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 beta-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 beta-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 beta-cell mass. Subsequent clinical studies have shown that Linomide preserves beta-cell function in individuals with new-onset IDDM. Based on these data, Linomide or derivatives thereof might be useful for treatment of human IDDM.
Gross
D J
DJ
Department of Endocrinology and Metabolism, Hadassah University Hospital, P.O. Box 12000, 91120, Jerusalem, Israel. gross@vms.huji.ac.il
Weiss
L
L
Reibstein
I
I
Hedlund
G
G
Dahlén
E
E
Rapoport
M J
MJ
Slavin
S
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex