Shribman, S;
Poujois, A;
Bandmann, O;
Czlonkowska, A;
Warner, TT;
(2021)
Wilson's disease: update on pathogenesis, biomarkers and treatments.
Journal of Neurology, Neurosurgery and Psychiatry
, 92
(10)
pp. 1053-1061.
10.1136/jnnp-2021-326123.
Preview |
Text
Shribman_Revised_manuscript_clean.pdf - Accepted Version Download (712kB) | Preview |
Abstract
Wilson’s disease is an autosomal–recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson’s disease from the neurological perspective, with a focus on recent advances. The genetic and molecular mechanisms associated with ATP7B dysfunction have been well characterised, but despite extensive efforts to identify genotype–phenotype correlations, the reason why only some patients develop neurological or psychiatric features remains unclear. We discuss pathological processes through which copper accumulation leads to neurodegeneration, such as mitochondrial dysfunction, the role of brain iron metabolism and the broader concept of selective neuronal vulnerability in Wilson’s disease. Delayed diagnoses continue to be a major problem for patients with neurological presentations. We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson’s disease, before discussing future directions for translational research.
| Type: | Article |
|---|---|
| Title: | Wilson's disease: update on pathogenesis, biomarkers and treatments |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/jnnp-2021-326123 |
| Publisher version: | https://doi.org/10.1136/jnnp-2021-326123 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Psychiatry, Surgery, Neurosciences & Neurology, Wilson's disease, CLINICAL PRESENTATION, COPPER, DIAGNOSIS, MODEL, TETRATHIOMOLYBDATE, EPIDEMIOLOGY, PHENOTYPE, SYMPTOMS, ATPASE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10136191 |
Archive Staff Only
 |
View Item |
