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Gene Therapy Restores Blood Sugar Control to Near Normal

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"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."

In addition, both standard insulin injections and experimental gene therapies are capable of controlling glucose fluctuations that occur over a span of hours, but glucose levels in the body are normally regulated minute by minute, Powers points out. "It's much easier to cure diabetes in rodents than it is in people," he tells WebMD, "and the field is littered with things that have worked in rodents but wind up not working in humans. This study is more in the proof of principle area."

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