Your Genes May Know If Interferon Beta Will Work for Your MS

Multiple sclerosis (MS) remains one of the most complex and variable neurological disorders. While interferon beta (IFNβ) has long served as a cornerstone in the treatment of relapsing-remitting MS, its effectiveness varies widely between patients. What if a simple genetic test could help predict who will benefit from this treatment—and who won't?

A genome-wide association study (GWAS), presented in poster P05.141 at the 2013 American Academy of Neurology (AAN) Annual Meeting by Federica Esposito and colleagues, offers promising evidence that a single nucleotide polymorphism (SNP) in the SLC9A9 gene may help do just that.

Understanding the Problem: One Treatment, Many Responses
Patients with MS often face a trial-and-error approach when it comes to selecting their disease-modifying therapy. Interferon beta, although widely prescribed, fails to produce meaningful improvements in a significant subset of patients. The lack of early markers for treatment response can result in prolonged exposure to ineffective therapies, risking disease progression and disability.

The Study: A Genome-Wide Approach to Personalization
Esposito and her team began by analyzing genetic differences between responders and non-responders to IFNβ in an Italian cohort of relapsing-remitting MS patients. Using a GWAS approach, they scanned the entire genome for variants that correlated with treatment response.

One variant stood out: rs9828519G, located in an intronic (non-coding) region of the SLC9A9 gene.

Key Findings:
rs9828519G was significantly associated with a poor response to IFNβ (p = 4.43 × 10⁻⁸).

Each additional G allele increased the likelihood of non-response, pointing to an additive genetic effect.

The association held true in three independent replication cohorts from the U.S., Italy, and France.

A meta-analysis confirmed the robustness of the finding (p = 0.0007).

Notably, this SNP did not affect response to glatiramer acetate, suggesting treatment-specific genetic effects.

What Is SLC9A9, and Why Does It Matter?
SLC9A9 encodes a sodium-hydrogen exchanger, a protein involved in maintaining the pH balance within cells and regulating intracellular trafficking. Although not previously highlighted as a player in MS, this gene may be functionally significant in immune cell activation or neuroinflammation.

Interestingly, the implicated SNP resides in an intronic region, which doesn't code for protein directly but may affect RNA splicing—the process by which different protein isoforms are generated. Preliminary functional analyses by the authors suggest that rs9828519 may influence the expression of alternative splice variants of SLC9A9, possibly altering its function in immune cells.

Clinical Implications: Toward Personalized MS Therapy
If validated in larger, diverse cohorts, rs9828519 could become a valuable biomarker to guide initial treatment decisions for MS patients. By genotyping this single variant, clinicians might be able to:

Predict which patients are less likely to benefit from IFNβ.

Avoid months (or years) of ineffective treatment.

More quickly shift non-responders to alternative therapies, such as glatiramer acetate or newer biologics.

This study exemplifies how precision medicine—tailoring treatment based on genetic information—is becoming a practical reality in neurology.

What’s Next?
The researchers rightly point out that their findings, while compelling, require further validation. Larger studies are needed to refine predictive models, explore gene-gene and gene-environment interactions, and investigate how SLC9A9 expression actually influences IFNβ's mechanism of action.

Still, the work of Esposito and colleagues lays the foundation for a future in which MS therapy is no longer one-size-fits-all but based on individual molecular profiles.

Takeaway
A variant in the SLC9A9 gene (rs9828519G) is associated with reduced response to interferon beta in MS patients, offering a potential genetic marker for personalized treatment strategies.

As the landscape of MS therapy grows more complex, tools like this could prove invaluable in ensuring the right patient gets the right treatment—right from the start.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Esposito F. et al., “An SLC9A9 Variant Influences Treatment Response in Interferon beta Treated Multiple Sclerosis Patients,” AAN Poster P05.141, Neurology February 12, 2013, 80(7 Supplement).