Researchers led by Mariano Garcia-Blanco, MD, PhD, chair of the Department of Microbiology, Immunology and Cancer Biology have discovered a key determinant of our risk for multiple sclerosis (MS), advancing efforts to prevent and better treat the disease.<\/p>\n
The group identified a series of processes in our cells that suppresses our risk for developing multiple sclerosis. At the head of these processes, the scientists found, is a gene that acts as a master controller for many other genes important in our susceptibility to MS and in the proper functioning of our immune systems. <\/p>\n
\u201cIt is remarkable that a protein that unwinds RNA is a central player in how we recognize our cells as our own, not to be confused with invading pathogens,\u201d Garcia-Blanco said. He noted that the new understanding could help lead to better, more targeted treatments: \u201cWhile there are effective treatments for multiple sclerosis and other autoimmune diseases, most of these lead to general suppression of the immune system and makes patients susceptible to infections or incapable of responding well to vaccines.\u201d<\/p>\n
The new work from Garcia-Blanco and his collaborators sheds important light on how our immune systems are calibrated to prevent MS and identifies several key places where things might go wrong. For example, the researchers conclude that the master gene they identified, DDX39B, is an \u201cimportant guardian of immune tolerance.\u201d This means that it helps keeps the body\u2019s immune response working at the appropriate levels, so that the immune system doesn\u2019t begin to attack the body\u2019s own cells \u2013 as is the case in MS and other autoimmune diseases.<\/p>\n
This master gene, the researchers found, directs the activity of another gene critical in the production of important immune cells called T regulatory cells (Tregs) previously linked to MS. This second gene, FOXP3, is already known to play a critical role in autoimmune disorders.<\/p>\n
These new insights into how the immune system functions, or should function, help doctors and scientists better understand the underlying causes of multiple sclerosis and give them attractive targets in their efforts to develop new treatments and preventive measures. <\/p>\n
\u201cIn cases of autoimmune diseases, we would want to activate DDX39B with small-molecule agonists, for which there is strong pre-clinical precedent,\u201d said Chloe Nagasawa, a graduate student with Garcia-Blanco and second author of the new scientific paper outlining the findings. \u201cMultiple sclerosis takes a massive toll on patients and society, affecting disproportionately young women, and to date there is no cure. We believe that basic understanding of molecular mechanisms underpinning immune tolerance will open paths to truly targeted therapy.\u201d<\/p>\n