Researchers cure type 2 diabetes and obesity in mice using gene therapy

July 10, 2018, Autonomous University of Barcelona
The research team at CBATEG (UAB). Credit: UAB

A research team from the UAB led by Professor Fatima Bosch has managed to cure obesity and type 2 diabetes in mice using gene therapy.

A single administration of an adeno-associated viral vector (AAV) carrying the FGF21 (Fibroblast Growth Factor 21) gene, resulted in genetic manipulation of the liver, adipose tissue or to continuously produce the FGF21 protein. This protein is a hormone secreted naturally by several organs that acts on many tissues for the maintenance of correct energy metabolism. By inducing FGF21 production through gene therapy the animal lost weight and decreased , which causes the development of type 2 diabetes.

The therapy has been tested successfully in two different mouse models of obesity, induced either by diet or genetic mutations. In addition, the authors observed that when administered to healthy mice, the gene therapy promoted healthy ageing and prevented age-associated weight gain and insulin resistance.

After treatment with AAV-FGF21, mice lost weight and reduced fat accumulation and inflammation in adipose tissue; fat content (steatosis), inflammation and fibrosis of the liver were also reversed; this led to an increase in insulin sensitivity and in healthy ageing, without any adverse side effects.

The results have been reproduced after genetic manipulation of three different tissues (liver, adipose tissue or skeletal muscle) to produce the FGF21 protein. "This gives a great flexibility to the therapy, since it allows to select each time the most appropriate tissue, and in case some complication prevents manipulating any of the tissues, it can be applied to any of the others. When a produces FGF21 protein and secretes it into the bloodstream, it will be distributed throughout the body," says the director of the study Dr. Fatima Bosch.

The authors highlight the importance of these results, since "the prevalence of type 2 diabetes and obesity is growing at alarming rates around the world," explains the UAB researcher and co-author of the study Claudia Jambrina. Obesity also increases the risk of mortality and represents an important risk factor for cardiovascular and immune diseases, hypertension, arthritis, neurodegenerative disorders and some types of cancer.

"This is the first time that long term reversion of obesity and insulin resistance have been achieved upon a one-time administration of a gene therapy, in an animal model that resembles obesity and type 2 diabetes in humans," says the first author of the paper and UAB researcher Veronica Jimenez. "The results demonstrate that it is a safe and effective therapy."

The results also reveal that the administration of the gene therapy protected against the risk of tumor formation in the liver in response to a hypercaloric diet for a prolonged period of time.

The native FGF21 protein has a short half-life when administered using conventional procedures. For this reason, the pharmaceutical industry has developed FGF21 analogues/mimetics and has already conducted clinical trials. FGF21 analogues/mimetics, however, require periodic administration to mediate clinical benefits, but may raise immunological issues associated to the administration of exogenous proteins. The gene therapy vectors used by Dr. Bosch's team, however, induce the mice to produce for many years the same FGF21 hormone naturally produced by the body, after a single administration and without any adverse effects.

For Dr. Bosch the next step will be to "test this therapy in larger animals before moving to clinical trials with patients." AAV-mediated has been approved in Europe and the United States for the treatment of several diseases, due to its efficacy and safety profile. Similarly, there exists extensive clinical experience in applying AAV-mediated gene transfer to liver and skeletal muscle. Consequently, "the described in this study constitutes the basis for the future clinical translation of FGF21 gene transfer to treat type 2 diabetes, obesity and related comorbidities," Dr. Bosch concludes.

The results of the research are published today in EMBO Molecular Medicine.

Explore further: Research reveals potential target for alcohol liver disease

More information: Veronica Jimenez et al, FGF21 gene therapy as treatment for obesity and insulin resistance, EMBO Molecular Medicine (2018). DOI: 10.15252/emmm.201708791

Related Stories

Research reveals potential target for alcohol liver disease

August 21, 2017
Drinking too much alcohol can damage the liver, but investigators have discovered a protective response in the organ that might be targeted to help treat alcoholic liver disease. The team—led by researchers at Beth Israel ...

Tweaking muscle metabolism prevents obesity and diabetes in mice

June 28, 2017
Mildly stressing muscle metabolism boosts levels of a beneficial hormone that prevents obesity and diabetes in mice, according to a new study by researchers at the University of Iowa.

Life-extending hormone bolsters the body's immune function

January 11, 2016
A hormone that extends lifespan in mice by 40% is produced by specialized cells in the thymus gland, according to a new study by Yale School of Medicine researchers. The team also found that increasing the levels of this ...

Hormone may help fight obesity and reduce cholesterol

September 3, 2013
Research has shown that giving obese rodents a recently identified circulating protein called fibroblast growth factor 21 (FGF21) helps improve their metabolism. Now investigators reporting in the Cell Press journal Cell ...

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

Gene that makes humans eat more sugar can also lower body fat

April 10, 2018
You are what you eat, the old saying goes. But it turns out that may be backwards. What if, in fact, you eat certain things because of who you are? Scientists have known since 2013 that a common version of the gene FGF21 ...

Recommended for you

Switching to certain antidiabetic drugs linked to increased risk of major complications

July 18, 2018
For people with type 2 diabetes, switching to sulfonylurea drugs to control blood sugar levels is associated with an increased risk of complications compared with staying on the drug metformin, finds a study in The BMJ today.

Researchers cure type 2 diabetes and obesity in mice using gene therapy

July 10, 2018
A research team from the UAB led by Professor Fatima Bosch has managed to cure obesity and type 2 diabetes in mice using gene therapy.

Human clinical trial reveals verapamil as an effective type 1 diabetes therapy

July 9, 2018
Researchers at the University of Alabama at Birmingham Comprehensive Diabetes Center have discovered a safe and effective novel therapy to reduce insulin requirements and hypoglycemic episodes in adult subjects with recent ...

New targets found to reduce blood vessel damage in diabetes

July 9, 2018
In diabetes, both the tightly woven endothelial cells that line our blood vessels and the powerhouses that drive those cells start to come apart as early steps in the destruction of our vasculature.

Insurance gaps linked to five-fold rise in hospital stays for adults with type 1 diabetes

July 9, 2018
For a million American adults, living with type 1 diabetes means a constant need for insulin medication, blood sugar testing supplies and specialized care, to keep them healthy and prevent a crisis that could end up in an ...

Abnormal branched-chain amino acid breakdown may raise diabetes risk

July 5, 2018
In the U.S., about five out of 100 expectant mothers develop gestational diabetes mellitus (GDM), a temporary form of diabetes in which hormonal changes disrupt insulin function. Although GDM is often symptomless and subsides ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym568933
not rated yet Jul 17, 2018
I was diabetic for 13 years and was taking metformin 1000 mg twice daily. Last A1C was 15. My symptoms have always been stomach and bowels. I am a 54 year old male. the metformin wasn't really working so this year, our family doctor started me on Natural Herbal Gardens Diabetes Disease Herbal mixture, With the help of Natural Herbal Garden natural herbs I have been able to reverse my symptoms using herbs, my symptoms totally declined over a 7 weeks use of the Natural Herbal Gardens Diabetes disease natural herbal formula. My diabetes is totally reversed! Visit their website www . naturalherbalgardens . com I am thankful to nature

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.