Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2017; 23(30): 5451-5456
Published online Aug 14, 2017. doi: 10.3748/wjg.v23.i30.5451
Wilson’s disease: Prospective developments towards new therapies
Giusy Ranucci, Roman Polishchuck, Raffaele Iorio
Giusy Ranucci, Raffaele Iorio, Department of Translational Medical Science, Section of Pediatric, University Federico II, 80131 Naples, Italy
Roman Polishchuck, Telethon Institute of Genetics and Medicine, 80078 Pozzuoli (NA), Italy
Author contributions: Ranucci G, Polishchuck R and Iorio R contributed equally to the article’s design, conception and writing.
Conflict-of-interest statement: All authors declare they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Raffaele Iorio, MD, Associate Professor, Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via Pansini 5, 80131 Naples, Italy. riorio@unina.it
Telephone: +39-081-7464337 Fax: +39-081-7464337
Received: February 3, 2017
Peer-review started: February 8, 2017
First decision: March 6, 2017
Revised: April 11, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: August 14, 2017
Abstract

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in the ATP7B gene. A clear demand for novel WD treatment strategies has emerged. Although therapies using zinc salts and copper chelators can effectively cure WD, these drugs exhibit limitations in a substantial pool of WD patients who develop intolerance and/or severe side effects. Several lines of research have indicated intriguing potential for novel strategies and targets for development of new therapies. Here, we review these new approaches, which comprise correction of ATP7B mutants and discovery of new compounds that circumvent ATP7B-deficiency, as well as cell and gene therapies. We also discuss whether and when these new therapeutic strategies will be translated into clinical use, according to the key requirements for clinical trials that remain to be met. Finally, we discuss the hope for the current rapidly developing research on molecular mechanisms underlying WD pathogenesis and for the related potential therapeutic targets to provide a solid foundation for the next generation of WD therapies that may lead to an effective, tolerable and safe cure.

Keywords: ATP7B, Stem cell-derived hepatocyte like cells, Methanobactin, Heat shock protein 70, p38, JNK, Correctors, Translational medicine, Precision medicine

Core tip: Hepatocytes derived from human-induced pluripotent stem cells hold great promise for the drug discovery process, especially for Wilson’s disease (WD). Therapeutic approaches offering correction of the ATP7B mutant function and/or less toxic suppression of copper accumulation are promising and could be available shortly. In particular, protein quality control components and their regulatory networks represent attractive new targets for WD-causing mutant correction. Cell and gene therapies, however, will require more studies before they can be considered for clinical trials. A key goal for WD advancement is international cooperation of specialized centers to overcome limited availability of patients for study.