Effective gene therapy for metachromatic leukodystrophy achieved with minimal lentiviral genomic integrations.

ABSTRACT: Metachromatic leukodystrophy (MLD) is a fatal lysosomal storage disease characterized by the deficient enzymatic activity of arylsulfatase A (ARSA). Combined autologous hematopoietic stem cell transplantion (HSCT) with lentiviral (LV)-based gene therapy has great potential to treat MLD. Achieving the optimal balance between high enzyme production for therapeutic efficacy and maintaining a low vector copy number (VCN) is crucial. Insufficient enzyme levels can lead to the progression of motor symptoms, undermining treatment goals. Conversely, elevated VCN increases the risk of genotoxicity, which poses safety concerns, and contributes to higher production costs, making the therapy less accessible. Striking this balance is essential to maximize clinical benefit while minimizing risks and cos

SUBMITTER: Tricoli L 

PROVIDER: S-EPMC11960508 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature