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JDRF invites letters of intent (LOI) from single investigators or groups of investigators to develop and conduct studies aimed at the discovery and validation of novel pathways and targets to promote the regeneration of functional human beta cell mass. Both T1D (type 1 diabetes) and T2D (type 2 diabetes) are characterized by declining function and loss of insulin-producing beta cells of the pancreatic islet; all T1D and the majority of T2D patients ultimately depend on insulin therapy due to the loss of adequate functional beta cell mass. Disease modifying regenerating therapies to restore functional beta cells mass are needed for both forms of diabetes.
Beta cell regenerating therapies will be needed to induce an increase in functional beta cell mass in order to achieve a cure for both major forms of diabetes. Recent major scientific developments provide a range of potential strategies for the discovery of beta cell regenerating therapies. At the same time, it is desirable to discover other novel pathways and targets to safely and specifically promote functional human beta cell replication.
In addition, some evidence suggests that beta cell regeneration may be achieved by promoting neogenesis of mature beta cells from a pancreatic progenitor cell. However, more work needs to be done to characterize these putative progenitor cells, and establish that this could represent a viable strategy to induce regeneration of mature, functional human beta cells. Alternatively, transdifferentiation of other cell types in the islet, such as alpha cells, to become functional beta cells has been described – at least in animal models. Better understanding of the pathways involved in these processes may enable discovery of regenerating therapies to increase functional beta cell mass and function in diabetes. The ability to establish the relevance of these pathways to the human islet/beta cell is crucially needed.
Recent data suggest that human beta cells exhibit cellular plasticity as a result of pathophysiological conditions. De-differentiation can be found after immune and metabolic stress resulting in a cell type with greatly reduced insulin secretory capabilities and some level of immune protection. Further understanding of the pathways controlling these processes could lead to therapies to “reawaken” or restore sub-functional beta cell mass. Such therapies could be disease modifying in the diabetic state and result in reversion to normoglycemia.