Study Fuels Progress Toward Predicting An Individual’s Response to MS Therapy

Why do some people respond to MS disease-modifying therapies and others do not? This is the basic question underlying a newly published study that, with further research, could lead to tools to predict who would do best on which therapy and usher in the beginning of personalized medicine for people with MS. The study, funded in part by the National MS Society, is by a collaboration led by Lawrence Steinman, MD (Stanford University) and Chander Raman, PhD (University of Alabama at Birmingham). It was published online on March 28, 2010 in Nature Medicine.

Background: Multiple sclerosis involves immune attacks that target areas of the brain and spinal cord and cause a variety of neurological symptoms. There are seven FDA-approved disease-modifying therapies for people with MS that can reduce the immune attacks and reduce disease activity. Four of these therapies are interferons.

For reasons that are not clear, a significant proportion of individuals with MS do not “respond to,” or benefit from, interferon therapy, but it can take many months or even years to figure that out. Since earlier treatment has been linked to better outcomes, having a way to predict whether a person’s MS would respond to interferon or other therapy could save months or even years of guesswork and potentially improve outcomes.

This Study: In a series of lab investigations, the collaborators tested the idea that response to interferons might depend on which types of immune messengers, called cytokines, were leading the immune attacks typical of MS. They transferred two different types of disease-causing immune T cells into mice, and both were able to produce the MS-like disease EAE. (The two types of T cells are called T helper 1 cells and T helper 17 cells, and each type causes a different pattern of cytokines to become activated.)

Then they tested whether there was any difference in the response of the mice to interferon. They found that interferon reduced EAE symptoms in mice whose disease had been induced by T helper 1 cells, but it worsened disease that had been induced by T helper 17 cells. They also identified which immune messengers were influencing the different responses.

To further explore this phenomenon in human MS, the team examined the profiles of immune messengers apparent in serum samples taken from 26 people with MS before and after they had received interferon therapy, without knowing in advance who had responded to therapy. They found that they could differentiate between those who did not respond to interferon and those who did, based on patterns of cytokines. Those who did not respond had high levels of a cytokine associated with T helper 17 cells (interleukin-17F), and those who did respond had very low levels of this cytokine.

Larger clinical studies will be needed to confirm and expand on these findings and to identify additional potential predictors of therapeutic response not just for interferons but for other MS therapies as well. Nevertheless, this work represents progress toward a future of personalized medicine for people with MS, where doctors would be able to use simple tests to predict optimal treatment regimens for individual patients.

Support for this study included grants from the National Institutes of Health and the National MS Society, especially a postdoctoral fellowship to first author Robert Axtell, PhD, and a Collaborative MS Research Center award to Dr. Steinman, without which, he stated, “this study would never have happened.”

Article taken from www.nmss.org