Proposal for generating new beta cells in a muted immune environment for type 1 diabetes

摘要

Background: Over the past decade, many immune tolerance agents have shown promise in the non-obese diabetic mouse model for prevention and reversal of type 1 diabetes but have not been successful in clinical trials among recently diagnosed type 1 patients. The trials from decades ago using Cyclosporine A in significantly lower dosages than used for organ transplantation and in similar dosages that have increased T regulatory cell populations in conditions such as atopic dermatitis, demonstrated very high initial insulin-free remission rates when administered immediately after diagnosis. Over time, all newly diagnosed type 1 patients given Cyclosporine A required insulin. Human trials with immune tolerance agents suggest that in addition to an immune tolerance agent, a beta cell regeneration agent may also be necessary to induce long-lasting remission among patients with recent onset type 1 diabetes. Methods: A randomized, double-blind prospective trial among recent onset type 1 diabetes patients has been designed using Cyclosporine A and a proton-pump inhibitor, which increases gastrin levels and has been shown to work through the Reg receptor to transform pancreatic duct cells into islets.