ReviewAnnals of neurology2024
Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.
Review in Annals of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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
25 citing papers in PubMed, 33 citations in OpenAlex.
- Beyond Biomarkers: Reclaiming the Central Role of Clinical Neurophysiology in Neuromuscular Disorders.Brain sciences · 2026Review
- Toward actionable biomarkers in psychiatry: a collaborative roadmap for precision clinical trials. An ACNP position paper.NPP - digital psychiatry and neuroscience · 2026Article
- Human biomarker navigator.iMeta · 2026Review
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Impact of Plasma p-tau181 on Cognition, Motor Phenotypes, and Disease Course in ALS.Annals of clinical and translational neurology · 2026Article
- Anchoring ALS Prognosis: Neurofilament Light Chain Outperforms Inflammatory, Metabolic, and CNS Barrier Biomarkers in the METABALS Cohort.Molecular neurobiology · 2026Article
- 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
- Big Tau: Structure, Evolutionary Divergence, and Emerging Roles in Cytoskeletal Dynamics and Tauopathies.Cells · 2026Review
- Modulation of the miR-485-3p/PGC-1α Pathway by ASO-Loaded Nanoparticles Attenuates ALS Pathogenesis.International journal of molecular sciences · 2026Article
- Nonlinear combinatorial analysis of blood transcriptomes identifies PRKAR1A as a regulator of TDP-43 pathophysiology in amyotrophic lateral sclerosis.Biology methods & protocols · 2026Article
- Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.Annals of neurology · 2025Article
- Review
- Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment.Journal of inherited metabolic disease · 2025Review
- Kv3 channel agonist ameliorates the phenotype of a mouse model of amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Blood Biomarkers Reflecting Brain Pathology-From Common Grounds to Rare Frontiers.Journal of inherited metabolic disease · 2025Review
- Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies.Life (Basel, Switzerland) · 2025Review
- Rethinking phase 2 trials in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2025Article
- The role of Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in MS and AQP4-NMOSD: Advancing clinical applications.eNeurologicalSci · 2025Review
- The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
objectiveTo explore whether the utility of neurofilament light chain (NfL), as a biomarker to aid amyotrophic lateral sclerosis (ALS) therapy development, would be enhanced by obtaining formal qualification from the US Food and Drug Administration for a defined context-of-use.
methodsConsensus discussion among academic, industry, and patient advocacy group representatives.
resultsA wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts-of-use, the US Food and Drug Administration has provided accelerated approval for an SOD1-lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.
interpretationThe increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility-as a prognostic, response, risk/susceptibility, and/or safety biomarker-is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer-reviewed data-absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts-of-use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211-216.
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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.