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 language | English |
|---|---|
| Pages (from-to) | 742-748 |
| Number of pages | 7 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 29 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published (in print/issue) - 10 Sept 2018 |
Funding
C.M. has received grants from the France Parkinson charity. She has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia, including Aguettant, AbbVie, Medtronic, and Novartis. V.D., J.C.D., G.G., K.T., M.P., C.L., F.G., A.J., M.D., C.L., R.L., C.V.-D., G.K., F.A., A.D., M.K., H.B., T.P., P.J.-T., L.D., G.G., P.O., R.B., and J.D. have nothing to declare. P.C. served on the advisory board and received honoraria from Roche for consultancy and grants from the ARSLA charity. P.F.P. has received grants from the ARSLA charity, the Association Franc¸aise contre les Myopathies-Téléthon (AFM-Téléthon), the Institut pour la Recherche sur la Moelle épinière et l’Encéphale (IRME), the T.L. Foundation, and the Target ALS Foundation. L.D. served on the Scientific Advisory Board for Novartis and Aguettant, and has received honoraria from pharmaceutical companies for consultancy and lectures. M.O. received grants from the European Union (FAIRPARK-II), German Ministry of Science and Technology (KNDD-FTLDc), T.L. Foundation, ALS Foundation, Foundation of the state Baden-Wuerttemberg, and the German Science Foundation. He has served as advisor for Axon, Biogen, and given lectures for Lilly, Fujirebio, and Teva. D.D. has received PHRC grants from the French Ministry of Health and research funding from the ARSLA charity, the France Parkinson charity, and the Credit Agricole Foundation. He has led two investigator-driven pilot studies involving deferiprone (FAIRPARK-I and SAFE-FAIR ALS-I), provided free of charge by ApoPharma. He has served on advisory boards, served as a consultant, and given lectures for pharmaceutical companies such as Orkyn, Aguettant, AbbVie, Medtronic, Novartis, Teva, UCB, Lundbeck, and ApoPharma.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- amyotrophic lateral sclerosis
- conservative iron chelator
- neuroprotection
- oxidative stress
- treatment
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