Biodistribution Analysis of Adeno-Associated Viral Vectors of Serotypes 9 and rh.10 Encoding Arylsulfatase A Following Prior Immunization with Serotype 9 in Pigs

Abstract

Lysosomal storage diseases are a group of inherited disorders caused by lysosomal dysfunction, impairing cellular metabolic enzymes, signaling pathways, and other biological processes. Among them is metachromatic leukodystrophy (MLD) associated with arylsulfatase A (ARSA) deficiency, which leads to the accumulation of sulfatides and the destruction of myelin sheaths in the nervous system. This study evaluates the therapeutic efficacy of adeno-associated viruses (AAVs) in treating neurodegenerative diseases such as MLD. The biodistribution and safety of AAV9-ARSA and AAVrh.10-ARSA vectors following prior immunization in pigs were shown. The immune aspects of AAV-based gene therapy were outlined. Its potential efficacy and durability limitations were discussed.

Keywords

• metachromatic leukodystrophy
• arylsulfatase
• gene therapy
• neurodegenerative disease