دورية أكاديمية
A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis.
| العنوان: | A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis. |
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| المؤلفون: | Devos, David, Moreau, Caroline, Kyheng, Maeva, Garçon, Guillaume, Rolland, Anne Sophie, Blasco, Hélène, Gelé, Patrick, Timothée Lenglet, T, Veyrat-Durebex, C, Corcia, Philippe, Dutheil, Mary, Bede, Peter, Jeromin, Andreas, Oeckl, Patrick, Otto, Markus, Meininger, Vincent, Danel-Brunaud, Véronique, Devedjian, Jean-Christophe, Duce, James A, Pradat, Pierre François |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1038/s41598-019-39739-5 Sci Rep |
| سنة النشر: | 2019 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | 8-Hydroxy-2'-Deoxyguanosine, Adult, Aldehydes, Amyotrophic Lateral Sclerosis, Biomarkers, Disease Progression, Female, Ferritins, Ferroptosis, Follow-Up Studies, Humans, Iron, Isoprostanes, Lipid Peroxidation, Male, Middle Aged, Neurofilament Proteins, Neurons, Predictive Value of Tests, Prognosis |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/291383Test |
| DOI: | 10.17863/CAM.38555 |
| الإتاحة: | https://doi.org/10.17863/CAM.38555Test https://www.repository.cam.ac.uk/handle/1810/291383Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.F65F0A33 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.38555 |
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