Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis?© Caroline Moreau et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
| Autor: | Charlotte Veyrat-Durebex, Renaud Lopes, Maeva Kyheng, Guillaume Grolez, Guillaume Garçon, Florent Auger, Luc Defebvre, Thierry Perez, Flore Gouel, Veronique Danel, Kelly Timmerman, James A. Duce, Jean-Christophe Devedjian, Mary Dutheil, Pierre-François Pradat, Philippe Corcia, Luc Dupuis, Grégory Kuchcinski, Caroline Moreau, Ioav Cabantchik, Markus Otto, Maud Pétrault, David Devos, Régis Bordet, Alain Duhamel, Charlotte Laloux, Aurélie Jonneaux, Patrick Oeckl, Cédrick Lachaud, Hélène Blasco |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Anemia Clinical Biochemistry Pharmacology medicine.disease_cause Placebo Biochemistry Neuroprotection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid medicine Chelation Amyotrophic lateral sclerosis Molecular Biology General Environmental Science 2. Zero hunger business.industry Cell Biology medicine.disease 3. Good health 030104 developmental biology chemistry General Earth and Planetary Sciences Deferiprone business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Antioxidants & Redox Signaling. 29:742-748 |
| ISSN: | 1557-7716 1523-0864 |
| Popis: | Iron accumulation has been observed in mouse models and in both sporadic and familial forms of amyotrophic lateral sclerosis (ALS). Iron chelation could reduce iron accumulation and the related excess of oxidative stress in the motor pathways. However, classical iron chelation would induce systemic iron depletion. We assess the safety and efficacy of conservative iron chelation (i.e., chelation with low risk of iron depletion) in a murine preclinical model and pilot clinical trial. In Sod1G86R mice, deferiprone increased the mean life span compared with placebo. The safety was good, without anemia after 12 months of deferiprone in the 23 ALS patients enrolled in the clinical trial. The decreases in the ALS Functional Rating Scale and the body mass index were significantly smaller for the first 3 months of deferiprone treatment (30 mg/kg/day) than for the first treatment-free period. Iron levels in the cervical spinal cord, medulla oblongata, and motor cortex (according to magnetic resonance imaging), as well as cerebrospinal fluid levels of oxidative stress and neurofilament light chains were lower after deferiprone treatment. Our observation leads to the hypothesis that moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality of neuroprotection for ALS. Antioxid. Redox Signal. 29, 742-748. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|