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

Caroline Moreau, Véronique Danel, Jean Christophe Devedjian, Guillaume Grolez, Kelly Timmerman, Charlotte Laloux, Maud Petrault, Flore Gouel, Aurélie Jonneaux, Mary Dutheil, Cédrick Lachaud, Renaud Lopes, Grégory Kuchcinski, Florent Auger, Maeva Kyheng, Alain Duhamel, Thierry Pérez, Pierre François Pradat, Hélène Blasco, Charlotte Veyrat-DurebexPhilippe Corcia, Patrick Oeckl, Markus Otto, Luc Dupuis, Guillaume Garçon, Luc Defebvre, Z. Ioav Cabantchik, James Duce, Régis Bordet, David Devos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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.

Original languageEnglish
Pages (from-to)742-748
Number of pages7
JournalAntioxidants and Redox Signaling
Volume29
Issue number8
DOIs
StatePublished - 10 Sep 2018

Bibliographical note

Publisher Copyright:
© Caroline Moreau et al..

Keywords

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

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