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Expert Panel Outlines Promise of a Biomarker to Predict Disease Course and Speed Treatments for Progressive MS

September 7, 2020

  • There is an unmet need for treatments that can stop and prevent disease worsening for those in progressive stages of multiple sclerosis.
  • One impediment is the lack of a quick way to detect whether a therapy is working, since progression can occur slowly. The search has been on for biomarkers that can predict disease activity and detect response to therapy.
  • To advance this search, the International Progressive MS Alliance, a global initiative that includes leadership from the National MS Society, convened a panel of experts to evaluate the potential of “neurofilament light” (NfL) as a fluid biomarker in MS and progressive MS in particular, and to outline research needed to advance the field.
  • The panel has now published a paper that summarizes what is known about NfL as a potential biomarker, and makes recommendations for further research to refine its potential to predict disease course and detect response to therapy in progressive MS.
Background: Amidst a growing list of disease-modifying therapies for relapsing forms of multiple sclerosis, there is an unmet need for treatments that can stop and prevent disease worsening for those in progressive stages of the disease.
Clinical trials involving people with relapsing MS often rely on counting relapses or MRI-detected lesions to detect disease activity. Progression is less easily measured, and usually happens over longer periods of time. This makes it hard to detect quickly whether a therapy is slowing or stopping progression in early phase 2 proof of concept clinical trials. This is a serious roadblock for developing therapies for progressive MS.
Having objective indicators that detect progression, measure treatment impact, and predict an individual’s course and response to therapy would speed the development of new therapies and improve care for progressive MS.
Expert Panel Convened: To consider the current state of research on fluid biomarkers in MS in general and progressive MS specifically, the International Progressive MS Alliance convened a panel of experts, including people affected by MS, scientists, and MS clinicians, with a view to mobilizing the MS community toward filling key gaps in knowledge and understanding. Under the leadership of Raju Kapoor, FRCP  (then at University College London) and Robert J. Fox, MD (Cleveland Clinic) the panel’s first published paper summarizes the state of knowledge about neurofilament light (NfL), and provides recommendations for next steps to advance NfL as a potential biomarker for MS.
Neurofilament Light: Neurofilaments are important proteins that function to maintain nerve cell structure necessary for proper electrical impulse conduction along axons (nerve wires). NfL is a fragment that is part of the debris that enters the spinal fluid and blood when axons are damaged by MS and other causes. Recent technological advances have enabled the detection of NfL in the blood (serum and plasma), and not just in spinal fluid obtained by spinal tap, which makes it more convenient and practical as a potential biomarker.
Studies of NfL in serum, plasma and spinal fluid have been underway to better define how this biomarker may be employed to help detect and predict disease activity, progression, and response to treatments, not only in MS but in other neurologic disorders. NfL is also detected in healthy individuals, and its concentrations increase with age, so it is important to understand what is normal and what is not.
Recent clinical trials in MS have incorporated periodic monitoring of NfL levels as a possible indicator of treatment effect. The paper and accompanying tables outline how NfL levels behave before and after treatment in the course of clinical trials in both relapsing and progressive forms of MS. Results vary, but generally suggest that on a group level (rather than in individuals), NfL levels can predict relapse rates, brain tissue loss, disability progression, and are indicators of treatment response.
Recommendations: The authors outline additional research needed to establish the value of serum NfL as a biomarker in progressive MS and to have it recognized by drug regulators as a measure of treatment response in clinical trials. These include:
  • Standard protocols should be established for how fluid samples for NfL detection are collected, handled, stored and analyzed, so that findings may be compared across multiple studies.
  • Establishing normal NfL values across a broad age range of individuals with and without known medical issues, and potential confounding factors such as smoking, is a critical next step. Having these “normative” values not only increase the value of NfL as a biomarker in clinical trials, but will also facilitate its use for guiding treatment decisions in individuals, which is not yet understood.
  • Additional studies of prior clinical trial data are needed to further understand how predictive serum NfL levels are of future disease activity and progression, how they correspond with MRI findings, and how they are influenced by inflammation and various therapies.
Studies Underway: The authors highlight several studies that are already underway that will help establish normative values of NfL, the impact of lifestyle, age and other demographic factors, and help define its predictive value, not just in MS but other disorders. Additional molecules are also under investigation as potential fluid biomarkers.
The International Progressive Multiple Sclerosis Alliance and its partners will continue to advance these initiatives to support its goal of speeding the development of therapies for progressive stages of MS.
The paper, “Serum Neurofilament Light as a Biomarker in Progressive Multiple Sclerosis,” was published in the September 8, 2020 online issue of Neurology,® the medical journal of the American Academy of Neurology, by authors Raju Kapoor, FRCP  (University College London), Robert J Fox, MD (Mellen Center for Multiple Sclerosis, Cleveland Clinic), and their international collaborators. Anyone can read the paper without a subscription.
Listen to a RealTalkMS podcast interview with some of the authors
Learn more about the International Progressive MS Alliance

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.


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