A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00121482" target="_blank" >RIV/00216224:14110/19:00121482 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41598-019-39739-5.pdf" target="_blank" >https://www.nature.com/articles/s41598-019-39739-5.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-019-39739-5" target="_blank" >10.1038/s41598-019-39739-5</a>
Alternative languages
Result language
angličtina
Original language name
A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30210 - Clinical neurology
Result continuities
Project
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Continuities
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Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Scientific Reports
ISSN
2045-2322
e-ISSN
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Volume of the periodical
9
Issue of the periodical within the volume
FEB 2019
Country of publishing house
GB - UNITED KINGDOM
Number of pages
6
Pages from-to
1-6
UT code for WoS article
000459799800067
EID of the result in the Scopus database
2-s2.0-85062279348