A ferroptosis-based panel of prognostic ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
A ferroptosis-based panel of prognostic biomarkers for amyotrophic lateral sclerosis
Auteur(s) :
DEVOS, DAVID [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U1171
moreau, caroline [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U1171
Kyheng, MaÉva [Auteur]
Service de Biostatistiques [CHRU Lille]
Garcon, Guillaume [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Rolland, Anne-Sophie [Auteur]
Blasco, Helene [Auteur]
Gelé, Patrick [Auteur]
Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 [CIC Lille]
Lenglet, Timothee [Auteur]
Veyrat-Durebex, Charlotte [Auteur]
Corcia, Philippe [Auteur]
Dutheil, Mary [Auteur]
Bede, Peter [Auteur]
Jeromin, Andreas [Auteur]
Oeckl, Patrick [Auteur]
Otto, Markus [Auteur]
Meninger, Vincent [Auteur]
Danel-Brunaud, Veronique [Auteur]
Devedjian, Jean-Christophe [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Duce, James A. [Auteur]
Pradat, Pierre-François [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U1171
moreau, caroline [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U1171
Kyheng, MaÉva [Auteur]
Service de Biostatistiques [CHRU Lille]
Garcon, Guillaume [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Rolland, Anne-Sophie [Auteur]
Blasco, Helene [Auteur]
Gelé, Patrick [Auteur]
Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 [CIC Lille]
Lenglet, Timothee [Auteur]
Veyrat-Durebex, Charlotte [Auteur]
Corcia, Philippe [Auteur]
Dutheil, Mary [Auteur]
Bede, Peter [Auteur]
Jeromin, Andreas [Auteur]
Oeckl, Patrick [Auteur]
Otto, Markus [Auteur]
Meninger, Vincent [Auteur]
Danel-Brunaud, Veronique [Auteur]
Devedjian, Jean-Christophe [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Duce, James A. [Auteur]
Pradat, Pierre-François [Auteur]
Titre de la revue :
Scientific Reports
Nom court de la revue :
Sci Rep
Numéro :
9
Pagination :
2918
Éditeur :
Nature Publishing Group
Date de publication :
2019-02-27
ISSN :
2045-2322
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
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 ...
Lire la suite >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 functional decline. The identified four biomarkers are all closely associated with 'ferroptosis', a recently discovered form of programmed cell death with promising therapeutic targets. The predictive potential of these pathophysiology-based indicators may offer superior patient stratification for future trials, individualised patient care and resource allocation.Lire moins >
Lire la suite >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 functional decline. The identified four biomarkers are all closely associated with 'ferroptosis', a recently discovered form of programmed cell death with promising therapeutic targets. The predictive potential of these pathophysiology-based indicators may offer superior patient stratification for future trials, individualised patient care and resource allocation.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille
Date de dépôt :
2019-11-27T14:29:53Z
2021-05-21T13:21:00Z
2022-11-18T15:56:21Z
2021-05-21T13:21:00Z
2022-11-18T15:56:21Z
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- Devos et al.pdf
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