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.Základní údaje
Originální název
A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
Autoři
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 a P. F. PRADAT
Vydání
Nature Scientific Reports, London, NATURE RESEARCH, 2019, 2045-2322
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30210 Clinical neurology
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 3.998
Kód RIV
RIV/00216224:14110/19:00121482
Organizační jednotka
Lékařská fakulta
UT WoS
000459799800067
Klíčová slova anglicky
Amyotrophic Lateral Sclerosis; prognostic biomarkers
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 28. 4. 2021 09:29, Mgr. Tereza Miškechová
Anotace
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.
Návaznosti
90090, velká výzkumná infrastruktura |
|