Therapy with GAD in diabetes

Diabetes/Metabolism Research and Reviews - Tập 25 Số 4 - Trang 307-315 - 2009
Johnny Ludvigsson1,2
1Division of Pediatrics and Diabetes Research Centre, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
2For the Linköping Diabetes Immune Intervention Study Group (Johnny Ludvigsson MD, PhD, Rosaura Casas PhD, Maria Faresjö PhD, the PhD students Stina Axelsson, Mikael Chéramy, Maria Hjorth, and Mikael Pihl).

Tóm tắt

AbstractThe enzyme glutamic acid decarboxylase (GAD) is of great importance for the neurotransmission in the central nervous system, and therefore of interest for treatment of pain and neurological disease. However, it is also released in pancreas although its role is not quite clear. GAD is a major auto‐antigen in the process leading to type 1 diabetes with both a clear cell‐mediated immune response to GAD and auto‐antibodies to GAD (GADA), which can be used as a predictor of diabetes. Administration of the isoform GAD65 can prevent autoimmune destruction of pancreatic beta cells in non‐obese diabetic (NOD) mice and the subsequent need for exogenous insulin replacement. In Phase I and II studies an alum‐formulated vaccine (Diamyd) has shown to be safe, and in a dose‐finding study in Latent Autoimmune Diabetes in Adults (LADA) patients 20‐µg was given subcutaneously one month apart indicating preservation of residual insulin secretion. A double‐blind randomized Phase II trial in 70 patients (10–18 years old) with recent‐onset type 1 diabetes showed significant preservation of residual insulin secretion and a GAD‐specific immune response, both humoral and cell‐mediated, but no treatment‐related adverse events. With this promising background further studies are on their way, both intervention in newly diagnosed type 1 diabetic patients, and trials to prevent the disease. Copyright © 2009 John Wiley & Sons, Ltd.

Từ khóa


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Diabetes/Metabolism Research and Reviews

Tập 25 Số 4

307-315

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