Biomarkers sNfL and sGFAP Predict Disability Worsening in Multiple Sclerosis
Key Insights
A new study identifies serum neurofilament light chain (search) (sNfL) and serum glial fibrillary acidic protein (search) (sGFAP) as key biomarkers for predicting disability worsening in multiple sclerosis (search) (MS).
Elevated sNfL levels at MS onset correlate with increased risk of both relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA).
High sGFAP levels, combined with low sNfL, indicate an increased risk of PIRA and poor response to current disease-modifying treatments (DMTs).
A recent study presented at ECTRIMS 2024 has identified serum neurofilament light chain (search) (sNfL) and serum glial fibrillary acidic protein (search) (sGFAP) as predictive biomarkers for disability worsening in multiple sclerosis (search) (MS). The multi-center observational study, conducted across 13 hospitals in Spain and Italy, analyzed blood samples from 725 MS patients within 12 months of disease onset, potentially paving the way for personalized and effective treatment plans.
Key Findings on Biomarkers and MS Progression
Using the Single Molecule Array (SIMOA) technique, researchers assessed the prognostic value of sNfL and sGFAP levels to predict relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). The study revealed that higher sNfL levels, indicative of acute inflammation within the central nervous system (CNS) in MS, are associated with a 45% increased risk of RAW and a 43% increased risk of PIRA.
Patients with high sNfL levels often did not respond well to standard disease-modifying treatments (DMTs) but showed significant benefits from high-efficacy DMTs (HE-DMTs) such as natalizumab, alemtuzumab, ocrelizumab, rituximab, and ofatumumab. In contrast, patients with high sGFAP levels—an indicator of more localized inflammation driven by microglia in the CNS—and low sNfL levels experienced an 86% increased risk of PIRA and did not respond to current DMTs.
Implications for Personalized Treatment
Dr. Enric Monreal, a researcher in MS at Ramón y Cajal University Hospital (search) and the study's first author, emphasized the importance of these findings for tailoring treatment strategies. "The identification of sNfL and sGFAP as predictive biomarkers allows us to tailor treatment strategies for MS patients more effectively," he stated. Patients with low levels of both biomarkers had a good prognosis and could be treated with injectable or oral DMTs. However, high sNfL levels indicate a need for HE-DMTs to prevent disability worsening, while patients with high sGFAP levels and low sNfL values may require new therapeutic approaches.
The Need for Novel Therapeutic Approaches
Monreal further explained that current DMTs primarily target the peripheral adaptive immune system without affecting CNS immunity. Therefore, identifying patients with higher levels of peripheral inflammation is crucial for preventing disability and improving patient outcomes. The study underscores the critical need for personalized treatment approaches to effectively manage the millions of people affected by MS worldwide, many of whom have chronic disability that significantly impacts their quality of life.
Study Design and Methodology
The study analyzed blood samples from 725 MS patients collected within 12 months of disease onset across 13 hospitals in Spain and Italy. Researchers used the Single Molecule Array (SIMOA) technique to assess the prognostic value of sNfL and sGFAP levels to predict RAW and PIRA. This approach allowed for the accurate measurement of low protein concentrations, providing valuable insights into the progression pathways of MS.
Conclusion
By measuring both sNfL and sGFAP levels at disease onset, clinicians can gain valuable insights into the progression pathways of MS, enabling them to identify the optimal patients for specific DMTs. This approach aims to prevent disability while avoiding unnecessary treatment-related risks for those at lower risk.