CRISPR, which stands for “Clustered Regularly Interspaced Short Palindromic Repeats”, is a gene editing tool that can cut, insert and correct DNA within a cell. With precision, it can remove a defective gene or insert a good one, enabling it to correct a genetic condition. There has been an influx of CRISPR studies lately and most of them have promising applications to treating genetic diseases (like Huntington’s disease, blood thalassemia, cystic fibrosis, hypertrophic cardiomyopathy, high cholesterol and cancers) and metabolic disorders like diabetes.
Diabetes (or hyperglycemia) is a condition wherein blood glucose levels in the body rise higher than normal levels. To control blood glucose levels, the body uses insulin (a hormone secreted by the pancreas) to turn glucose into energy. People with type 1 diabetes cannot produce insulin in their bodies because the pancreatic cells that produce insulin have been destroyed by their own immune system. On the other hand, people with type 2 diabetes are not producing enough insulin or have bodies that are not reacting to insulin properly. When the body has an abnormal response to insulin, this is called insulin resistance. A high insulin resistance is a risk factor for developing type 2 diabetes. In the US alone, 27 million people have type 2 diabetes.
The study is carried out by using skin cells from newborn mice. Researcher cultured the cells in the lab to make skin grafts. The skin cells were then edited with CRISPR to target a gene responsible for producing a hormone called GLP-1 (glucagon-like peptide-1). The skin grafts were then transplanted into mice with type 2 diabetes but with healthy immune systems.
The GLP-1’s main function in the body is to stimulate the release of insulin which in turn regulates blood glucose levels. One treatment regimen for type 2 diabetes is based on using injectable drugs that mimic the action of normal GLP-1 hormones. These drugs bind to GLP-1 receptors which then trigger the body to produce insulin, the same response triggered by normal GLP-1 hormones of the body. However, normal GLP-1 has a short half-life and, in effect, has a short period of effect.
To remove this setback, researchers edited the GLP-1 gene so that it will produce a GLP-1 hormone with longer effectivity. Results were promising: 80% of the skin grafts released the edited hormone and were effective in regulating blood glucose levels in mice, which were given high-fat diet, for more than four months. The mice showed less weight gain and reversed insulin resistance.
While the research is still at an early stage, researchers are hoping the study will be a leading tool for treating type 2 diabetes in human. One possibility lies in replacing repeated injections of drugs with skin grafts containing the edited GLP-1 gene. Researcher Xiaoyang Wu said, “We didn’t cure diabetes, but it does provide a potential long-term and safe approach of using skin epidermal stem cells to help people with diabetes and obesity better maintain their glucose levels.”
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