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Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis

Magen, I; Yacovzada, NS; Yanowski, E; Coenen-Stass, A; Grosskreutz, J; Lu, C-H; Greensmith, L; ... Hornstein, E; + view all (2021) Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis. Nature Neuroscience , 24 (11) pp. 1534-1541. 10.1038/s41593-021-00936-z. Green open access

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Abstract

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA–protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA–protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.

Type: Article
Title: Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41593-021-00936-z
Publisher version: https://doi.org/10.1038/s41593-021-00936-z
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10139140
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