Type 1 diabetes reversed in mice

Type 1 diabetes reversed in mice

Using gene therapy, researchers in the US managed to reverse Type 1 diabetes in laboratory mice, raising hope that a "cure" for the disease might be developed using this approach. However, only about 50 per cent of the treated mice responded to the therapy, so there is still a lot of work to do before such a method can be trialled as a potential treatment.

The researchers, from Baylor College of Medicine in Houston, Texas, presented the results of their experimental cure in a mouse model of Type 1 diabetes at The Endocrine Society's 92nd Annual Meeting in San Diego, on Sunday. The study was funded by the National Institute of Diabetes, Kidney and Digestive Diseases.

One of the team, Dr Lawrence Chan, chief of Baylor's diabetes, endocrinology and metabolism division, told the press that:

"A single treatment cured about 50 per cent of the diabetic mice, restoring their blood sugar to normal so that they no longer need insulin injections."

Type 1 diabetes mellitus (sometimes called juvenile diabetes), affects about 1 in 400 to 600 children and adolescents. It is thought to occur when the body's own immune system attacks and destroys the insulin-producing beta cells of the pancreas, resulting in near complete absence of insulin, the hormone that controls blood sugar. With insufficient insulin, levels of blood sugar build up and the result is diabetes.

Chan and colleagues developed a gene therapy to target two defects behind Type 1 diabetes: autoimmune attack and destruction of the beta cells, and tested it on nonobese diabetic mice which spontaneously develop diabetes due to autoimmunity, in the same way that humans with Type 1 diabetes do.

In previous studies they had shown that their new gene therapy stimulated new beta cell production in the liver, and restored insulin and normal blood sugar in over 100 mice that they had treated with chemicals to develop diabetes.

But when they tried the new gene therapy in nonobese diabetic mice with Type 1 diabetes, the treatment failed because the animals' immune systems destroyed the newly formed beta cells.

Chan explained that they then added a new feature to the therapy, "a protective gene that shields the newly formed beta cells from autoimmune attack".

The added gene was for interleukin-10, an anti-inflammatory cytokine that plays a key role in controlling the immune system; it has been shown to prevent diabetes developing in mice but it can't reverse the disease once it is under way because of the lack of beta cells.

So they added interleukin-10 to the gene therapy in one single injection in the mice, and after 20 months, they found that half the mice had undergone a complete reversal of their diabetes.

Chan said the therapy did not reverse autoimmunity in the whole of the body, but enough to protect the newly formed beta cells.

He likened the effect of adding interleukin-10 to giving the beta cells a "protective moat".

"We are now developing other strategies to try to fortify the newly formed beta cells and give them better weapons in addition to the moat, in order to increase the treatment's cure rate," said Chan.

The researchers are somewhat mystified as to why the therapy did not work in all the mice.

However, they said the treated mice that did not undergo a reversal of their diabetes put on weight and lived a little longer than their untreated counterparts.

Source: Endocrine Society.

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