Gene therapy may reduce obesity, reverse type 2 diabetes
Researchers developed a gene therapy that specifically reduces fat tissue and reverses obesity-related metabolic disease in obese mice, according to a new study published in Genome Research.
To overcome the side effects of current anti-obesity drugs, researchers developed a specific gene silencing therapy against a fatty acid metabolism gene, Fabp4. Researchers used a clustered regularly interspaced short palindromic repeats (CRISPR) interference system wherein catalytically dead CRISPR associated protein 9 and single guide ribonucleic acid was targeted to white adipocytes with a tissue-specific fusion peptide.
The complex is internalized with little toxicity to the cells and upon internalization, the molecule complex decreases the expression of Fabp4 and reduces lipid storage in adipocytes. Demonstrating that this delivery method performed well in cells, researchers tested their therapy on obese mice. Mice were fed a diet high in fat leading to obesity and insulin resistance. Fabp4 repression resulted in a 20 percent reduction of body weight and improved insulin resistance and inflammation after just six weeks of treatment. Additional systemic improvements were observed, including a reduction in fatty lipid deposition in the liver and reduced circulating triglycerides.
The obesity epidemic affects nearly half a billion people worldwide, many of them children. Obesity-related diseases including heart disease, stroke, type 2 diabetes, and cancer are a leading cause of preventable death. Obesity is caused by both genetic and environmental factors, confounding the development of effective anti-obesity drugs, which exhibit severe off-target effects.
The current standard U.S. Food and Drug Administration-approved treatment showed just 5 percent of body weight loss after one year of treatment in humans. However, while this therapy displays promising results in mice, further studies are required before it can be used in clinical treatment against human disease. Importantly, this work highlights the advances in precision gene editing technology, which can be translated to other types of therapies.