Identifying MS Gene Mutations Could Make Personalized Treatment Possible

Personalized medicine, often applied to treat cancer, may be possible for patients with multiple sclerosis as well. Certain patients respond differently to certain multiple sclerosis medications, such as interferon-β (IFNβ), and researchers at San Raffaele Scientific Institute in Milan may have an answer as to why. The team, led by Federica Esposito, MD, PhD, found that multiple sclerosis patients with a specific mutation in the gene SLC9A9 have more frequent relapses despite treatment with IFNβ.

“A proportion of multiple sclerosis patients experience disease activity despite treatment,” wrote Dr. Esposito, explaining the motivation behind the study. “The early identification of the most effective drug is critical to impact long-term outcome and to move toward a personalized approach.”

To achieve this goal, the research team looked for associations between multiple sclerosis patient gene expression and response to treatment with IFNβ. The researchers’ findings, published in Annals of Neurology and entitled, “A Pharmacogenetic study Implicates SLC9a9 in Multiple Sclerosis Disease Activity,” demonstrated that a genetic mutation in the gene SLC9a9, namely the rs9828519^G variant, can be used to predict how multiple sclerosis patients will respond to treatment.

“Exploring the function of this gene, we see that SLC9A9 mRNA expression is diminished in multiple sclerosis subjects who are more likely to have relapses,” noted Dr. Esposito. When the research team used patient-derived T cells to study the effects of SLC9A9 gene expression on IFN, they saw an increase in the pro-inflammatory molecule IFNγ.

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The new information in this study may be able to screen multiple sclerosis patients for efficacious disease therapies. For example, if a patient carries a mutation in SLC9A9 that prevents its transcription into mRNA, that patient may not be well suited for IFNβ and may be a candidate for a different treatment option.

The idea is similar to that of MSPrecise, best described by an article published in Gene, “MSPrecise: A Molecular Diagnostic Test for Multiple Sclerosis Using Next Generation Sequencing.” This screen also finds mutations in DNA, specifically in cerebrospinal fluid-derived B cells that express a VH4 gene. Clinicians have shown it accurately identifies 84% of patients who develop relapsing-remitting multiple sclerosis (RRMS). If used together, a clinician may be able to determine if an individual has RRMS via MSPrecise, then determine if IFNβ is a suitable treatment by testing for SLC9A9 mutations.

At present, currently approved multiple sclerosis therapies are developed to treat a wide range of patients and are tested on diverse patient populations in order to determine if they are relatively effective in treating the disease in across a broad clinical population. However, as the human DNA is decoded and gene mutations are better understood, the more possible it becomes to tailor future MS therapies to maximize therapeutic value for each individual patient.