Scientists Hold Out Hope for Diabetes Cure

Partial success in mice highlights new treatment's potential, experts say

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By Ed Edelson
HealthDay Reporter

THURSDAY, March 23, 2006 (HealthDay News) -- Three years ago, scientists announced a new treatment had cured diabetes -- in mice.

But researchers reporting in the March 24 issue of Science say three separate attempts to replicate that pioneering study have proven only partially successful.

The results, while not stellar, still leave the cup of hope at least half-full for people with diabetes, experts say.

In fact, Dr. Denise L. Faustman, the scientist who performed the first study, contends the cup is still "100 percent full, because the new studies confirm that it is possible to stop the process by which the immune system mistakenly destroys insulin-producing islet cells." Islet cells reside in the pancreas, but are destroyed in the type 1 form of diabetes.

Faustman is director of Massachusetts General Hospitals Immunology Laboratory. Her group reported in 2003 that a two-phase treatment had restored islet cell function in mice with a condition similar to human type 1 diabetes, in which the body does not produce insulin.

Type 1 diabetes generally appears early in life and is much more difficult to treat than obesity-associated type 2 diabetes, in which the body's insulin production gradually declines.

Plans for a trial to see if type 1 diabetes can be reversed in humans are well underway at Massachusetts General Hospital, Faustman said, despite the partial failure of the three subsequent trials in mice.

In the original trial, the diabetic mice were first injected with TNF-alpha, a naturally occurring protein that stopped the immune system's attack on the islet cells. That was followed by an injection of spleen cells from healthy mice, used because they carry proteins that help immune cells to recognize and ignore normal tissue.

The idea was that the spleen cells would stop the autoimmune attack, giving transplanted islet cells time to restore insulin production. But, in a surprising development, no transplants were needed because insulin was produced by islet cells that suddenly grew on their own in the rodents' pancreas -- some of them transformed from the injected spleen cells.

Those same steps were taken in the three new studies, reported by researchers at Washington University School of Medicine, the University of Chicago and the Joslin Diabetes Center in Boston.

Again, diabetes was cured in some, but not all, of the mice -- four of 22 in the Washington University trial, seven of 22 in the University of Chicago trial, and more than half of those in the Boston trial.

What the researchers in all three trials did not see was the transformation of the injected spleen cells into insulin-producing cells, however.

"We were able to cure mice with established diabetes, [just] not as well as she did," said Anita S. Chong, an associate professor of surgery and a member of the University of Chicago research team. "But this second aspect of her work we were not able to replicate."

The big question now is why insulin production was resumed in just some of the mice, Chong said. There are two possibilities, she said -- either a small percentage of insulin-producing cells survived the initial autoimmune attack and swung back into action when the attack stopped, or new islet cells were being produced from surviving stem cells.

Either way, the result of the studies opens up a new route for diabetes therapy, Chong said, showing that "a diabetic mouse, even as an adult, has an ability to make new insulin-producing cells."

Dr. David M. Nathan, director of the Diabetes Center at Massachusetts General Hospital, said he's eager to see if the same thing can be done in humans. A proposal for human trial has been approved, Nathan said, and researchers are waiting on the development of a highly sensitive assay that can track immune cells that attack and destroy insulin-producing cells.

"Denise is working feverishly to perfect the assay," Nathan said. "It is trying to pick out a very small number of a huge population of cells, one in every 100,000. To try to go from mice to humans is a huge technical problem, and we cannot start any human studies until we have an assay for those autoimmune cells."

"We have patients who are coming in every day donating blood for testing," Faustman said. Her estimate is that it will take 18 months for the tests and equipment necessary for a human trial to be ready. The trial will use injections of a well-known molecule called BCG to try to reverse the immune system attack, she said.

Meanwhile, she said, "We are actually elated by these studies. For 20 years, the hope has been that humans can regenerate insulin-producing cells. When we began this work we were not even allowed to use the word 'regeneration' in our papers. By 2003, we were able to use the word. These three landmark papers are extraordinarily important."

More information

For much more on diabetes, head to the American Diabetes Association.

SOURCES: Denise L. Faustman, M.D., Ph.D., director, Massachusetts General Hospital Immunology Laboratory, Boston; Anita S. Chong, Ph.D, associate professor, surgery, University of Chicago; David M. Nathan, M.D., director, Diabetes Center, Massachusetts General Hospital, Boston; March 24, 2006, Science

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