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Researchers Cure Diabetes in Mice

Technique holds promise for humans, but much more money needed

THURSDAY, Nov. 13, 2003 (HealthDayNews) -- Massachusetts researchers say they have cured type 1 diabetes in mice.

And the technique they used -- injecting spleen cells that remarkably turned themselves into insulin-producing cells -- holds great promise for people with the disease. However, the scientists say, a lack of funding for the necessary human clinical trials is hampering their work.

The researchers, led by Dr. Denise L. Faustman, director of Massachusetts General Hospital's Immunobiology Laboratory, are reporting in the Nov. 14 issue of Science that their technique seems applicable to other autoimmune conditions, in which the body's immune system attacks its own tissue.

"We must get 500 calls a month from people who want to be in clinical trials," Faustman says. "The enthusiasm of the patient population is impressive."

"There is a huge amount of momentum required that people don't appreciate in moving from raising $1 million dollars a year to raising $20 million a year to get human trials started," she adds.

The animal studies have been financed primarily by the Iacocca Foundation, set up by automotive legend Lee Iacocca to support diabetes research after his wife, Mary, died of complications of the disease. But "they don't have the resources to scale up to human clinical trials," Faustman says.

The demand for human trials of the technique is there, Faustman says, expressed by patients who must give themselves insulin injections day after day to stay alive and well.

Those patients are responding to a series of reports of progress at Faustman's laboratory against type 1 diabetes, in which the immune system destroys insulin-producing islet cells. Type 1 diabetes generally appears early in life and is much more difficult to treat than type 2 diabetes, in which the body's insulin production gradually declines.

Insulin, a hormone, is needed to carry sugar from the bloodstream to the body's cells, which use the sugar -- called glucose -- for energy.

The Massachusetts researchers' first step in the mice study was to stop the immune system attack on islet cells with injections of TNF-alpha, a naturally occurring protein that destroys the wayward immune system cells.

Then they injected spleen cells from healthy mice into the diabetic mice who had been treated with TNF-alpha. The spleen cells were used because they carry proteins that play a key role in teaching new immune cells to recognize normal tissue.

The idea was that the spleen cells would halt the autoimmune attack, so that transplants of islet cells would restore insulin production. But then came a huge surprise. No transplants were needed, because insulin started to be produced by normal islet cells that unexpectedly appeared in the mice.

Some of those insulin-producing cells appeared as the few remaining islet cells in the mice multiplied -- a regeneration process that was something of a surprise to the researchers.

But there was an even bigger surprise. Some of the injected spleen cells had transformed into islet cells, "which was kind of amazing to us," Faustman says.

The transformation could help explain the very existence of the spleen, she says. The organ, which acts as a filter against foreign organisms that infect the bloodstream, is not considered essential. People can live without a spleen because its function can be taken over by other organs.

The important fact, Faustman says, is that adult cells can undergo this kind of transformation and regeneration, which has also recently been seen in other tissues, most notably nerve cells.

So the idea of re-educating the immune system not to attack friendly tissue and then regenerating cells to restore normal function could be applied to other autoimmune diseases such as rheumatoid arthritis and multiple sclerosis -- if the money was there, Faustman says.

One reason why money is needed is that TNF-alpha "is not a drug that is on the market," she says. "There is no validated manufacturing technique. It would cost $5 million to $10 million to establish one."

The American Diabetes Society would seem a natural source of funding, but "their grants are generally in the neighborhood of $100,000 or $200,000 a year," she says. There are hopes for support from the federal government or the pharmaceutical industry.

"Money could really move this forward," Faustman says. "Massachusetts General Hospital is trying all angles to get support for clinical trials."

More information

The Iacocca Foundation offers information on diabetes research. The American Diabetes Association has plenty of information about the disease.

SOURCES: Denise L. Faustman, M.D., Ph.D, director, Massachusetts General Hospital's Immunobiology Laboratory, Boston; Nov. 14, 2003, Science
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