Wilson's disease: Prospective developments towards new therapies.

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.