Development of Therapeutic Strategies to Regenerate Pancreatic Beta Cells: Towards a Disease-Modifying Treatment for Type 1 Diabetes.

During type 1 diabetes (T1D) pancreatic beta cells are targeted by the immune system leading to apoptosis, insulin deficiency and hyperglycaemia. T1D is associated with many co-morbidities and increased risk of all-cause mortality. Insulin injections are a lifesaving treatment, yet are limited by the difficulty matching supply with demand, weight gain and hypoglycaemia. Islet and stem-cell transplantation are limited by the need to prevent immune rejection of the allograft, ectopic insulin release and questions over long term function. Moreover, it is unlikely that islet and stem cell transplants will become available for all those living with T1D. New disease-modifying approaches are urgently needed to restore endogenous beta cell function and stable glycaemic control in T1D. In this cross-disciplinary project we will identify, develop and validate new therapeutic strategies for promoting beta cell regeneration in the pancreas, to prime onward drug development programmes with clear line of site toward clinical trials. We will focus on screening for drug candidates that stimulate formation of new beta cells in the pancreas using an innovative phenotypic screening assay coupled with robust target deconvolution. A complementary aim will evaluate the therapeutic utility of stimulating beta cell proliferation (expansion) using a drug candidate and genetic models.