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Headlines > Preclinical Research

Mice tests reveal scope for diabetes cure

By Wai Lang Chu , 04-May-2006

Scientists believe they have made a major breakthrough in a potential cure for diabetes after animal experiments using a combinatorial treatment approach reversed onset type 1 diabetes.

While human clinical trials are planned later this year, the news is encouraging because if successful in humans, the replacement of current insulin-injection treatments altogether is possible.

Type 1 diabetes, also called insulin-dependent diabetes or juvenile diabetes, occurs when the immune system mistakenly destroys the insulin-producing beta cells of the pancreas, which are key to controlling blood sugar levels.

As a result, type 1 diabetes sufferers inject insulin daily to control blood sugar levels. However, complete control is difficult to achieve and damage to body organ systems can still occur.

Complications from type 1 diabetes can include kidney failure, adult blindness and the need for amputations.

The study involved combining two therapies, anti-CD3 antibody and proinsulin peptide, which had already been tested individually in human clinical trials.

The data obtained demonstrated better efficacy, longer-lasting results and fewer side effects in the preclinical trials in mice than either therapy has shown alone in the human studies.

"The finding of increased efficacy of reversal of recent-onset type 1 diabetes in animals that received a combination of systemic anti-CD3 antibody and intranasal proinsulin peptide compared to therapy with the antibody alone is an exciting and important finding," said Richard Insel, Executive Vice President for Research at the Juvenile Diabetes Research Foundation.

The anti-CD3 antibody has been shown to temporarily reverse recent onset human type 1 diabetes in two independent clinical trials. The reversal was maintained for more than a year.

"This combination approach is worth evaluating in human type 1 diabetes to increase both the overall efficacy of the treatment and the duration of the beneficial effect," Insel said.

Study leader, Matthias von Herrath's approach focuses on teaching the immune system to tolerate, rather than attack, the insulin-producing beta cells of the pancreas.

By injecting the anti-CD3 antibody, which calms the immune system and lessens the attack on the beta cells, along with a piece of the nasal proinsulin peptide, which acts like a vaccine and induces a special cell type called "regulatory cells" that can actively and highly specifically protect beta cells.

von Herrath was able to stop the immune system's destruction of the beta cells in mice.

"The combinatorial approach doubled the efficacy in laboratory mice, with fewer side effects than using either one alone," he said.

The study represents the first time a combinatorial treatment approach using a vaccine strategy had ever been tried in type 1 diabetes. von Herrath added that the combined therapy also showed long-lasting results as the diabetes never reoccurred in the lifespan of the mice.

He also said the human clinical trials, which still require regulatory approval, would be directed at persons recently diagnosed with type 1 diabetes or who are already being treated for pre-diabetes.

The finding was published in the online version of the >Journal of Clinical Investigation in the paper: "A novel combination therapy in recent onset autoimmune diabetes: synergy of anti-CD3 and nasal proinsulin to induce Tregs."

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