High value of ⁶⁴Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson's disease.

ABSTRACT: Wilson's disease (WD) is an inherited disorder of copper metabolism associated with mutations in ATP7B gene. We have shown that the administration of an adeno-associated vector (AAV) encoding a mini version of human ATP7B (VTX-801) provides long-term correction of copper metabolism in a murine WD model. In preparation of a future clinical trial, we have evaluated by positron emission tomography (PET) the value of ⁶⁴Cu biodistribution, excretion pattern, and blood kinetics as pharmacodynamic biomarkers of VTX-801 effects. Six-week-old WD mice were injected intravenously with increasing doses of VTX-801 and 3 weeks or 3 months later with [⁶⁴Cu]CuCl₂. Untreated WD and wild-type (WT) mice were included as controls. Control WD mice showed increased hepati

SUBMITTER: Murillo O 

PROVIDER: S-EPMC9234538 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature