A breakthrough study has revealed two biomarkers that can predict whether disability will worsen in patients newly diagnosed with multiple sclerosis (MS), in findings that could lead to more personalized and effective treatments for the condition.
The research revealed the importance of a protein linked with nerve damage called serum neurofilament light chain (sNfL) and another protein called serum glial fibrillary acidic protein (sGFAP), which is derived from astrocytes and released in the bloodstream upon injury or inflammation to the central nervous system (CNS).
Different levels of these two proteins, and the relationship between the two, predicted future disability in MS patients and which drug strategies they might most benefit from.
“The identification of sNfL and sGFAP as predictive biomarkers allows us to tailor treatment strategies for MS patients more effectively,” said Enric Monreal, PhD, from Ramón y Cajal University Hospital in Madrid, whose team presented their research at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Copenhagen this week.
He added: “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.”
The prognosis was positive for patients with low levels of both biomarkers, and they could successfully be treated with injectable or oral disease-modifying treatments (DMTs).
But MS patients with high levels of sNfL, which indicated acute inflammation within the CNS, often did not respond well to these standard treatments and did much better with high-efficacy DMTs such as natalizumab, alemtuzumab, ocrelizumab, rituximab, and ofatumumab.
The situation was further complicated for MS patients who had high sGFAP, indicative of more localized inflammation, but low sNfL levels as they did not respond well to current DMTs, indicating the need for new therapeutic approaches.
“These distinct pathways in MS have significant therapeutic implications, as current DMTs primarily target the peripheral adaptive immune system without affecting CNS immunity,” Monreal explained.
“Therefore, identifying patients with higher levels of peripheral inflammation is crucial for preventing disability and improving patient outcomes.”
Disability in patients with MS arises through two primary means: either incomplete recovery following a relapse, known as relapse-associated worsening (RAW); or the gradual progression of disability outside any relapse activity, known as progression independent of relapse activity (PIRA).
The study of blood samples collected within 12 months of MS onset from 725 patients at 13 hospitals in Spain and Italy revealed that elevated sNfL at the onset of MS were associated with a 45% increased risk of RAW and a 43% increased risk of PIRA.
However, patients with high sGFAP but low sNfL levels showed an 86% increased risk of PIRA and did not respond to current treatments. sGFAP values only predicted PIRA in patients with low sNfL levels.
“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,” said Monreal.
“This approach aims to prevent disability while avoiding unnecessary treatment-related risks for those at lower risk.”
