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Gene therapy cures Type 1 diabetes in rodents


November 24, 2000: Type 1 diabetes, previously known as juvenile diabetes, is caused by the destruction of insulin-producing beta cells in the pancreas. This destruction occurs when the immune system mistakenly attacks the beta cells. The absence of insulin means that people with diabetes have high blood glucose and associated complications: kidney, eye and nerve conditions as well as heart and vascular disease. New findings by Korean and Canadian research teams lay the groundwork for clinical trials on the use of gene therapy to cure autoimmune Type 1 diabetes in people.

The researchers used a recombinant adeno-associated virus which functions as a vehicle to transport a single-chain insuline analogue (SIA) into the liver of diabetic rodents. The SIA gene contains a glucose regulator.When the glucose level in the blood rises, the gene is activated. It then releases a modified version of insulin that perfectly controls blood glucose. When treated with this genetic therapy, the animals no longer suffer the symptoms of Type 1 diabetes. Their blood glucose levels are normal within 1– 2 weeks of treatment and remain normal with no apparent side effects.

Until now, the insertion of an insulin-producing gene into the body has been plagued with problems: the failure of the inserted gene to function reliably over time, the failure of the gene to regulate blood glucose levels, and the failure of the gene product to be effectively metabolized into insulin.

Lee et al.'s technique utilizes a glucose-responsive promoter which regulates blood glucose levels. This is certainly a step in the right direction, but in their trials, there was a delayed and prolonged response of insulin secretion following glucose injestion. While this did not result in significant hypoglycemia in the rodents, it is indicative of the complications that could arise in applying this therapy to humans.



Reference

Lee, C.L., S.-J. Kim, D.-S. Kim, H.-C. Shin and J.-W Yoon. 2000. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 408:483325.

Links

"Find-a-Cure.com" is a comprehensive page with numerous links. Major components of this page include news, research, Islet cell focus, diabetes biology, genetics, and references. Another interesting facet of this page is its 3-D insulin viewer.
http://www.find-a-cure.com

Sansum Medical Research Institute has extensive information on various components of diabetes research including pathology, clinical trials, and immunology
http://www.sansum.org



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