Reprogramming cells with gene therapy could help treat diabetes

by Barbara Hewitt on January 10, 2018

Gene therapy has the ability to restore normal blood glucose levels in people with type 1 diabetes by reprogramming cells to produce insulin, new research has found.

Scientists in the United States have successfully restored normal blood glucose levels in mice with type 2 diabetes and say it shows that a gene therapy approach can work.


The plan is to carry on with animal experiments but the team from the University of Pittsburgh School of Medicine believe that a clinical trial in humans with type 1 and type 2 diabetes in the near future is possible.

In type 1 diabetes the immune system attacks and destroys insulin producing beta cells in the pancreas, resulting in high blood levels of glucose. One fundamental goal of diabetes treatment is to preserve and restore functional beta cells, thereby replenishing levels of a hormone called insulin, which moves blood glucose into cells to fuel their energy needs.

But 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 potential solution to this problem is to reprogramme other cell types into functional beta like cells, which can produce insulin but are distinct from beta cells and therefore are not recognised or attacked by the immune system.

In this study the researchers used an adeno-associated viral (AAV) vector to deliver two proteins to the mouse pancreas, which reprogrammed plentiful alpha cells into functional, insulin producing beta cells.

‘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,’ said senior study author George Gittes of the University of Pittsburgh School of Medicine.

‘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,’ he added.

The goal was to generate functional beta like cells from pancreatic alpha cells, which may be the ideal source for beta cell replacement. For example, alpha cells are plentiful, resemble beta cells, and are in the correct location, all of which could facilitate reprogramming.

By comparing the gene expression patterns of normal beta cells and insulin producing cells derived from alpha cells, the researchers confirmed nearly complete cellular reprogramming. This gene therapy approach restored normal blood glucose levels in diabetic mice for an extended period of time, typically around four months, and the new insulin producing cells derived almost exclusively from alpha cells. Moreover, the strategy successfully generated functional insulin producing cells from human alpha cells.

‘The viral gene therapy appears to create these new insulin producing cells that are relatively resistant to an autoimmune attack. This resistance appears to be due to the fact that these new cells are slightly different from normal insulin cells, but not so different that they do not function well,’ Gittes explained.

He pointed out that several features of this approach could facilitate translation to humans. For one, AAV vectors like those used in this study are currently undergoing various gene therapy trials in humans. Moreover, the viral vectors can be delivered directly to the human pancreas through a routinely performed non-surgical endoscopic procedure. However, this procedure can elicit pancreatic inflammation. In addition, no immunosuppression is required, so patients would avoid related side effects such as an increased risk of infection.

However, one major concern was that the mice did eventually return to the diabetic state, suggesting that this treatment would not represent a definitive cure for the disease. ‘The protection from recurrent diabetes in the mice was not permanent, although some studies would suggest that processes in mice are highly accelerated, so four months in mice might translate to several years in humans,’ Gittes said.

‘If we are able to show efficacy in non-human primates, we will begin work with the FDA to get approval for the use of this viral gene therapy in diabetic patients, both type 1 and type 2,’ he added.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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