ArticleBrain : a journal of neurology2023
Neurofilament light chain in drug development for amyotrophic lateral sclerosis: a critical appraisal.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis.Journal of neurology · 2026Pooled it
- Biomarkers in ALS trials: from discovery to clinical utility.Frontiers in neuroscience · 2025Pooled it
- Trial
- Serum Neurofilament Light Chain and GFAP in Amyotrophic Lateral Sclerosis on a Commercial ECLIA Platform.Muscle & nerve · 2026Article
- Article
- Plasma Proteomic Signatures Predict Incident Amyotrophic Lateral Sclerosis: A Prospective Study Stratified by C9orf72 Expansion.Journal of cachexia, sarcopenia and muscle · 2026Article
- Beyond Biomarkers: Reclaiming the Central Role of Clinical Neurophysiology in Neuromuscular Disorders.Brain sciences · 2026Review
- Effects of Dietary Supplementation with Conjugated Linoleic Acid on Redox Marker Profiles and Neuroaxonal Degeneration in Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2026Article
- Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS.Nature medicine · 2026Article
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Metabolic and Fluid Biomarkers Support Microglia Activation in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.Translational neurodegeneration · 2026Review
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Integration of Serum Neurofilament Light Chain and Cortical Dysfunction Improves Diagnostic Accuracy in ALS.Annals of clinical and translational neurology · 2026Article
- Small RNA sequencing identifies serum tDR-1:34-Gly-GCC tiRNA levels as a biomarker for survival in amyotrophic lateral sclerosis.iScience · 2026Article
- Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-TreatedInternational journal of molecular sciences · 2026Article
- Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial.Scientific reports · 2026Article
- Electrochemical Detection of Neuronal Injury in Cell Culture Samples: A Cost-Effective Biosensor for Neurofilament Light Sensing.Biosensors · 2026Article
- Knowledge mapping of biomarkers in amyotrophic lateral sclerosis: a comprehensive bibliometric and visual analysis.Neurodegenerative disease management · 2026Review
- Longitudinal Dynamics of Plasma Neurofilament Light Chain in Hereditary Spastic Paraplegia Type 11 (HSP-SPG11) and Type 15 (HSP-ZFYVE26).Movement disorders : official journal of the Movement Disorder Society · 2026Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Interest in amyotrophic lateral sclerosis (ALS) biomarkers has grown exponentially over the course of the last 25 years, with great hope that they might serve as tools to facilitate the development of meaningful therapies for this otherwise inexorably progressive and invariably fatal disease. Effective use of biomarkers, however, requires an understanding of what it means for them to be 'fit-for-purpose' as well as an appreciation of the nuances of the clinical context(s) in which they will be applied. Neurofilament light chain (NfL) has emerged as a leading candidate with enormous potential to aid ALS therapy development; it is, however, also profoundly misunderstood. Within the conceptual framework of the BEST (Biomarkers, EndpointS, and other Tools) Resource, developed by the National Institutes of Health and the Food and Drug Administration in the USA, we consider the evidence supporting the use of NfL for a variety of purposes in different clinical contexts. We conclude that: (i) it may serve as a susceptibility/risk biomarker in populations at elevated risk for ALS; (ii) it has value as a prognostic biomarker when measured early in the course of established disease, empowering stratification or dynamic randomization to amplify the signal-to-noise ratio of promising therapeutics; and (iii) there is sufficient evidence to support the use of a reduction in NfL in response to an experimental therapeutic as a pharmacodynamic biomarker that may aid in phase 2 trial go/no-go decisions. Moreover, the basis for expecting that a reduction in NfL is a reasonably likely surrogate end-point (i.e. reasonably likely to predict clinical benefit-which may be more than simply survival) is nuanced, and depends on when in the course of disease the experimental therapeutic is administered.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.