Perspectives of Wilson’s disease treatment

Abstract

Objectives. Wilson’s disease (WD) is a genetic, neurodegenerative disorder caused by copper metabolism disturbances with subsequent pathological copper accumulation in organs and tissues (mainly liver and brain) with their secondary damage and clinical symptoms related to affected organs. The treatment of the disease is based on medications leading to negative body copper balance, i.e. (1) decreasing absorption of copper from the digestive tract (zinc salts); (2) increasing the copper excretion with urine (chelators: d-penicillamine, trientine, dimercaprol); and (3) liver transplant in specific clinical situations (acute liver failure, liver cirrhosis decompensation despite treatment). The article aims to review the available literature concerning the current research directions in WD treatment. Literature review. During the space of last years, intensive research into the new treatment of WD has started, including: (1) new pharmacological agents (modified thermostable trientine, trientine with delivery system to central nervous system, molybdenum salts, methanobactin, and others); (2) gene therapy; and (3) cells therapy (hepatocytes transplant). We conducted a targeted literature review of PubMed articles written in English, using the following search terms: “Wilson’s disease,” “treatment perspectives,” and “gene therapy.” Reviews, original articles, randomised controlled trials, meta-analyses, book chapters, and abstracts published up to April 2021 were included. Below, we present a narrative synthesis of the extracted data. Conclusions. Currently, chelators, medications decreasing absorption of copper from the digestive tract, and liver transplant are the treatment methods recommended by international societies as a WD treatment. Among the studies on new therapies for WD, the research with tetrathiomolybdate bis-choline is the most advanced and promising. Great hope can be associated with gene therapy.