Moreau, C, Danel, V, Devedjian, JC et al. (27 more authors) (2018) Could conservative iron chelation lead to neuroprotection in amyotrophic lateral sclerosis? Antioxidants and Redox Signaling, 29 (8). pp. 742-748. ISSN 1523-0864
Abstract
Iron accumulation has been observed in mouse models and both sporadic and familial forms of Amyotrophic lateral sclerosis. 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 as 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 (BMI) 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 MRI), 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 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. |
Keywords: | amyotrophic lateral sclerosis; conservative iron chelator; oxidative stress; neuroprotection; treatment |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Feb 2018 16:02 |
Last Modified: | 29 Dec 2018 01:38 |
Status: | Published |
Publisher: | Mary Ann Liebert, Inc. |
Identification Number: | 10.1089/ars.2017.7493 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:126871 |