Website of type 1 diabetes prevention study "Pre-POINT".

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