The immunomodulator Linomide: Role in treatment and prevention of autoimmune diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is considered to be an autoimmune disorder characterized by destruction of the pancreatic β-cells by auto-reacting lymphocytes. An attractive therapeutic approach to this disease would be to abrogate the autoimmune process at an early stage, thus preserving a critical mass of pancreatic β-cells necessary for maintenance of normal glucose tolerance. Linomide (quinoline-3-carboxamide, Roquinimex, LS 2616), is a novel, orally absorbed, immunomodulatory drug that has been shown to be effective in various models of autoimmunity without causing non-specific immunosuppression. In this review, we describe the efficacy of Linomide for ameliorating the autoimmune process and diabetes in the non-obese diabetic (NOD) model of IDDM when administered at early stages of the disease. We also show that advanced disease in the NOD mouse can be treated effectively by combining Linomide with therapeutic modalities designed to increase pancreatic β-cell mass. Subsequent clinical studies have shown that Linomide preserves β-cell function in individuals with new-onset IDDM. Based on these data, Linomide or derivatives thereof might be useful for treatment of human IDDM.