Type 1 Diabetes Immunotherapy - Successes, Failures and Promises

Abstract

Type 1 diabetes is an autoimmune disease that usually strikes during adolescence resulting in uncontrolled blood glucose levels. Auto-reactive T-cells target the insulin producing beta cells of the pancreas resulting in their destruction. The only treatment currently available is lifelong administration of insulin to bring blood glucose levels back under control. The identification of insulin and its mass production were the first major success in the treatment of the disease. Building on the work of others, Frederick Banting and Charles Best demonstrated the ability of insulin to maintain normoglycemia in pancreatectomized dogs in 1921 (Banting; Best; Collip, et al., 1922) and with the help of Eli Lilly the mass production of insulin was under way by 1922 for clinical use. Prior to this the disease was fatal by 3 years. No less than 4 Nobel prizes have been rewarded over the years for research on insulin’s indentification, sequence, structure, and the production of recombinant human insulin. Despite the success of insulin therapy, it is now obvious that even rigorous control of blood glucose with insulin injections only delays, but does not prevent the development of diabetic complications (The DCCT Research Group, 1993). Diabetic complications, which include cardiovascular disease, diabetic retinopathy, kidney failure, and neuropathy, account for significant diabetes-related patient morbidity and mortality. Islet transplantation has been attempted to restore the normal release patterns of insulin, but sufficient source donors are limiting, the possibility of lifelong anti-rejection drugs may prove worse than diabetes, and the autoimmune process that destroyed the original beta cells are still active (Huurman; Hilbrands; Pinkse, et al., 2008, Marzorati; PileggiR Huurman; Hilbrands, et al., 2009, Van Belle&von Herrath, 2008). Therefore therapeutics that modify the immune response and restore normal immune function are necessary to improve the outcomes of patients with type 1 diabetes. Little has changed in the primary treatment of type 1 diabetes over the last 90 years, but immunotherapy techniques hold the promise of finding a true cure.