Scientists from the
Florida campus of The Scripps Research Institute (TSRI) have successfully
tested a potent synthetic compound that prevents type 1 diabetes in animal
models of the disease.
“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.
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