Serum neurofilament light as a biomarker in progressive multiple sclerosis

Abstract

There is an unmet need in multiple sclerosis (MS) therapy for treatments to stop progressive disability. The development of treatments may be accelerated if novel biomarkers are developed to overcome the limitations of traditional imaging outcomes revealed in early phase trials. In January 2019, the International Progressive Multiple Sclerosis Alliance convened a standing expert panel to consider potential tissue fluid biomarkers in MS in general and in progressive MS specifically. The panel focused their attention on neurofilament light chain (NfL) in serum or plasma, examining data from both relapsing and progressive MS. Here, we report the initial conclusions of the panel and its recommendations for further research. Serum NfL (sNfL) is a plausible marker of neurodegeneration that can be measured accurately, sensitively, and reproducibly, but standard procedures for sample processing and analysis should be established. Findings from relapsing and progressive cohorts concur and indicate that sNfL concentrations correlate with imaging and disability measures, predict the future course of the disease, and can predict response to treatment. Importantly, disease activity from active inflammation (i.e. new T2 and gadolinium-enhancing lesions) is a large contributor to sNfL, so teasing apart disease activity from the disease progression that drives insidious disability progression in progressive MS will be challenging. More data is required on the effects of age and comorbidities, as well as the relative contributions of inflammatory activity and other disease processes. The International Progressive Multiple Sclerosis Alliance is well positioned to advance these initiatives by connecting and supporting relevant stakeholders in progressive MS.

Blood Neurofilament Light Chain: The Neurologist’s Troponin?

“…In primary progressive disease, reductions were seen following fingolimod [ 80 ] and ocrelizumab [ 78 ]. Given the lack of useful biomarkers otherwise for progressive types of MS, NfL is increasingly seen as an important secondary endpoint in phase 2 and 3 studies of treatments [ 81 ].…”

Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high‐dose pharmaceutical‐grade biotin (MD1003)

“…NfL is a marker of axonal loss and correlated significantly with inflammatory markers for MS activity, markers of neurodegeneration such as brain volume loss and therapeutic response (Kuhle et al., 2019). In our study, the course of the mean level of pNfL showed an increase at M3 and a slow decrease until M12, whereas the natural history of pNfL in the placebo groups of PMS shows stabilization or a regular increase over time (Kapoor et al., 2020). In addition, the course of the mean BV and CSCV was stable throughout the year.…”

Should We Use Clinical Tools to Identify Disease Progression?

“…Beyond imaging, other structural biomarkers are under development and validation in progressive MS. Neurofilament light chain (Nfl) is a novel marker that can be detected in serum or in cerebrospinal fluid with a good correlation between both measures ( 40 , 53 , 54 ). This non-specific biomarker serves as evidence of neuronal destruction and has a good correlation with MRI measures and possible with the risk of developing SPMS ( 25 , 55 , 56 ). However, technical methods for the analysis and Nfl concentrations in healthy subjects and at early phases of the disease should be addressed ( 56 ).…”

“…This non-specific biomarker serves as evidence of neuronal destruction and has a good correlation with MRI measures and possible with the risk of developing SPMS ( 25 , 55 , 56 ). However, technical methods for the analysis and Nfl concentrations in healthy subjects and at early phases of the disease should be addressed ( 56 ). Future research should focus on the use of this biomarker for the monitoring of treatment response and disease progression.…”