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Antioxid Redox Signal. 2018 Sep 10;29(8):742-748. doi: 10.1089/ars.2017.7493. Epub 2018 Feb 8.

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

Author information

1
1 Department of Neurology, ALS Center, Lille University, INSERM UMRS_1171, University Hospital Center , LICEND COEN Center, Lille, France .
2
2 Department of Medical Pharmacology, Lille University, INSERM UMRS_1171, University Hospital Center , LICEND COEN Center, Lille, France .
3
3 Department of Neuroradiology, Lille University, INSERM UMRS_1171, University Hospital Center , LICEND COEN Center, Lille, France .
4
4 Department of Preclinical Radiology, Lille University , INSERM UMRS_1171, LICEND COEN Center, Lille, France .
5
5 Department of Biostatistic, University of Lille , CHU Lille, EA 2694-Santé Publique: épidémiologie et qualité des soins, Lille, France .
6
6 Department of Pneumology, Lille University, University Hospital Center , Lille, France .
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7 Laboratoire d'Imagerie Biomédicale, Sorbonne Universités, UPMC University Paris 06 , CNRS, Inserm, Paris, France .
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8 Département de Neurologie, AP-HP, Hôpital Pitié-Salpêtrière , Paris, France .
9
9 Laboratoire de Biochimie, Université François Rabelais , INSERM U930, CHRU, Tours, France .
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10 Department of Neurology, Center for Biomedical Research, Ulm University Hospital , Ulm, Germany .
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11 INSERM UMR-S1118, Faculté de Médecine de , Strasbourg, France .
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12 EA4483 Department of Toxicology, CHU of Lille University , Lille, France .
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13 Della Pergola Chair, Alexander Silberman Institute of Life Sciences, Hebrew University , Jerusalem, Israel .
14
14 Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge , Cambridge Biomedical Campus, Cambridge, United Kingdom .
15
15 The Florey Institute of Neuroscience and Mental Health, University of Melbourne , Parkville, Victoria, Australia .

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.

KEYWORDS:

amyotrophic lateral sclerosis; conservative iron chelator; neuroprotection; oxidative stress; treatment

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