Title :

A ferroptosis-based panel of prognostic biomarkers for amyotrophic lateral sclerosis

Author(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]

Journal title :

Scientific Reports

Abbreviated title :

Sci Rep

Volume number :

9

Pages :

2918

Publisher :

Nature Publishing Group

Publication date :

2019-02-27

ISSN :

2045-2322

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Submission date :

2019-11-27T14:29:53Z
2021-05-21T13:21:00Z
2022-11-18T15:56:21Z