Large numbers of islets are lost in the time immediately after a clinical islet transplant, through cell death or innate inflammatory injury. The authors previously demonstrated the positive impact of a series of inhibitors in mouse models on islet transplantation survival through reduction in early post-transplant cell death. Here they studied one specific inhibitor called IDN6556 in a large animal (pig) transplant model. Pigs receiving IDN6556 had lower fasting blood glucose level after transplantation and a higher percentage (100% vs. 33.3%) showed fasting blood glucose levels closer to normal. This translated into an enhanced metabolic reserve and acute insulin release for pigs in the treatment group. In conclusion, IDN6556 led to enhanced islet survival and function in this large animal islet transplant model.
Caspase Inhibitor IDN6556 Facilitates Marginal Mass Islet Engraftment in a Porcine Islet Autotransplant Model Transplantation 2012 Jul 15;94(1):30-5.
Investigators and Institutions:
The study was led by Dr. Shapiro and his colleagues at University of Alberta, Edmonton.
Ramifications for Individuals with Type 1 Diabetes:
Islet transplantation has been shown to have great efficacy in T1D individuals. One of the limiting factors is the shortage of islet cells such that many pancreases are needed to transplant one patient. This research is a promising approach to attain successful single-donor islet transplantation by improving islet survival and function.
This study was not supported by JDRF, but JDRF supported the prior rodent studies. JDRF is supporting a clinical trial in Edmonton testing this inhibitor in islet transplantation.