“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 Laura Solt, Ph.D., a TSRI biologist who was the lead author of the study.
Type 1 diabetes is a consequence of the autoimmune destruction of insulin-producing beta cells in the pancreas. While standard treatment for the disease aims to replace lost insulin, the new study focuses instead on the possibility of preventing the initial devastation caused by the immune system—stopping the disease before it even gets started.
In the study, published in the March 2015 issue of the journal Endocrinology, the scientists 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 (Th17) of immune cells 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 Solt. “We were right.”
The researchers found SR1001 eliminated the incidence of diabetes and minimized insulitis, which is the inflammation associated with, and destroyer of, insulin-producing cells, in the treated animals. 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.
Solt notes that the study strongly suggests that 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.
Other authors of the study, “ROR Inverse Agonist Suppresses Insulitis and Prevents Hyperglycemia in a Mouse Model of Type 1 Diabetes,” include Subhashis Banerjee, Sean Campbell and Theodore M. Kamenecka of The Scripps Research Institute, and Thomas Burris of Saint Louis University School of Medicine. For more information on the study, see http://press.endocrine.org/doi/pdf/10.1210/en.2014-1677
This work was supported by National Institutes of Health (grants DK080201, MH092769 and DK089984) and a National Research Service Award (DK088499).
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
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