Experimental Therapy Reverses Type 1 Diabetes in Mice

MONDAY July 30, 2007 -- Researchers have accomplished what might be a cure of type 1 diabetes -- at least in mice --- and they're taking the first steps toward a human trial.

Type 1 diabetes is the autoimmune form of the disease, affecting about five percent of diabetics. It usually emerges in childhood and occurs when the body's immune system attacks insulin-producing beta cells in the pancreas.

Now, a three-drug regimen that not only stops the destruction of beta cells but also preserves the function of cells that receive and metabolize insulin has eliminated type 1 diabetes in laboratory mice, said lead researcher Maria Koulmanda, director of nonhuman primate research at the Transplant Research Center, Beth Israel Deaconess Medical Center in Boston.

Her team published its report July 30 in this week's online edition of the Proceedings of the National Academy of Sciences.

"We stopped the progression of automimmunity. The animals could become normoglycemic," meaning they had normal levels of blood sugar, Koulmanda said.

Another major discovery is that inflammation appears to play a major role in type 1 diabetes, she added. In fact, one drug used in the treatment regimen reduced the inflammation of cells that metabolize insulin.

"Basically, by blocking inflammation, we were getting the animals to be insulin-sensitive," Koulmanda said.

Another drug successfully reduced the autoimmune destruction of beta cells, but that was not the key to reversing the disease, she said. Instead, success was linked to blocking inflammatory processes that impair cells' responses to insulin.

Some of the cells involved in insulin metabolism were found to be resistant to insulin's effects -- a common phenomenon seen in much more common, adult-onset, obesity-linked type 2 diabetes, Koulmanda said. "This is the first time anyone has seen insulin-resistant cells in type 1 diabetes," she noted.

A course of treatment lasting less than four weeks restored normal blood sugar function in the test mice. In contrast, mice that did not get the treatment died during that month-long period.

Based on these promising results, the first work need to start a human trial of the regimen are about to begin, said Dr. Terry B. Strom, director of the Transplant Research Center.

"We have tried something like this for monkey models," he said. "The results have been very good."

The next step will be tests to ensure that the regimen is safe for human use.

"We anticipate toxicology trials very soon," Strom said. "We are making the proteins needed for those trials."

The fact that success was achieved in the mice trials with a relatively short course of treatment indicates that, for humans, "one might be able to use relatively brief periods of treatment to restore normal function," he said.

More information

There's more on type 1 diabetes at the U.S. National Library of Medicine.

Posted: July 2007


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