Gene therapy temporarily halts type 1 diabetes in mice

A gene therapy has been used to restore normal blood sugar levels in mice with type 1 diabetes, according to a study published this month in the journal Cell Stem Cell.

In type 1 diabetes the immune system destroys beta cells, but not alpha cells, in the pancreas. A team at the University of Pittsburgh School of Medicine and the Children's Hospital of Pittsburgh attempted to turn alpha cells into beta cells, in order to produce insulin. 

'If you gave patients new insulin cells with a transplant, it will kill them off. If we use gene therapy to get the body to make new insulin-producing cells in the body, logically it should attack those cells too,' explained Dr George Gittes, a lead study author and pediatric surgeon at the University of Pittsburgh, to Gizmodo.

But their treatment was successful in mice, at least temporarily. They used an adeno-associated virus, the standard gene therapy technology, to deliver two proteins, Pdx1 and MafA, to the pancreas of a mouse. This reprogrammed alpha cells into beta cells. Normal blood sugar levels were restored in the diabetic mice. However, this effect only lasted for around four months, though this would likely translate to years in humans.

'This study is essentially the first description of a clinically translatable, simple single intervention in autoimmune diabetes that leads to normal blood sugars,' said Dr Gittes. Additionally, many treatments targeting autoimmune disorders such as diabetes depress the immune system, causing lifelong risks. This treatment doesn't – a key advantage.

The gene therapy has only been tested on mice so far, but future work will be carried out in primates, and the group hopes to gain approval from the US Food and Drugs Administration (FDA) for clinical trials in humans. It is a promising new approach to tricking the immune system and alleviating the symptoms of diabetes. 

At present, type 1 diabetes has no cure, and is managed with a lifetime of insulin injections. Insulin is a hormone produced by pancreatic beta cells, which drives glucose absorption, lowering its levels in the body. 

The finding it is the latest of a string of promising developments in gene therapy. In October, the FDA approved Spark Therapeutics's gene therapy for a rare form of inherited blindness (see BioNews 922). The month also saw successful human trials on haemophilia A (see BioNews 931) and haemophilia B (see BioNews 930).