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Can Immune Treatment Cure Diabetes?

Type 1 Diabetes Immune Dysfunction May Be Treatable
By
WebMD Health News
Reviewed by Louise Chang, MD

June 25, 2007 (Chicago) -- With increasing optimism, scientists report progress in immune therapies that could stop type 1 diabetes in its tracks.

Type 1 diabetes is an autoimmune disease. This means that the body's powerful immune responses -- designed for protection against infectious diseases and cancers -- turn on the body itself.

When anti-self immune responses destroy the insulin-producing beta cells of the pancreas, diabetes is the inevitable result. Scientists have known this for many years. But they have never found a way to call off the dogs. Yet.

It's possible that immune treatments trials now under way could find the "off" switch to diabetes autoimmunity. Researchers reported progress at the American Diabetes Association's 67th Annual Scientific Sessions, held June 22-26 in Chicago.

Teaching Tolerance to Haywire Immune Responses

Diabetes anti-self immune responses often have a specific target -- a pancreatic enzyme called GAD. A vaccine called Diamyd incorporates an artificial GAD protein. The idea is to induce immune tolerance to GAD.

Immune tolerance is a natural process. But it's been immensely hard for researchers to induce it. The idea is to expose a person to just enough of a substance to help the immune system recognize it as normal. If too little is used, nothing happens. If too much is used, it can trigger even more harm.

Ake Lernmark, PhD, of the University of Washington in Seattle and Lund University in Malmo, Sweden, noted that clinical studies seem to have identified just the right dose of Diamyd to induce GAD tolerance.

Trials suggest that the vaccine may be able to stop autoimmune destruction of insulin-producing pancreatic beta cells.

Diamyd "has a clear and statistically significant protective effect on residual insulin function," Lernmark said. "It is effective, safe, and easily administered."

Unfortunately, a recent clinical trial of Diamyd had to be stopped when investigators somehow got doses of the real vaccine mixed up with doses of inactive placebo. A new phase III clinical trial is now enrolling patients.

Switching Targets in Midstream

The breakthrough in diabetes immune therapy may come from left field -- that is, from the field of multiple sclerosis.

Northwestern University researcher Stephen D. Miller, PhD, usually works on autoimmune responses in multiple sclerosis. But his team's findings appear extremely relevant to diabetes.

The basic problem with teaching tolerance to self-reactive immune responses, Miller finds, is that once these immune responses become tolerant to one self target, they find a new self target.

That helps explain a lot of immunologists' frustration. Fortunately, Miller and colleagues find that it's possible to stay one step ahead of the immune system. Anti-self immune responses, Miller reports, tend to follow predictable patterns.

By using spleen cells to carry specific target peptides (protein building blocks) to the immune system, Miller's team has stayed one step ahead of the autoimmune process.

"Tolerance can be induced using spleen cells coupled with a cocktail of peptides," he says. "This is a very effective way to induce tolerance."

Animal tests are under way to see whether this concept works for diabetes. Meanwhile, Miller's team is planning early clinical trials of the approach in multiple sclerosis.

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