Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin

Abstract

Wilson’s disease (WD) is a rare inherited genetic disorder caused by lost-offunction mutations in the ATP7B gene. ATP7B protein dysfunction causes failure of copper metabolism and consequent accumulation of cytotoxic copper in a variety of tissues especially the liver and brain. Curcumin is a natural polyphenolic compound extracted from Curcuma longa plants that has been studied extensively and proven to have anti-inflammatory, antioxidative and hepatoprotective activities.

This study evaluated the therapeutic efficacy of the liposome encapsulated form of curcumin in both a cell and animal model of WD. The results revealed that treatment with liposome-encapsulated curcumin inhibited cell death induced by copper chloride (CuCl2) of hepatocyte-like cells differentiated from WD patientspecific induced pluripotent stem cells (iPSCs). Also, when administered to 8-week-old Atp7b-/- WD mice, hepatosplenomegaly improved significantly along with reduced AST and ALT levels, improved serum lipid profiles, reduced inflammatory cytokines, attenuated liver inflammation and fibrosis due to inhibited excretion of HMGB-1 protein, one of the initiators of an inflammatory response. Hepatic copper and copper excreted in urine and feces were nonetheless not significantly changed.

These results indicated a therapeutic effect of liposome-encapsulated curcumin to ameliorate liver injury and improve liver function in WD via its anti-inflammatory and anti-fibrotic effects. This agent offers potential as a preventive therapy in patients with WD.