In a breakthrough discovery, Oregon State University scientists have uncovered a compound with the ability to block the development of type 1 diabetes in mice by minimizing inflammation of the pancreatic islets producing insulin. If the compound, nicknamed BBQ, has the same effect and low toxicity in humans, it could lead to an entirely new kind of therapy for type 1 diabetes with the potential to prevent the onset, or even cure, the disease.
The study, recently published in the Journal of Immunology, is titled “Activation of the Aryl Hydrocarbon Receptor by 10-Cl-BBQ Prevents Insulitis and Effector T Cell Development Independently of Foxp3+ Regulatory T Cells in Nonobese Diabetic Mice.”
According to a previous study published in the Journal of the American Medical Association (JAMA), titled “Prevalence of Type 1 and Type 2 Diabetes Among Children and Adolescents From 2001 to 2009“, the rate of newly diagnosed children with type 1 diabetes increased 21 percent between the years 2001–09. Juvenile diabetes differs from the adult-onset type 2 by an immune reaction that destroys insulin producing cells in the pancreas.
In earlier studies, the research team discovered that the compound dioxin prevents type 1 diabetes by binding to the aryl hydrocarbon receptor (AhR). Dioxin is not a suitable drug candidate, however, as it is highly toxic and accumulates in the body. “So we went looking for another compound that would function in the same way but without the bad effects,” said a co-researcher, Dr. Siva Kolluri, in a news release.
Researchers screened tens of thousands of chemicals, and at last succeeded in coming across a chemical producing the same results as dioxin, but without toxicity — BBQ. The compound binds to the AhR located on immune T-cells.
Scientists demonstrated that upon BBQ binding, the AhR moves to the nucleus of the cells. T-cells are crucial for orchestrating immune responses, and when the AhR binds to the cells’ DNA, it changes the expression of genes involved in the immune attack targeting the pancreatic insulin-producing cells.
The team used a mouse model that develops type 1 diabetes, treating half with BBQ three times per week. Unlike their untreated counterparts, the BBQ-treated mice did not develop diabetes, and the researchers noted there were virtually no signs of inflammation in the mice’s pancreas.
“This compound has a very targeted effect, and it’s safe at therapeutic doses in mice,” said Dr. Nancy Kerkvliet, lead study researcher. “If it works in human clinical studies, we envision a therapy that could be started early to block the onset of Type 1 diabetes, and maybe even cure it in the long run.”
According to Dr. Allison Ehrlich, a co-researcher, the beauty of BBQ is that it does not shut down the entire immune system. T-cells develop when they are exposed to pathogens or foreign cells; in this way, some cells become more specialized to carry out specific immune tasks. BBQ, through its binding to the AhR, prevents T-cells from going through this development process. The compound, however, does not affect already existing T-cells, called memory cells, that protect the body from pathogens they have already encountered.
Dr. Kerkvliet concluded that the findings have potential for treating other autoimmune diseases such as colitis, psoriasis, and multiple sclerosis, as well as for the suppression of the immune response required during organ-transplant surgery.
