Gene Therapy Restores Normal Blood Glucose Levels in Mice With Type 1 Diabetes


Source: Cell Press

Summary: A new study demonstrates that a gene therapy approach can lead to the long-term survival of functional beta cells as well as normal blood glucose levels for an extended period of time in mice with diabetes.


Diabetes mellitus, a metabolic disease that affects approximately 9% of the world’s adult population. It can cause serious health problems such as heart disease, nerve damage, eye problems, and kidney disease. The basic goal of diabetes treatment is to restore the function of pancreatic beta cells. In Type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In patients with type 1 diabetes, beta-cell replacement therapy is likely doomed to failure because the new cells might fall victim to the same autoimmunity that destroyed the original cells. A new study demonstrates that a gene therapy approach can lead to the long-term survival of functional beta cells as well as normal blood glucose levels for an extended period of time in mice with diabetes. The study findings were published in the journal Cell Stem Cell.

Gene therapy is an experimental technique that uses genes to treat or prevent disease.

In these two microscopy images, human islets (the source of insulin cells) were poisoned with a drug to remove the insulin cells, and then treated with either an empty virus (left panel) or the therapeutic virus (right panel), and then grown in a diabetic mouse. The green staining on the right reflects abundant insulin cell in these islets. The blood sugar of the diabetic mice were made normal by the gene-therapy-treated human islets on the right. Credit: George Gittes and Xiangwei Xiao

The researchers used an adeno-associated viral (AAV) vector to deliver to the mouse pancreas two proteins, Pdx1 and MafA, which reprogrammed plentiful alpha cells into functional, insulin-producing beta cells. The goal was to generate functional beta-like cells from pancreatic alpha cells, which may be the ideal source for beta cell replacement. This gene therapy approach restored normal blood glucose levels in diabetic mice for an extended period of time, typically around 4 months, and the new insulin-producing cells derived almost exclusively from alpha cells. Several features of this approach could facilitate translation to humans. The protection from recurrent diabetes in the mice was not permanent, as the processes in mice are highly accelerated, so four months in mice might translate to several years in humans.

Senior study author, George Gittes said, “This study is essentially the first description of a clinically translatable, simple single intervention in autoimmune diabetes that leads to normal blood sugars, and importantly with no immunosuppression”, “A clinical trial in both type 1 and type 2 diabetics in the immediate foreseeable future is quite realistic, given the impressive nature of the reversal of the diabetes, along with the feasibility in patients to do AAV gene therapy.”


More Information: Xiao et al.: “Endogenous Reprogramming of Alpha Cells into Beta Cells, Induced by Viral Gene Therapy, Reverses Autoimmune Diabetes”, (2017). DOI: 10.1016/j.stem.2017.11.020


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