Scientists have discovered a way to prevent the development of multiple sclerosis in mice. Using a drug that blocks the production of a certain type of immune cell linked to inflammation and autoimmunity, the researchers successfully protected against the onset of MS in an animal model of the disease.
In the immune system, two kinds of T cells strike a delicate balance--T helper cells (Th17) activate the immune system, protecting against infections and cancers, while regulatory T cells (Tregs) suppress the system, keeping it in check. A disparity between these cell types, where there are too many Th17 and not enough Tregs, can lead to a hyperactive immune system, resulting in inflammation, tissue damage, and autoimmune disease.
In the current study, published in the Journal of Experimental Medicine, the researchers discovered that an important regulatory protein, sirtuin 1 (SIRT1), is involved in the production of Th17 cells. By blocking this protein, the scientists can protect against the onset of autoimmunity. SIRT1 also has a negative impact on Treg maturation and maintenance, so inhibiting its expression simultaneously enhances the production of Tregs and suppresses the creation of Th17.
To test this effect on disease, the researchers used a mouse model of MS and treated the animals with a drug that inhibits SIRT1. Typically, MS-model mice experience severe motor problems, eventually leading to paralysis, but when they were given the drug the mice behaved perfectly normally. Moreover, the treated animals showed no signs of inflammation or cell damage in their spines, classic markers for MS.
In contrast with the current research, SIRT1 is typically thought of as having anti-inflammatory properties, and compounds that increase SIRT1--like resveratrol--have been proposed as a way to delay aging. However, first author Hyungwook Lim, PhD, a postdoctoral fellow at Gladstone, says the new research suggests that the protein's effects are more complicated.
"We are very excited about these findings," says Eric Verdin, MD, a senior investigator at Gladstone Institute and co-senior author on the study. "In light of the significant effect the treatment had on inflammation, the implications of these results will likely extend beyond multiple sclerosis to other types of autoimmune disorders. We are particularly interested in testing this in type I diabetes given the similar pathways involved, and we are already seeing very promising results in preliminary experiments."
Other Gladstone investigators on the study include Jae Kyu Ryu, Mingjian Fei, Intelly Lee, Kotaro Shirakawa, Herbert Kasler, Hye-Sook Kwon, Katerina Akassoglou, and Melanie Ott, who was a co-senior author on the paper. Scientists from the University of California San Francisco, Scripps Research Institute, Buck Institute for Research on Aging, National Institute of Infectious Diseases Japan, German Cancer Research Center, New York University School of Medicine, and Howard Hughes Medical Institute also took part in the research. Funding was provided by the Kurtzig and Mulholland families, the National Center for Research Resources, and the National Center for Biotechnology Information.