Gladstone Institutes scientists have discovered a successful new treatment that could potentially be used in multiple sclerosis (MS). The treatment involves suppressing a protein that traditionally is associated with overall good health. The study, SIRT1 Deacetylates RORγt and Enhances Th17 Cell Generation, appeared April 27, 2015 in the Journal of Experimental Medicine and has shed new light on conventional thinking about immune response and MS.
MS is an autoimmune disorder in which the immune system launches an attack on the body’s own myelin. Myelin insulates nerve cells, helping them to communicate. When an autoimmune response damages myelin, poor nerve cell (neuron) communication results, causing problems with movement, sensation, pain and loss of vision.
Gladstone scientists found that by blocking a specific protein, they could help prevent autoimmune responses in the nervous system. Led by Hyung W. Lim, the researchers discovered that the protein sirtuin 1 (SIRT1) helps to produce Th17 cells, a type of immune cell that assists in creating an autoimmune response. Blocking SIRT1 produced beneficial effects in a mouse model of MS, since mice with experimental MS developed severe problems with movement and eventual paralysis, which were resolved upon SIRT1 blockade.
“We are very excited about these findings,” says Eric Verdin, MD, a senior investigator at Gladstone 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.”
The research is a bit controversial since it was previously believed that the SIRT1 protein prevents — not enhances — immune responses. Hyungwook Lim, PhD, a postdoctoral fellow, explained new ideas about SIRT1 suggested by the study, “The conventional theory has been that you should activate SIRT1 to improve health and longevity, but we show that this can have negative consequences,” says Dr. Lim. “Instead, we think the role of SIRT1 very much depends on the type of tissue being targeted. For instance, in immune cells, instead of being anti-inflammatory SIRT1 appears to have a pro-inflammatory role, which makes it a prime target to treat autoimmune disorders.”
SIRT1 activation could be beneficial in some cases, but not in others, such as in autoimmune diseases like MS. Further studies of drugs that inhibit SIRT1 may be a promising avenue for the development of MS treatments.