Researchers have found differences in genetic material between people who respond to interferon beta treatment and those who don’t, in a study of 287 people with relapsing-remitting MS+. These results, if confirmed by larger studies and explored further, are an important step toward using genetic information to predict who will respond to specific therapies for MS, laying early groundwork that may one day guide treatment decisions for patients and their doctors. Esther Byun, MD and Jorge Oksenberg, PhD (University of California, San Francisco) led an international collaboration, funded by the National Institutes of Health, that presents its results in the Archives of Neurology (Early Release Article, posted January 14, 2008).
Three interferon beta medications have been approved by the U.S. Food and Drug Administration for treating relapsing forms of MS**. However, a significant number of people who are treated with interferon beta continue to experience relapses and worsening disability despite treatment. If we could predict who would respond to interferons, it would help guide treatment choices to more effectively counter immune attacks early in the course of the disease, a critical period when treatment choices may help determine a person’s future condition.
Study Details: Dr. Oksenberg and colleagues used a cutting-edge approach to determine if there were genetic differences between people who respond to interferon beta and those who don’t. They chose to study people with MS from four centers in Southern Europe, to minimize differences in the groups’ genetic backgrounds. People were enrolled who had relapsing-remitting MS and who experienced at least two relapses before beginning treatment with interferon beta. They were then followed for two years while on treatment. Those who had no relapses and no increase in disability (measured by the EDSS, a scale used to measure MS disease activity) over those two years were considered responders. Those who experienced at least two relapses during follow up and an EDSS increase of one point or more were considered nonresponders. About half of the patients studied were responders, and half were nonresponders.
The team screened the “genome” all the genetic information of these participants -- using gene chip technology capable of analyzing 100,000 genetic variations at once. Looking both at pooled material and at individuals’ genes, they looked for variations in genetic material that would appear more or less often in responders versus nonresponders. After completing the first stage of analysis, they increased the statistical power of the study by adding genetic data from 81 more patients.
Results: The first screen identified 35 variations (SNPs, or single nucleotide polymorphisms, the most common type of variation in genetic material) that differed between responders and nonresponders. The second screen narrowed this down to 18 of these SNPs.
The genetic variations that differed among responders and nonresponders provide some interesting information about how interferons may work. For example, two SNPs appear in genes involved in nerve signaling. SNPs were also found to differ between responders and nonresponders in the gene for “glypican-5,” a protein implicated in nerve growth and repair. Other SNPs existed in the genes for “extracellular matrix proteins,” which may impact how effectively cells involved in the immune attack in MS can enter the central nervous system.
This study represents an important but early step toward finding a way to predict who will do best on which therapy for MS. Larger studies are needed to confirm the findings, and more research should help determine how these particular genetic variations affect the clinical experiences of people with MS.
-- Research and Clinical Programs Department
+Relapsing-remitting MS a course of MS in which clearly defined flare-ups are followed by partial or complete recovery periods but in which there is no progression between relapses.
**Relapsing forms This includes relapsing-remitting MS in addition to progressive forms of MS that are associated with relapses.