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

Caroline Moreau 1, 2 Véronique Danel Jean Devedjian Guillaume Grolez 3 Kelly Timmerman 3 Charlotte Laloux 3 Maud Petrault 3 Flore Gouel 3 Aurélie Jonneaux 3 Mary Dutheil 3, 4 Cédrick Lachaud 3 Renaud Lopes 3 Gregory Kuchcinski 3 Florent Auger 3 Maeva Kyheng 5 Alain Duhamel 5 Thierry Perez 6 Pierre Pradat 7 Hélène Blasco 8, 9 Charlotte Veyrat-Durebex 10 Philippe Corcia 11, 9 Patrick Oeckl Markus Otto 12 Luc Dupuis 13 Guillaume Garçon 14 Luc Defebvre 15 Z. Loav Cabantchik James Duce 16, 17 Regis Bordet 3 David Devos 3
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 Sod1 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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Contributeur : Okina Université d'Angers <>
Soumis le : lundi 25 mai 2020 - 03:36:44
Dernière modification le : lundi 14 juin 2021 - 13:58:07

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Caroline Moreau, Véronique Danel, Jean Devedjian, Guillaume Grolez, Kelly Timmerman, et al.. Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis?. Antioxidants & Redox Signaling, 2018, 29, pp.742-748. ⟨10.1089/ars.2017.7493⟩. ⟨hal-02616908⟩



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