Multiple sclerosis (MS), a complex immune-mediated disease of the central nervous system, is notoriously complex—not only in how it affects individuals but also in how differently people respond to treatments. One such treatment, interferon-beta (IFN-β), has long been a frontline therapy for managing relapsing forms of MS. However, up to half of all patients do not respond effectively to it. Why this happens remains a major question in MS research.

Now, a newly published study in the International Journal of Molecular Sciences offers an intriguing clue: perhaps your genes—specifically variations in two immune-related genes, CCR5 and CTLA-4—could help predict your likelihood of benefiting from IFN-β therapy.

Let’s explore what this research uncovered and what it means for the future of personalized MS treatment. The Genetic Puzzle of MS Treatment
This study, conducted by a collaborative team of scientists from Croatia and Slovenia, set out to understand whether certain gene polymorphisms—essentially small genetic variations—might influence how well MS patients respond to IFN-β.

The focus was on two key genes:

CCR5, a chemokine receptor gene involved in immune cell migration to inflammation sites.

CTLA-4, a gene crucial in regulating immune response and maintaining immune system "checkpoints."

Both genes have been studied in relation to MS in the past, but their roles in treatment response remain unclear.

The Study: What They Did
The researchers analyzed blood samples from 295 MS patients (230 women and 65 men) in Croatia and Slovenia. These patients had been treated with IFN-β for at least two years and were classified as either:

Responders (173 patients), meaning no relapses and no disease progression. Non-responders (122 patients), meaning at least one relapse and worsening disability. They then looked for specific variants in the CCR5 gene (specifically the ∆32 deletion) and in CTLA-4 (+49 A/G polymorphism), using standard PCR-based genotyping techniques.

Why Is This Important?
CTLA-4 +49 AA Genotype in Women Matters
The study found a statistically significant association between the CTLA-4 +49 AA genotype and positive response to IFN-β therapy in female patients. Women with this genotype were more likely to respond well to treatment than those without it.

CCR5 ∆32 Variant Not Linked to Treatment Response Although previously suggested to influence MS progression, the CCR5 ∆32 variant did not appear to affect IFN-β treatment response in this cohort.

Combined Genetic Effect
Interestingly, women who carried both the CTLA-4 +49 AA genotype and the wild-type CCR5 (wtwt) had an even stronger likelihood of responding positively to treatment.

No Predictive Value in Men or Clinical Features
In contrast, none of the genetic variants studied showed predictive value in male patients, and traditional clinical factors like age at disease onset or baseline disability also failed to predict treatment response.

What Does This Mean?
This research suggests that genetic testing could play a role in personalizing MS treatment, especially for women. Knowing whether a female patient carries the CTLA-4 +49 AA genotype could help neurologists determine if IFN-β is a suitable first-line therapy or if alternative treatments should be considered.

It also underscores the importance of considering sex-based biological differences in MS research and treatment. Women and men don't just experience MS differently—they may also respond differently to the same treatments due to genetic factors.

Why Is This Important?
MS is a lifelong disease with no cure, and the earlier a treatment plan can be tailored to a patient’s biology, the better the long-term outcomes. With IFN-β still widely used due to its safety and accessibility, identifying who is likely to benefit from it could save patients valuable time and spare them ineffective therapy.

Moreover, this study contributes to the growing field of pharmacogenetics—the science of how our genes influence our responses to drugs. It's a field that promises to transform one-size-fits-all medicine into precision medicine, where treatments are designed around the individual, not the average patient.

Caveats and Next Steps
While the findings are compelling, the study has limitations:

The sample size, especially among male patients, was relatively small.

The observation period was limited to two years.

The study only examined two genetic polymorphisms out of many potentially involved in treatment response.

The researchers themselves call for larger, more diverse studies to validate these results and expand our understanding of genetic influences on MS therapy.

Final Thoughts
If you're a woman with MS considering or currently on IFN-β therapy, your genetic profile might one day help guide that decision. We're not quite there yet in clinical practice—but research like this is laying the groundwork.

As we continue to unravel the genetics of MS, the dream of personalized medicine comes closer to reality—offering hope for more effective, tailored treatments that change lives.

Disclaimer: This blog post is based on the information provided in the cited scientific article. It aims to provide an accessible summary of the research findings and should not be considered as definitive medical advice. For any health concerns, please consult with a qualified healthcare professional.

Reference:
Nekić, J., Stanković Matić, I., Rački, V., et al. (2024). CCR5 ∆32 and CTLA-4 +49 A/G Gene Polymorphisms and Interferon-β Treatment Response in Croatian and Slovenian Multiple Sclerosis Patients. International Journal of Molecular Sciences, 25(7412).