Cross-species efficacy of AAV-mediated ARSA replacement for metachromatic leukodystrophy.

ABSTRACT: Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder caused by mutations in the arylsulfatase A (ARSA) gene, resulting in lower sulfatase activity and the toxic accumulation of sulfatides in the central and peripheral nervous system. Children account for 70% of cases and become progressively disabled, with death occurring within 10 years of disease onset. Gene therapy approaches to restore ARSA expression via adeno-associated virus (AAV) vectors have been promising but hampered by limited brain biodistribution. We report the development of an engineered capsid, AAV.GMU01, demonstrating superior biodistribution and transgene expression in the central nervous system of nonhuman primates (NHPs). Next, we show that AAV.GMU01-ARSA-treated MLD mice exhibit pers

SUBMITTER: Ramachandran S 

PROVIDER: S-EPMC12352910 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature