Type 1 diabetes is a genetic disease caused when a person's immune system attacks and destroys the pancreatic beta cells responsible for creating insulin in the body, eventually eliminating insulin production entirely. Standard treatment for the disease aims to replace the lost insulin.
Laura Solt is a biologist at The Scripps Research Institute's Florida campus.
However, a team of scientists from Scripps Florida, led by TSRI biologist Laura Solt have identified a synthetic compound that may prevent the initial devastation of the insulin-producing cells – stopping the disease before it begins.
“The animals in our study never developed high blood sugar indicative of diabetes, and beta cell damage was significantly reduced compared to animals that hadn’t been treated with our compound,” said Dr. Solt.
According to the Centers for Disease Control and Prevention, approximately 29.1 million Americans have diabetes. A majority of these cases are type 2 diabetes, a metabolic disorder that can begin at any age and results in a shortage of insulin, rather than the complete lack of insulin caused by type 1. Both types of diabetes can lead to a number of comorbidities over a patient's lifetime, potentially resulting in death.
In the new study, the TSRI team tested an experimental compound known as SR1001 in non-obese diabetic animal models. The compound targets a pair of “nuclear receptors” (RORα and RORg) that play critical roles in the development of a specific population of immune cells (Th17) associated with the disease.
“Because Th17 cells have been linked to a number of autoimmune diseases, including multiple sclerosis, we thought our compound might inhibit Th17 cells in type 1 diabetes and possibly interfere with disease progression,” said Dr. Solt. “We were right.”
The researchers found that, in the treated animals, SR1001 eliminated the incidence of diabetes and minimized insulitis, which is the inflammation associated with, and the destroyer of, insulin-producing cells. The compound suppressed the immune response, including the production of Th17 cells, while maintaining normal insulin levels. It also increased the frequency of the expression of Foxp3 in T cells, which controls the development and function of a type of immune cell known as T regulatory cells.
Dr. Solt notes that the study strongly suggests Th17 cells have a pathological role in the development of type 1 diabetes, and use of ROR-specific synthetic compounds targeting this cell type may have potential as a preventative therapy for type 1 diabetes. “It certainly opens the door for other areas to be looked at,” she said.