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Gene Therapy Restores Blood Sugar Control to Near Normal


Several research teams in Asia, Europe, and North America are working on gene therapy strategies for promoting long-term insulin production in the liver to treat type 1 diabetes. One of the barriers to this form of therapy, however, is that once you've turned on production of insulin, you have to find a way to turn it off to avoid the problems associated with hypoglycemia, a condition caused by extremely low blood sugar levels, which can cause loss of consciousness, diabetic comas, and in extreme cases, death.

"Unlike other areas of gene therapy where you're missing some gene and it doesn't make a difference how much of the protein it makes, with insulin it's a double-edged sword: You not only have to make ... [enough] insulin ... you have to stop making the insulin when you don't need it," says Alvin Powers, MD, associate professor of medicine at Vanderbilt University and a physician in the Department of Veterans Affairs Medical Center in Nashville, Tenn., who reviewed the study for WebMD.

To do an end-run around the problem of maintaining proper glucose levels, the researchers added to their gene package a portion of a liver gene that is activated in response to changes in glucose levels.

"The new twist here is that they have engineered the cells so that not only do they make 'insulin,' but they also are regulated in their level of 'insulin,' and that the blood sugar and the 'insulin' level and the amount of 'insulin' that's put out or secreted by the liver cells is related," Powers says.

"But rodents are quite different from humans, with respect to maintaining glucose levels, and extending these results to human physiology may prove a challenge," writes Jerrold Olefsky, MD, from the University of California at San Diego, in an editorial accompanying the study. He notes that mice and rat livers produce glucose at much higher rates than human livers do, "so small effects of insulin on the liver may be able to control post-eating glucose levels in rodents, but may be less effective in humans."

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