Multiple sclerosis (MS) can present differently in people. It can range from clinically isolated incidents (CIS) and relapsing-remitting MS (RRMS) to a more disabling, progressive form of MS.
People who originally receive a diagnosis of RRMS may transition into progressive MS, taking 10 to 15 years to do so.
Many people don’t progress at all.
Little is known about what drives the development of progressive MS, but inflammatory factors may contribute to this path.
A recent study has discovered two closely related molecules that may explain why some people develop progressive MS.
The research comes from Yale University, Oregon Health Science University (OHSU), and University of California, San Francisco.
It was supported financially by the National Multiple Sclerosis Society (NMSS).
A molecular problem
The molecules involved are known as a macrophage migration inhibitory factor (MIF) and its related protein, D-dopachrome tautomerase (D-DT).
MIF and D-DT cause inflammation. They work by binding to the CD74 receptor, which triggers inflammatory reactions throughout the body.
These molecules are called cytokines. They can wreck havoc on the central nervous system if overproduced.
In the study, researchers discovered that there were elevated MIF and D-DT levels in men with the progressive disease compared to men with RRMS.
It’s the first time a correlation between MIF and D-DT cytokine levels in the blood of male subjects with a severe form of MS was revealed.
“To prevent progressive disease would be a big help,” Arthur Vandenbark, a professor of neurology and molecular microbiology and immunology at the OHSU School of Medicine and the study’s co-senior author, told Healthline. “While a cure is what everyone wants, this points the way for targeted therapy in an at-risk population.”
He explained that the focus on understanding disease modifiers and what makes MS worse is what’s important.
A genetic marker discovered
The study also revealed for the first time a genetic marker that connects these molecules with males who have progressive MS.
This suggests that a simple genetic test could be used to identify people with MS who are at risk of developing a more severe form of the disease.
The study was based on a hypothesis that the genetic markers that enhance production of MIF would predispose males to make more of this cytokine than others in the population.
Some genetic markers go with high expression of MIF and D-DT, so researchers looked at males with high levels of MIF and D-DT to see if they had these genetic markers.
The researchers concluded they did, allowing for ways to “target and potentially stop progression,” said Vandenbark.
“It is not an absolute test for who will progress,” Bruce Bebo, executive vice president of research at NMSS, told Healthline, “There are plenty of men with this genetic change that do not have progressive disease, and many with progressive disease that do not have this marker.”
While there’s an increased risk for a more progressive disease, it’s not an absolute.
What lies ahead
The next step is to identify drugs in development or approved for therapy that could block this overproduction of MIF.
Studies to treat people with MS over time to prevent the transition from RRMS to progressive MS would require some years of follow up, explained Vandenbark, due to the time needed to observe changes in the study population.
“One day, we might be able to use this knowledge to help predict who is at a higher risk for developing progressive MS,” Bebo said. “But more work still needs to be done before this can be a reality.”
Dr. Jaime Imitola, director of the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at The Ohio State University, told Heathline that this was a “very timely and important study, but [I’m] cautious to extrapolate too much from the data.”
While the data was statistically significant, it needs to be repeated, and with a larger population group.
MIF was one of the first cytokines discovered and has been studied as an inflammatory factor in the past. But it wasn’t known until now how it might contribute to a progression of the illness.
Perhaps the most important role of MIF has to do with progressive MS rather than RRMS.
“This study is changing people’s thoughts as to what MIF can do and the role MIF might have in progressive MS,” explained Bebo.