Biomarkers for predicting multiple sclerosis progression identified
Researchers have identified biomarkers that can predict disease progression in multiple sclerosis, which could lead to the development of more personalized treatment strategies.
Multiple sclerosis (MS) is a chronic autoimmune disease of the brain and spinal cord that affects myelin, the protective sheath around nerve fibers and oligodendrocytes, the cells responsible for producing myelin. With the condition affecting millions of people worldwide, there remains an unmet diagnostic need to assess progression in individuals with MS. Now, in what could be a significant step forward, findings from a multi-center study presented at ECTRIMS 2024 (Copenhagen, Denmark;18–20 September 2024) has identified two biomarkers, serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP), that can predict disability worsening outcomes in MS patients. The findings pave the way for personalized treatment strategies for patients.
sNfL is a cytoskeletal protein that can enter the serum following neuronal damage. Recent studies have established the protein as a biomarker for neuronal damage; however, its use as a biomarker for assessing progression is yet to be established [1]. sGFAP is an astrocyte cytoskeleton protein that has been previously proposed as a biomarker for identifying disease progression and for predicting future progression in MS patients [1].
For people with MS, disability can be acquired through two main mechanisms: relapse-associated worsening (RAW), associated with incomplete recovery following a relapse, and progression independent of relapse activity (PIRA), the gradual worsening of disability independent of a relapse. The team set out to determine how levels of sNfL and sGFAP correlated with disease progression, and whether they could be biomarkers for predicting RAW and PIRA in individuals with MS.
In the study, the team analyzed a total of 725 blood samples collected from people with MS across 13 hospitals in Spain and Italy within 12 months of disease onset. Single-molecule array (SIMOA) technology was used to assess the prognostic value of sNfL and sGFAP levels. A key factor in choosing this approach was the technology’s ability to digitalize immunoassays, allowing low protein concentrations to be measured more effectively when compared to traditional immunoassays.
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Findings revealed that elevated levels of sNfL were associated with a 45% increased risk of RAW and a 43% increased risk of PIRA. The researchers found that patients with elevated sNfL did not respond well to standard disease-modifying therapies (DMTs) but showed improvements when treated with high-efficacy DMTs, including immunotherapies such as natalizumab and ocrelizumab.
In patients with elevated levels of sGFAP and reduced levels of sNfL, there was an 86% increased risk of PIRA, with patients not responding to current DMTs, emphasizing the need for new treatment approaches.
With sGFAP known to be associated with progression, an observation that took the researchers by surprise was the inability to predict progression with sGFAP values when sNfL levels were elevated. The team found that sGFAP values were only predictive of PIRA in patients with low levels of sNfL.
The researchers also found that patients with low levels of both biomarkers were likely to positively respond to standard DMTs.
Discussing the significance of the findings within the context of precision medicine, Eric Monreal (Hospital Universitario Ramón y Cajal, Madrid, Spain), first author of the study stated, “By measuring both sNfL and sGFAP levels at disease onset, we gain valuable insights into the progression pathways of MS, enabling clinicians 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.”
The identification of the biomarkers marks a positive step towards improving treatment outcomes for people with MS through precision medicine. “The results of this study underscore 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,” commented Monreal.
