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Gene therapy prevents onset of hyperglycemia in diabetes prone mice
Jun 3, 2006 - 9:50:00 AM, Reviewed by: Dr. Sanjukta Acharya
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"We've shown it is now possible to efficiently insert genes into beta cells in a living organism, allowing us to analyze the effects that different gene products have on the progression of type 1 diabetes"
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By University of Pittsburgh Medical Center,
Using state-of-the-art gene therapy techniques, University of Pittsburgh investigators have successfully prevented the onset of elevated blood sugar, or hyperglycemia, in diabetes-prone mice by inserting a gene encoding for a cytokine -- a protein that stimulates or inhibits the proliferation or function of immune cells -- into their insulin-producing cells. According to the investigators, these findings, which are being presented at the American Society of Gene Therapy Annual Meeting in Baltimore, May 31 to June 4, have significant implications for the prevention of type 1 diabetes.
More than 700,000 Americans have type 1 diabetes, an autoimmune disorder in which the body errantly attacks the cells of the insulin-producing cells of the pancreas, causing chronic hyperglycemia and complications such as blindness, kidney failure, heart disease and nerve damage. Previously known as juvenile diabetes, type 1 diabetes is usually diagnosed at a very early age but is sometimes not diagnosed until the individual reaches adulthood.
In this study, the Pitt researchers used a gene-delivery vehicle known as an adeno-associated virus to insert genes for either of two cytokines, interleukin-4 (IL-4) or interleukin-10 (IL-10), into the insulin-producing beta cells of non-obese diabetic (NOD) mice. Following gene delivery, expression of IL-4 in beta cells prevented the onset of hyperglycemia in NOD mice, whereas beta cell expression of IL-10 accelerated the onset of hyperglycemia.
According to lead author Khaleel Rehman Khaja, Ph.D., senior research associate, department of molecular genetics and biochemistry, University of Pittsburgh School of Medicine, results from this animal study suggest that gene therapy is a viable method for preventing the onset of type 1 diabetes in genetically at-risk people.
"We know that the prevention of type 1 diabetes requires early intervention in the autoimmune process directed against beta cells of the pancreatic islets. Although the exact mechanism is still under investigation, we believe the protection we observed in our study is due to IL-4 stimulating an increase in regulatory T cells, which are known to suppress the activation of the immune system. However, the most important aspect of our study is that we've shown it is now possible to efficiently insert genes into beta cells in a living organism, allowing us to analyze the effects that different gene products have on the progression of type 1 diabetes," he explained. 
- American Society of Gene Therapy Annual Meeting in Baltimore, May 31 to June 4
www.upmc.edu
Others involved in this study include Zhong Wang, Ph.D., Xiao Xiao, Ph.D., and Paul D. Robbins, Ph.D., departments of molecular genetics and biochemistry and orthopaedic surgery, University of Pittsburgh School of Medicine.
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