ArticleAnnals of neurology2026
Skeletal Muscle Biomarkers of Amyotrophic Lateral Sclerosis: A Large-Scale, Multi-Cohort Proteomic Study.
Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Origin and Application of Cardiomyocyte-Derived Small Extracellular Vesicles: A Systematic Review.International journal of medical sciences · 2026Pooled it
- Evaluation of a serum protein signature as monitoring biomarker for Duchenne muscular dystrophy in a long-term clinical trial with corticosteroids.Skeletal muscle · 2026Trial
- Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis.European journal of neurology · 2026Article
- Plasma cardiac troponin T complements neurofilament light chain by reflecting disease phase and phenotypic variation in amyotrophic lateral sclerosis.Journal of neurology · 2026Article
- Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- The Target ALS Global Natural History Study: Cross-platform proteomics to accelerate biofluid biomarker and drug target discovery in amyotrophic lateral sclerosis.medRxiv : the preprint server for health sciences · 2026Article
- Distinct Prescription Patterns Emerge Years Before ALS Diagnosis: A Nationwide Registry-Based Study.Annals of neurology · 2026Article
- A deep joint-learning proteomics model for diagnosis of six conditions associated with dementia.Nature medicine · 2026Article
- Evaluation of a serum protein signature as monitoring biomarker for Duchenne Muscular Dystrophy in a long-term clinical trial with corticosteroids.medRxiv : the preprint server for health sciences · 2026Article
- Beyond neurofilaments: a multidimensional blood signature for amyotrophic lateral sclerosis.Brain communications · 2026Article
- IsomiR Utility in Amyotrophic Lateral Sclerosis Prognostication.medRxiv : the preprint server for health sciences · 2025Article
- Epigenetic profiles of tissue informative CpGs inform ALS disease status and progression.Genome medicine · 2025Article
- Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.Research square · 2025Article
- Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
- Update of
Authors and funding
17 authors.
Funding
Abstract
objectiveBiomarkers with clear contexts of use are important tools for amyotrophic lateral sclerosis (ALS) therapy development. Understanding their longitudinal trajectory in the untreated state is key to their use as potential markers of pharmacodynamic response. To this end, we undertook a large-scale proteomic study in well-phenotyped cohorts to identify biomarker candidates of ALS disease state and disease progression.
methodsClinical phenotypic data and biofluid samples, collected from patients with ALS and healthy controls through multiple longitudinal natural history studies, were used to identify biomarker candidates. Slow off-rate modified aptamer (SOMAmer)-based relatively quantitative measurement of ~7,000 proteins was performed in plasma and cerebrospinal fluid (CSF), with immunoassay validation of candidates of interest.
resultsWe identified 329 plasma proteins significantly differentially regulated between ALS and controls (adjusted p-value <0.05), with 25 showing >40% relative abundance. PDLIM3, TNNT2, and MYL11 had the greatest log-fold elevation, whereas ANTXR2 and ART3 had the greatest log-fold reduction. A similar set of plasma proteins was found to increase (eg, PDLIM3, TNNT2, and MYL11) or decrease (eg, ANTXR2, ART3, and MSTN) with disease progression. CSF proteins with the greatest log-fold elevation included NEFL, NEFH, CHIT1, CA3, MYL11, and GPNMB. These results were confirmed in an independent replication cohort. Moreover, tissue-specific signature enrichment suggests a significant contribution of muscle as a source of these biomarkers. Plasma KCNIP3 was elevated by ~60% in those on riluzole. Immunoassays provided orthogonal validation of plasma TNNT2 and CSF GPNMB.
interpretationWe identified an array of novel biomarkers with the potential to serve as response biomarkers to aid therapy development, as well as to shed light on the underlying biology of disease. ANN NEUROL 2026;99:393-407.
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.