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Bioavailable Trace Metals in Neurological Diseases

  • Neurologic Manifestations of Systemic Disease (N Scolding and C Rice, Section Editors)
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Opinion statement

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron.

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Acknowledgments

JD is supported by the European Research Council and Australian National Health & Medical Research Council (NHMRC) (#1061587). DD was supported by the French Ministry of Health for funding PHRC grants, the Association of patients ARSLA, the French Parkinson’s Disease Association, DN2M and the European Union (Program Horizon 2020 PHC13-2014/2015 N°633190). Apopharma has provided DFP and placebo formulations for the clinical trials reported in the manuscript.

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Authors and Affiliations

  1. French National Reference Centre for Wilson’s Disease, University Hospital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Aurélia Poujois MD, PhD, Pascal Chaine MD & France Woimant MD

  2. Department of Neurology, University Hospital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Aurélia Poujois MD, PhD, Pascal Chaine MD & France Woimant MD

  3. INSERM U1171, CHU Lille, Lille University, Lille, France

    Jean-Christophe Devedjian PhD, Caroline Moreau MD, PhD & David Devos MD, PhD

  4. Department of Medical Pharmacology, CHU Lille, Lille University, Lille, France

    Jean-Christophe Devedjian PhD, Caroline Moreau MD, PhD & David Devos MD, PhD

  5. Department of Movement Disorders and Neurology, CHU Lille, Lille University, Lille, France

    David Devos MD, PhD

  6. School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, UK

    James A. Duce PhD

  7. Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia

    James A. Duce PhD

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  1. Aurélia Poujois MD, PhD
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  2. Jean-Christophe Devedjian PhD
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  3. Caroline Moreau MD, PhD
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  4. David Devos MD, PhD
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  5. Pascal Chaine MD
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  6. France Woimant MD
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  7. James A. Duce PhD
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Correspondence to Aurélia Poujois MD, PhD.

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Conflict of Interest

Aurélia Poujois, Jean-Christophe Devedjian, Pascal Chaine, France Woimant, and James A. Duce each declare no potential conflicts of interest.

David Devos served on the Scientific Advisory Board for Novartis, Aguettant, Orkyn, Alzprotect, Apopharma. He has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia.

Caroline Moreau has served on the Scientific Advisory Board for Aguettant and Abbvie. She has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia.

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This article does not contain any studies with human or animal subjects performed by any of the authors. This article reports results from studies performed in animals and humans.

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This article is part of the Topical Collection on Neurologic Manifestations of Systemic Disease

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Poujois, A., Devedjian, JC., Moreau, C. et al. Bioavailable Trace Metals in Neurological Diseases. Curr Treat Options Neurol 18, 46 (2016). https://doi.org/10.1007/s11940-016-0426-1

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