347-OR: ILV-001, a Myokine of Interest to Potentiate the Success of Pancreatic Islet Transplantation and Treat a Maximum Number of People with T1DM



Introduction and Objective: Islet transplantation is a promising therapeutic approach for people with unstable T1DM. The main challenge is to reduce the number of pancreases needed to treat a single person. In this context, we have recently demonstrated that ILV-001, a component of the muscle secretome, enables rapid uptake and lasting function of the graft. The aim of the project was to determine whether ILV-001 could reduce the quantity of pancreatic islets to be transplanted in order to normalize glycaemia in diabetic rats.Methods: Syngeneic rats rendered diabetic with streptozotocin were given or not (SHAM group) an intra-portal infusion of 5000 IEQ/kg untreated (control group) or pre-treated with 1µg/ml ILV-001. Transplanted animals either received or did not receive a daily intraperitoneal injection of ILV-001. Weight gain, glycemia, c-peptidemia, graft function and insulin requirements were assessed for 3 months.Results: Contrary to control group, transplantation of 5000IEQ/kg+ILV-001 improved glycemic control in diabetic rats and this from 3 days after islet injection. Moreover, whatever ILV-001 administration modality, c-peptidemia increased compared with the control group from 7 days post-injection. In addition, IPGTT tests showed an improvement in graft functionality with ILV-001 versus control group throughout the study. Finally, insulin requirements were significantly reduced in ILV-001-treated diabetic rats during metabolic follow-up.Conclusion: ILV-001 is a promising therapeutic agent to potentiate the effectiveness of islet transplantation. It reduces by at least half the number of islets needed to normalize glycemic control in people with T1DM.

Disclosure

A. Langlois: None. M. Pinget: None. C. Siobhan: None. K. Bouzakri: None.



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