J 2019

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

DEVOS, D., C. MOREAU, M. KYHENG, G. GARCON, A. S. O. ROLLAND et. al.

Basic information

Original name

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

Authors

DEVOS, D., C. MOREAU, M. KYHENG, G. GARCON, A. S. O. ROLLAND, H. BLASCO, P. GELE, T. T. LENGLET, C. VEYRAT-DUREBEX, P. CORCIA, M. DUTHEIL, P. BEDE, A. JEROMIN, P. OECKL, M. OTTO, V. MENINGER, V. DANEL-BRUNAUD, J. C. DEVEDJIAN, J. A. DUCE and P. F. PRADAT

Edition

Nature Scientific Reports, London, NATURE RESEARCH, 2019, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.998

RIV identification code

RIV/00216224:14110/19:00121482

Organization unit

Faculty of Medicine

UT WoS

000459799800067

Keywords in English

Amyotrophic Lateral Sclerosis; prognostic biomarkers

Tags

International impact, Reviewed
Změněno: 28/4/2021 09:29, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

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