GAD65 Autoantigen Treatment Ineffective in Type 1 Diabetes

Treatment with GAD65 antigens failed to prevent progression of type 1 diabetes, according to a recently published study. The finding is a setback to our attempts to curb the disease by manipulating the immune system.

Insulin is produced by the beta cells of the pancreas. In type 1 diabetes, antibodies are produced against these cells. The antibodies destroy the cells, thus leading to a lack of insulin and diabetes. The phenomenon is an example of autoimmunity, where the body’s immune system fights its own cells. People with the condition have to take insulin throughout their life. Though type 1 diabetes can occur at any age, it is most often diagnosed in children, adolescents and young adults. A number of studies are being conducted to find new and more convenient treatments for type 1 diabetes.

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Glutamic acid decarboxylase (GAD) is an enzyme responsible for the production of a nerve chemical called GABA. It is present in the brain as well as the beta cells of the pancreas. It exists in two forms, GAD67 and GAD65.

Antibodies against GAD have been observed in type 1 diabetes patients. Thus, it has been suggested that the antibodies react against GAD in type 1 diabetes. This is thought to be one of the mechanisms that lead to destruction of the pancreatic beta cells.

Based on this assumption, researchers are trying out treatment with GAD autoantigens with the hope that they may interfere with the autoimmune process and prevent further damage to the pancreas.

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A study from the New England Journal of Medicine evaluated whether alum-formulated GAD65 (GAD-alum) could prevent further damage to the pancreatic beta cells and permit preservation of some pancreatic function in patients with newly diagnosed type 1 diabetes. GAD-alum is a recombinant human GAD in a standard vaccine formulation with alum. The study was conducted on 334 patients between the ages of 10 and 20 years within three months of diagnosis of type 1 diabetes. The patients received either four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo.

The study found that insulin secretion declined at a similar rate in all the individuals included in the study at the end of 15 months irrespective of whether they received GAD-alum or not. Parameters like glycated hemoglobin levels and mean daily dose of insulin were also not altered by the treatment. The adverse effects were not significantly different in the two groups.

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The results of this study were in contrast to a previous smaller study that showed a benefit of GAD autoantigens in type 1 diabetes. Further studies will be required to establish the use of these autoantigens in the treatment of type 1 diabetes mellitus.

Reference:

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1. GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus; Johnny Ludvigsson et al; N Engl J Med 2012; 366:433-442.

Source-Medindia