Gene therapy of diabetes and obesity
Researchers at the University of Barcelona, working under the guidance of Professor Fatima Bosch, cured obesity and type 2 diabetes in mouse models using gene therapy that induces the synthesis of fibroblast growth factor-21 (FGF21) in various tissues.
Fibroblast growth factor-21 is a hormone secreted by a number of organs and necessary for many tissues to maintain normal energy metabolism. Fibroblast growth factor-21, produced by living organisms, is rapidly destroyed when administered by traditional methods. Therefore, pharmaceutical companies have developed analogues and mimetics (substances similar to natural ones) of this hormone and have already successfully conducted their clinical studies. However, in order to obtain clinical results, these drugs require regular administration, while they can cause immunological reactions associated with the introduction of foreign proteins.
The vector proposed by the authors based on an adenoassociated virus carrying the fibroblast growth factor-21 gene, on the contrary, provides a long-term synthesis of this hormone in the body after a single injection of a gene therapy drug.
The therapy has been successfully tested on two different mouse models of obesity and accompanying type 2 diabetes mellitus. In one case, obesity was induced by diet, and in the other by mutations.
After the introduction of the vector, the animals' body weight decreased, the accumulation of fat in the body decreased and the severity of inflammation in adipose tissue decreased. In addition, they disappeared manifestations of steatosis (fatty degeneration), inflammation and liver fibrosis. All this ensured increased sensitivity of tissues to insulin and healthy aging of animals without any undesirable side effects.
The obtained results were reproduced using genetic manipulations on three different tissues (liver, adipose tissue and skeletal muscles). This flexibility of therapy greatly expands the possibilities of its application, as it allows you to choose the most suitable target tissue in each case. Subsequently, the fibroblast growth factor-21 synthesized by one of these tissues spreads with blood flow throughout the body.
In addition to mouse models of obesity, the authors introduced a therapeutic vector to a group of healthy animals. This prevented age-associated weight gain and the development of tissue resistance to insulin, thus contributing to healthy aging.
In addition, the observations carried out by the authors showed that the use of gene therapy reduces the risk of liver tumors associated with prolonged maintenance of animals on a hypercaloric diet.
The importance of the results obtained is due to the rapidly increasing incidence of obesity and type 2 diabetes worldwide. The authors note that obesity increases the risk of mortality and in itself is an important risk factor for the development of diseases of the cardiovascular and immune systems, hypertension, arthritis, neurodegenerative diseases and some types of cancer.
The next stage of the work will be conducting preclinical studies on larger animals, after which you can proceed to planning clinical trials. The developers are determined to succeed, as gene therapy using vectors based on an adeno-associated virus has already been approved in Europe and the USA for the treatment of a number of diseases.
The article by Veronica Jimenez et al. FGF21 gene therapy as treatment for obesity and insulin resistance is published in the journal EMBO Molecular Medicine.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Barcelona: UAB researchers cure type 2 diabetes and obesity in mice using gene therapy.