Drug-Vaccine Combo Reverses Type 1 Diabetes in Mice

Results are promising but human studies are needed, researchers say

THURSDAY, April 20, 2006 (HealthDay News) -- By combining a vaccine and an immunosuppressant drug, U.S. researchers say they have successfully reversed type 1 diabetes in mice.

The promising combination treatment works twice as well as either treatment alone, according to researchers at the La Jolla Institute for Allergy and Immunology in San Diego.

The approach "will work best on recent-onset diabetes," said senior researcher Dr. Matthias von Herrath, a professor of immunology and allergy at the institute. He emphasized that the approach, if it continues to bear out, is still several years away from being available to type 1 diabetics. Clinical trials would have to be done, and they typically take several years.

The findings were published online Thursday prior to their inclusion in the May print issue of the Journal of Clinical Investigation.

About 5 percent of diabetics have type 1 disease, in which the immune system goes awry and destroys insulin-producing beta cells in the pancreas. The illness affects almost 20 million people worldwide, and by the time symptoms appear, nearly 80 percent of the beta cells are destroyed, von Herrath said.

In their study, the San Diego team gave mice a low-dose oral antibody called anti-CD3, which works systemically to prevent the destruction of beta cells. They also gave the mice a nasally administered pro-insulin peptide. This protein acts like a vaccine, working locally to protect the beta cells from being destroyed.

In previous studies, other researchers have showed that giving anti-CD3 to people who had just been diagnosed with diabetes could stop the destruction of beta cells for about a year and a half, von Herrath said. "That is very encouraging. But stopping the destruction temporarily is not enough."

He added that giving the antibody alone is not practical, because it has other side effects, such as activating viruses in the body. "The issue is, how can you balance?" von Herrath said.

His team turned to this combination approach instead. When they combined the treatments, overall side effects decreased but effectiveness increased.

"When you combine [the two treatments], they work very well," von Herrath said. "It has been historically in mice easy to prevent diabetes when you intervene early, but it has been very difficult to reverse diabetes in mice. We have reversed it, and for the first time tried the combination approach of a vaccine with very low side effects and a systemic immune modulator/suppressor."

Compared to giving the antibody alone, the combination therapy reversed diabetes in twice the number of mice, von Herrath said. "Over their lifespan [of about two years], it never came back. It didn't come back in any of them. They were already diabetic, and they came back to normal blood sugar levels," he said.

Clinical trials are needed to test the combination approach, he said. The treatment is likely to work best on people recently diagnosed with type 1 diabetes, as they are likely to have fewer beta cells destroyed.

The study is good news, said Dr. George Eisenbarth, director of the Barbara Davis Center for Childhood Diabetes at the University of Colorado, Aurora.

"There are two major parallel pathways to reverse or prevent [type 1] diabetes," he said. "This research merges the two pathways, finding they are synergistic."

The combo therapy achieved "good reversal" of disease, he noted, "better than either alone."

More information

For more on type 1 diabetes, head to the American Diabetes Association.

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