International Pancreatic Islet Transplantation Association (IPITA), 2023 in San Diego, USA

October 26-29, 2023

Abstract :

ILV-001 a highly promising therapeutic agent for islet transplantation

A. Langlois ¹, A. Grabarz², M. Pinget^1,2, K. Bouzakri^1,2

1. DIATHEC, UMR 7294, Centre européen d’étude du Diabète, Université de Strasbourg, Boulevard Leriche, 67200 Strasbourg, France.

2. ILONOV, Boulevard Leriche, 67200 Strasbourg, France.

Introduction:

Our team has shown a bimodal effect on β-cells of muscle-secreted myokines from normal or insulin-resistant human skeletal muscle. We identified ILV-001, a component of the muscle secretome regulated by muscle fiber type and physical exercise, moreover naturally present in the extracellular matrix of the islet niche. Thus, we aimed at investigating the therapeutic potential of ILV-001 in protecting β-cell function and survival during islet transplantation.

Methods:

In vitro: Rat islets were incubated 24h ± ILV-001 (1µg/mL). Islet survival was assessed by TUNEL assay ± cytomix. Islet function was evaluated using GSIS test.

In vivo: 10000 IEQ/kg ± ILV-001 were injected intraportaly in diabetic syngeneic rats. For 3 months body weight gain, glycaemia, c-peptidemia and graft function (IPGTT) were followed. Inflammation was evaluated titrating plasmatic α₂-macroglobulin. Histology was performed on grafted islets.

Results:

In vitro: ILV-001 improves islet function and survival and potentiates insulin secretion after GSIS test.

In vivo: ILV-001 improves graft function in terms of glycaemia (p<0.001) and c-peptidaemia (p<0.01) and decreases exogenous insulin intake requirements. ILV-001 reduced inflammation 24h post graft with a lower plasmatic α₂-macroglobulin versus control with respectively 459±70 versus 903±191 µg/mL (p<0.05). Finally, histology showed a preservation of insulin positive cells with ILV-001 versus control at the end of study (69±3% versus 39±3% of β-cells/islet, p< 0.001).

Conclusion:

ILV-001 is a highly promising candidate for the achievement of a functional cure in T1D thanks to potent β-cell preservation and obtaining long term graft maintenance following islet transplant.