Type 1 diabetes is a chronic disease in which the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. A study published January 4th in Cell Stem Cell 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 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.
“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,” says 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.”
Approximately 9% of the world’s adult population has diabetes, which can cause serious health problems such as heart disease, nerve damage, eye problems, and kidney disease. 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 reprogram other cell types into functional beta-like cells, which can produce insulin but are distinct from beta cells and therefore are not recognized or attacked by the immune system. To explore the feasibility of this approach, Gittes and first author Xiangwei Xiao of the University of Pittsburgh School of Medicine engineered an AAV vector to deliver to the mouse pancreas proteins called Pdx1 and MafA, which support beta cell maturation, proliferation, and function. 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,” Gittes says. “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.”
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 says.
Currently, the researchers are testing their approach in primates. “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,” Gittes says.
The Latest on: Type 1 diabetes
Can diabetes affect muscle health?
on April 18, 2018 at 3:45 pm
Washington D.C. , Apr 18 : Even active youngsters with Type 1 diabetes can have muscle complications, finds a study. The research team from McMaster and York universities analysed muscle biopsies of young adults with and without Type 1 diabetes who exceed ... […]
Artificial pancreas is a safe and effective treatment for type 1 diabetes
on April 18, 2018 at 3:34 pm
Use of an artificial pancreas is associated with better control of blood sugar levels for people with type 1 diabetes compared with standard treatment, finds a review of the available evidence published by The BMJ today. The findings show that artificial ... […]
Class of type 2 diabetes drugs doesn't cut death risk compared to placebo
on April 18, 2018 at 9:24 am
Metformi is the most commonly prescribed drug type 2 diabetes and first on the market for the condition, but the drug sometimes doesn't work or triggers side effects. GLT-2 inhibitors increase the amount of sugar excreted by the body, and GLP-1 agonists ... […]
Two New Drug Classes Tied to Better Survival in Type 2 Diabetes
on April 18, 2018 at 8:31 am
Patients with type 2 diabetes who did not achieve adequate glycemic control with metformin had improved survival during follow-up if they received add-on therapy with a sodium-glucose cotransporter 2 (SGLT-2) inhibitor or a glucagon-like peptide 1 (GLP-1 ... […]
Type 1 Diabetes May Affect Muscle Health in Young Adults
on April 18, 2018 at 8:03 am
Active young adults with type 1 diabetes may experience poor muscle health, finds a study from McMaster University and York University, both in Ontario, Canada. Results of this study were published in Diabetologia, the journal of the European Association ... […]
Type 2 diabetes: Late breakfast could drive obesity
on April 18, 2018 at 7:05 am
It is sometimes thought that people with type 2 diabetes may develop type 1. Learn why some people with type 2 diabetes may be called insulin dependent. Read now It is sometimes thought that people with type 2 diabetes may develop type 1. Learn why some ... […]
Add Muscle Weakness as Another Cost of Type 1 Diabetes
on April 18, 2018 at 6:36 am
WEDNESDAY, April 18, 2018 (HealthDay News) -- Poor muscle health may be a complication of type 1 diabetes, even in young people who get plenty of exercise. That's the finding of Canadian researchers who analyzed muscle samples from young adults with and ... […]
Study finds muscle complications among active young adults with Type 1 diabetes
on April 18, 2018 at 12:50 am
A new study from McMaster and York universities has found that poor muscle health may be a complication of Type 1 diabetes, even among active twenty-somethings. The research team analyzed muscle biopsies of young adults with and without Type 1 diabetes who ... […]
Active young adults with Type 1 diabetes have muscle complications: study
on April 17, 2018 at 11:23 pm
Thomas Hawke, corresponding author of the study and a professor of pathology and molecular medicine at McMaster University. Credit: McMaster University A new study from McMaster and York universities has found that poor muscle health may be a complication ... […]
Study: Hot spots of type 1 diabetes found in food swamps
on April 17, 2018 at 7:34 pm
Hot spots of type 1 diabetes in New York City are found in food swamps, areas with a higher proportion of fast food restaurants, for children and adults with type 1 diabetes according to a new study published in the Endocrine Society's Journal of the ... […]
via Google News and Bing News