University of Virginia’s Medical School Discovery Puts Forth Efforts To Prevent and Treat MS

Researchers led by the University of Virginia’s Dr. Mariano Garcia-Blanco have identified a series of processes in cells that suppress the risk of developing multiple sclerosis, which could lead to better prevention and treatment therapies.

At the head of the cell processes, the scientists found a gene that acts as a master controller for many other genes important in our susceptibility to MS and the proper functioning of our immune systems.


“It 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,” said Garcia-Blanco, who chairs the Department of Microbiology, Immunology and Cancer Biology, adding that the new understanding could help lead to better, more targeted treatments.

“While 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,” he said.

Multiple sclerosis is a potentially disabling autoimmune disorder in which the immune system begins to attack the sheath-like coverings that protect nerves. The damage interrupts the nerves’ ability to transmit communications through the body. This leads to symptoms such as muscle weakness and stiffness, spasms, fatigue, numbness and difficulty moving. The disease is estimated to affect nearly a million Americans and almost 3 million people worldwide.

The new work from Garcia-Blanco and his collaborators sheds important light on how our immune systems are calibrated to prevent MS. It also identifies several key places where things might go wrong.

For example, the researchers conclude that the master gene they identified, DDX39B, is an “important guardian of immune tolerance.” This means that it helps keeps the body’s immune response working at appropriate levels so that the immune system doesn’t begin to attack the body’s own cells. That’s what happens in MS and other autoimmune diseases.

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.

The new insights 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.

Chloe Nagasawa, a graduate student with Garcia-Blanco and second author of the new scientific paper outlining the findings, said the DDX39B gene could be activated using small-molecule agonists in cases of autoimmune diseases.

“Multiple sclerosis takes a massive toll on patients and society, affecting disproportionately young women, and to date there is no cure,” Nagasawa said. “We believe that basic understanding of molecular mechanisms underpinning immune tolerance will open paths to truly targeted therapy.”

The researchers have published their findings in the scientific journal eLife. The team consisted of Minato Hirano, Gaddiel Galarza-Muñoz, Chloe Nagasawa, Geraldine Schott, Liuyang Wang, Alejandro L. Antonia, Vaibhav Jain, Xiaoying Yu, Steven G. Widen, Farren B.S. Briggs, Simon G. Gregory, Dennis C. Ko, W. Samuel Fagg, Shelton S. Bradrick and Garcia-Blanco.