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Review
. 2021 Mar 25:15:654942.
doi: 10.3389/fnins.2021.654942. eCollection 2021.

Serum Neurofilament Light Chain Measurement in MS: Hurdles to Clinical Translation

Simon Thebault  1 , Ronald A Booth  2 , Carolina A Rush  1 , Heather MacLean  1 , Mark S Freedman  1
Affiliations
Review

Serum Neurofilament Light Chain Measurement in MS: Hurdles to Clinical Translation

Simon Thebault et al. Front Neurosci. .

Abstract

Measurement of serum neurofilament light chain concentration (sNfL) promises to become a convenient, cost effective and meaningful adjunct for multiple sclerosis (MS) prognostication as well as monitoring disease activity in response to treatment. Despite the remarkable progress and an ever-increasing literature supporting the potential role of sNfL in MS over the last 5 years, a number of hurdles remain before this test can be integrated into routine clinical practice. In this review we highlight these hurdles, broadly classified by concerns relating to clinical validity and analytical validity. After setting out an aspirational roadmap as to how many of these issues can be overcome, we conclude by sharing our vision of the current and future role of sNfL assays in MS clinical practice.

Keywords: biomarker; blood; multiple sclerosis; neurofilament light; translation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Barriers to the clinical translation of sNfL in 2021.
FIGURE 2
FIGURE 2
Proposed algorithm for NfL monitoring in MS. *Clinical or MRI disease activity: New relapses, EDSS worsening, New/enlarging MRI lesion. **sNfL 95% age-dependent upper reference interval calculated on SiMOA HD1 instrument using Quanterix NF-lightTM (Hviid et al., 2020). ***The increase in sNfL from baseline that best denotes impending disease activity that should prompt further action is still to be determined. Preliminary data from 58 patients with MS followed every 3 months over 1 year suggests that a doubling of sNfL from baseline is associated with a 2.2 × relative risk of relapse (Thebault, Unpublished observation).
FIGURE 3
FIGURE 3
Aspirational predictions of sNfL in the next 5–10 years.
See this image and copyright information in PMC

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