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@article{1763937,
author = {Devos, D. and Moreau, C. and Kyheng, M. and Garcon, G. and Rolland, A. S. O. and Blasco, H. and Gele, P. and Lenglet, T. T. and VeyratandDurebex, C. and Corcia, P. and Dutheil, M. and Bede, P. and Jeromin, A. and Oeckl, P. and Otto, M. and Meninger, V. and DanelandBrunaud, V. and Devedjian, J. C. and Duce, J. A. and Pradat, P. F.},
article_location = {London},
article_number = {FEB 2019},
doi = {http://dx.doi.org/10.1038/s41598-019-39739-5},
keywords = {Amyotrophic Lateral Sclerosis; prognostic biomarkers},
language = {eng},
issn = {2045-2322},
journal = {Nature Scientific Reports},
title = {A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis},
url = {https://www.nature.com/articles/s41598-019-39739-5.pdf},
volume = {9},
year = {2019}
}
TY - JOUR
ID - 1763937
AU - Devos, D. - Moreau, C. - Kyheng, M. - Garcon, G. - Rolland, A. S. O. - Blasco, H. - Gele, P. - Lenglet, T. T. - Veyrat-Durebex, C. - Corcia, P. - Dutheil, M. - Bede, P. - Jeromin, A. - Oeckl, P. - Otto, M. - Meninger, V. - Danel-Brunaud, V. - Devedjian, J. C. - Duce, J. A. - Pradat, P. F.
PY - 2019
TI - A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
JF - Nature Scientific Reports
VL - 9
IS - FEB 2019
SP - 1-6
EP - 1-6
PB - NATURE RESEARCH
SN - 20452322
KW - Amyotrophic Lateral Sclerosis
KW - prognostic biomarkers
UR - https://www.nature.com/articles/s41598-019-39739-5.pdf
N2 - 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.
ER -
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. A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis. \textit{Nature Scientific Reports}. London: NATURE RESEARCH, 2019, vol.~9, FEB 2019, p.~1-6. ISSN~2045-2322. Available from: https://dx.doi.org/10.1038/s41598-019-39739-5.
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