Evaluation of efficacy and safety of AAV8-ΔC4ATP7B gene therapy in a mutant mouse model of Wilson's disease.

ABSTRACT: Wilson's disease (WD) is an autosomal recessive disorder caused by pathogenic variants in the ATP7B gene, resulting in the toxic accumulation of copper (Cu). Impaired Cu homeostasis in WD is characterized by low serum ceruloplasmin, excess hepatic Cu, and elevated urinary Cu. WD often presents with hepatic and/or neurological diseases and is fatal if untreated. Adeno-associated virus (AAV)-mediated gene therapy holds promise for WD, but challenges remain in efficacy and safety. Here, we established an Atp7b R780L knockin (KI) mouse model corresponding to the human ATP7B R778L variant and investigated the therapeutic efficacy and safety of liver-targeted AAV8-mediated ATP7B (AAV8-ΔC4ATP7B) gene therapy in this model. The results demonstrated the Atp7b

SUBMITTER: Zeng C 

PROVIDER: S-EPMC11919453 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature