Diabetes Cure 'In Sight After Major Breakthrough'
posted 11/25/03
Injection Leads to Islet Regeneration in Autoimmune Diabetes. A possible cure for insulin-dependent diabetes is in sight following a major medical breakthrough. Scientists in the United States have not only halted the disease in mice mimicking human type 1 diabetes, but reversed it.

Plans are now under way to conduct patient trials which, could lead to the first ever curative treatment for the disorder. Massachusetts General Hospital researchers have harnessed newly discovered cells from an unexpected source, the spleen, to cure juvenile diabetes in mice, a surprising breakthrough that could soon be tested in local patients and open a new chapter in diabetes research.

The current study builds on the team's earlier work in which they found that beta cell-directed autoimmunity in NOD mice could be reversed and pancreatic islet cell function could be restored by injection of donor splenocytes and complete Freund's adjuvant, which induces expression of tumor necrosis factor (TNF)-alpha.

The MGH scientists injected diabetic mice with the spleen cells. The cells migrated to their pancreases, prompting the damaged organs to regenerate into healthy, insulin-making organs, ending their diabetes.

This is among the few documented cases of a major organ regenerating itself in an adult mammal. The research also finds a potential use for the spleen, long considered an organ with no apparent purpose.

"This shows there might be a whole new type of therapy that we haven't tapped into," said Dr. Denise Faustman, MGH immunology lab director and lead author of the new study, which appears today in the journal Science. "We've figured out how to regrow an adult organ."

Dr. George King, Joslin Diabetes Center research director, who was not involved in the research, said: "That you could just take spleen cells, infuse them, and somehow the pancreas is regenerated, that's exciting . . . The next step is to see if it can be done in humans."

Mass. General's Diabetes Center has received approval from the US Food and Drug Administration to try the techniques pioneered by Faustman in humans. The center's director, Dr. David M. Nathan, stressed it remains uncertain whether they will work in humans.

The hospital's team has not yet raised enough money to proceed with a 40-person clinical trial, which Nathan estimates would cost about $10 million.

The research was funded by the Boston-based Iacocca Foundation, a diabetes charity begun by then-Chrysler executive Lee Iacocca two decades ago after his wife succumbed to the disease. The foundation's resources are not nearly enough to bankroll the proposed clinical trial.

In juvenile, or Type 1, diabetes, victims' immune systems attack the insulin-making cells in the pancreas early in life. Insulin moves sugar, a crucial energy source, from blood into cells.

The new MGH findings build on research first reported two years ago, when Faustman's team found it could retrain the immune system of diabetic mice not to attack the pancreas by injecting the mice with spleen cells, along with a protein that tames the immune system, from healthy mice.

Faustman's team expected to have to transplant new insulin-making cells into the pancreas to give the mice the lifetime ability to produce insulin. In humans, such transplants are risky and debilitating surgeries.

Instead, it turned out that a select subpopulation of the spleen cells grew and nurtured the damaged pancreases into health. The pattern repeated in 11 mice.

"We've found that [pancreas] regeneration was occurring and that cells were growing from both the recipient's own cells and from the donor cells," Faustman said.

The results, published in the journal Science, confirmed that the pancreas was being reconstructed in the sick mice. That finding means for the first time there is a prospect of curing patients with type 1 diabetes.

Source: Diabetes In Control.com: Science 2003;302:1223-1227.

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