Targeted IL-22 Improves Glucose Tolerance and Reduces Hepatic Steatosis and Hepatic Fibrosis in Murine Models of Diabetes and Liver Disease

Abstract

The cytokine interleukin-22 (IL-22) is an inhibitor of cellular stress. In HFD murine models, systemic IL-22 is efficacious to restore glucose tolerance, reduce circulating triglycerides and hepatic steatosis, and improve AST:ALT ratio, but is also associated with gut and skin toxicity. As an approach to maintain efficacy without skin/gut adverse effects we have developed a prototype IL-22-based bispecific biologic drug candidate (IL-22-ScFv) which is targeted towards the pancreas and liver. In mouse models of T2D and NAFLD/NASH twice-weekly subcutaneous administration of IL-22-ScFv provides numerous therapeutic and metabolic benefits. After IL-22-ScFv administration for four weeks in HFD mi..