Rapid transcellular hepatic copper depletion by ARBM-101 rescues severe liver damage in Wilson disease rodents
Year: 2025
Type: article
Abstract: In Wilson disease (WD), excess copper provokes hepatocyte death due to impaired copper excretion, ultimately causing either acute or chronic liver damage. Current therapeutic compounds fail to reduce hepatic copper near to physiological levels, leaving lifelong, several times daily treatment as the only choice for patients. We have previously shown that a bacteria-derived methanobactin, termed ARBM-101, most efficiently depleted excess liver copper in still healthy WD rats. Here we report, for the first time, that mechanistically this is due to endosomal/lysosomal/exosomal trafficking of ARBM-101 in WD hepatocytes, allowing for copper mass excretion via the biliary/fecal route. We further show that such liver copper excretion occurs within minutes in vivo to detect copper-bound ARBM-101 in feces. This efficacy allows for specialized treatment regimen to rescue acute liver failure in WD rats. Moreover, also shown for the first time, it avoids fibrosis development in WD mice. Thus, judging from the results in two rodent species and human hepatocytes, this study advocates the development of ARBM-101 for WD therapy.
Source: Biomedicine & Pharmacotherapy
Authors: Jonas Engler, Eun-Jung Kim, Dasol Kim, Noreene M. Shibata, Emilie Munk Lynderup, Mikkel H. Vendelbo, Banu Akdogan, Judith Sailer, Adriana Fontes, Carola Eberhagen, Tamara Rieder, Quirin Reinold, Hongjae Lee, Dongsik Park, Chunwon Jung, Weonbin Im, Susanne I. Wudy, Karin Kleigrewe, Stefan Engelhardt, Alan A. DiSpirito, Thomas Damgaard Sandahl, Valentina Medici, So-Young Eun, Hans Zischka
Language: English
Topic: Trace Elements in Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,610
OpenAlex ID: W4417008221