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    Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis?

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    Author
    Moreau, C; Danel, V; Devedjian, JC; Grolez, G; Timmerman, K; Laloux, C; Petrault, M; Gouel, F; Jonneaux, A; Dutheil, M; ...
    Date
    2018-02-08
    Source Title
    Antioxidants and Redox Signaling
    Publisher
    MARY ANN LIEBERT, INC
    University of Melbourne Author/s
    Duce, James
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
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    Document Type
    Journal Article
    Citations
    Moreau, C., Danel, V., Devedjian, J. C., Grolez, G., Timmerman, K., Laloux, C., Petrault, M., Gouel, F., Jonneaux, A., Dutheil, M., Lachaud, C., Lopes, R., Kuchcinski, G., Auger, F., Kyheng, M., Duhamel, A., Perez, T., Pradat, P. F., Blasco, H. ,... Devos, D. (2018). Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis?. ANTIOXIDANTS & REDOX SIGNALING, 29 (8), pp.742-748. https://doi.org/10.1089/ars.2017.7493.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256016
    DOI
    10.1089/ars.2017.7493
    Abstract
    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.

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