Clinical Update on the Use of Immuno Modulators (antiCD3, GAD, Diapep277, Anti-IL1) in Type 1 Diabetes

Paolo      Pozzilli; Chiara      Guglielmi; Daria      Maggi; Angela      Carlone; Raffaella      Buzzetti; Silvia      Manfrini

doi:10.2174/138161211798157531

Abstract

In type 1 diabetes, beta cells are attacked and destroyed by auto reactive T cells causing major impairment of blood glucose metabolism and, ultimately, the development of life-threatening complications. Currently, the treatment of this chronic disease is based on the use of endogenous insulin and no curative therapies are available. Treatment approaches in this respect need to be directed toward the primary causes of the disease tackling beta cells auto reactive T cells.

The goal of any curative intervention in type 1 diabetes is the preservation of insulin-secreting cells. This may be achieved by the abrogation of the pathogenic reactivity to beta cell auto antigens while preserving full capacity to generate a normal immune response against foreign antigens.

In this review, some of the most promising drugs for immune intervention in type 1 diabetes are presented and discussed including phase 3 clinical trials that involve: DiaPep277, Anti-CD3 Otelixizumab, Glutamic Acid Decarboxylase (GAD) and anti-IL1 receptor antagonist. These approaches are currently being tested in international multicenter trials and all of them have a very similar outcome in terms of a beneficial effect on beta cells.

Keywords: Type 1 diabetes, Autoimmunity, Immuno intervention, Immuno tolerance, GAD, Diapep 277, Anti-CD3, Anti-IL1 receptor antagonist, endogenous insulin, pro-inflammatory cytokine