MS Biomarkers Could Lead to a New Era of Personalized Care

Living with multiple sclerosis (MS) can be a journey of uncertainty, marked by unpredictable neurological symptoms and the gradual progression of disability. Although a wide array of treatments exists, the challenge remains in selecting the most effective and personalized approach for each person, especially as higher-intensity treatments carry a greater risk of immune suppression.

Despite the increase in MS prevalence, gaps in accurate prevalence estimates continue to exist across various regions, underscoring the need for more comprehensive global data to better understand and manage the disease's impact. | Image credit: Julien Tromeur - stock.adobe.com

A new review paper published in Neurotherapeutics summarized the growing body of evidence supporting the use of soluble biomarkers as a key tool for creating a more individualized care model.¹

The Need for a New Approach

More than 2.8 million people worldwide are estimated to be living with MS.² The global prevalence of this chronic immune-mediated disease has risen since 2013, with a notable mean age of diagnosis at 32 years. Women are disproportionately affected, being twice as likely as men to live with the condition. Despite the increase in prevalence, gaps in accurate prevalence estimates continue to exist across various regions, underscoring the need for more comprehensive global data to better understand and manage the disease's impact.

The pathophysiology of MS is not fully understood, and its clinical course can vary dramatically among individuals. Historically, diagnosis has relied on a person's clinical symptoms and MRI findings, which show lesions in the central nervous system over time. While incremental improvements to these diagnostic criteria have led to earlier identification of people who could benefit from treatment, a more nuanced approach is needed. The review highlighted that biomarkers are a pivotal tool for assisting in this goal, as they can provide critical insights into disease activity and help clinicians detect subclinical changes that could prevent further neurological damage.

The review paper, authored by researchers from the University of Ottawa and Montreal Neurological Institute, focused on the potential of 2 early and promising biomarkers: neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). These proteins can be reliably measured from a simple blood sample and provide insights into nerve damage and astrocyte turnover, respectively.

The authors summarized several key findings from the literature:

• Predicting disease course: in an analysis of 704 patients from the Brigham and Women's Hospital Longitudinal MS Cohort (CLIMB), adding baseline sNfL and sGFAP levels improved a predictive model's ability to forecast secondary progressive MS at the 10-year mark. The model's accuracy increased from an area under the curve of 0.73 to 0.77, a statistically significant improvement.
• Early detection: a large US cohort study found that sNfL levels in people who went on to develop MS began to increase as early as 6 years before they experienced their first clinical symptoms.
• Correlation with disease activity: the review noted that higher baseline sNfL levels were associated with greater T2 lesion volume and brain atrophy after 10 years. Similarly, higher sGFAP levels were more likely to be associated with progressive disease.
• Monitoring treatment response: the paper cited several clinical trials that demonstrated effective medications led to a reduction in sNfL levels. Conversely, a failure to suppress sNfL could indicate ongoing tissue injury and a suboptimal response to treatment. The authors also pointed out that for people who discontinued treatment, those who showed a greater increase in their sNfL or sGFAP levels were more likely to experience clinical and MRI worsening.

Patient Demographics and Limitations

The review synthesized data from various cohorts, including a large US study that examined the link between Epstein-Barr virus infection and MS risk. Although the findings were promising, the review also acknowledged several limitations. For example, sNfL, while a quick and cost-effective test, does not have widespread access or a fast enough turnaround time to be useful for immediate intervention. The paper also noted that sNfL may lack the specificity to differentiate between MS, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein–associated disease, particularly when measured near an acute attack.

Overall, the authors concluded that these biomarkers have the potential to transform MS care. "By integrating biomarker analysis into routine clinical assessments, health care providers may move toward a more nuanced and individualized care model, better equipped to meet the challenges posed by these multifaceted diseases." The ability to assess a person’s disease activity and risk of progression through a simple blood test marks a significant step toward precision medicine in neuroimmunology.

References

1. Bose G, Thebault SDX, Fadda G, Brooks JA, Feedman MS. Role of soluble biomarkers in treating multiple sclerosis and neuroinflammatory conditions. Neurotherapeutics. 2025;22(4):e00588. doi:10.1016/j.neurot.2025.e00588

2. B Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816-1821. doi:10.1177/1352458520970841