A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis

Scientific Reports
David DevosPierre François Pradat

Abstract

Accurate patient stratification into prognostic categories and targeting Amyotrophic Lateral Sclerosis (ALS)-associated pathways may pave the way for promising trials. We evaluated blood-based prognostic indicators using an array of pathological markers. Plasma samples were collected as part of a large, phase III clinical trial (Mitotarget/TRO19622) at months 1, 6, 12 and 18. The ALSFRS-r score was used as a proxy of disease progression to assess the predictive value of candidate biological indicators. First, established clinical predictors were evaluated in all 512 patients. Subsequently, pathologic markers, such as proxies of neuronal integrity (Neurofilament light chain and phosphorylated heavy chain), DNA oxidation (8-oxo-2'-desoxyguanosine), lipid peroxidation (4-hydroxy-2-nonenal, isoprostane), inflammation (interleukin-6) and iron status (ferritin, hepcidin, transferrin) were assessed in a subset of 109 patients that represented the whole cohort. Markers of neuronal integrity, DNA and lipid oxidation, as well as iron status at baseline are accurate predictors of disability at 18-month follow-up. The composite scores of these markers in association with established clinical predictors enable the accurate forecasting of fu...Continue Reading

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Citations

Oct 28, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Karla AcevedoAshley I Bush
May 7, 2020·Frontiers in Neurology·Pamela A McCombeRobert D Henderson
Jun 23, 2020·Expert Review of Neurotherapeutics·Pamela A McCombeRobert D Henderson
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Jan 11, 2020·Frontiers in Neuroscience·Kyle J TrageserGiulio Maria Pasinetti
Jan 11, 2020·Frontiers in Neurology·Peter Bede, Pierre-Francois Pradat
Aug 19, 2020·Antioxidants & Redox Signaling·Behrouz HassanniaTom Vanden Berghe
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Feb 27, 2021·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Stacey Li Hi ShingPeter Bede
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Jan 8, 2022·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Eoin FineganPeter Bede

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Clinical Trials Mentioned

NCT00868166

Software Mentioned

SAS

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