Adeno-associated virus expressing a blood-brain barrier-penetrating enzyme improves GM1 gangliosidosis in a preclinical model.

ABSTRACT: GM1 gangliosidosis is a lysosomal storage disorder (LSD) caused by genetic defects in lysosomal β-galactosidase (β-gal). The primary substrate of β-gal is GM1 ganglioside (GM1), a sialylated glycosphingolipid abundant in the central nervous system (CNS). Deficiency in β-gal causes GM1 to accumulate in neural cells, leading to a rapid decline in psychomotor functions, seizures, and premature death. There is currently no therapy available. Although enzyme replacement therapy has been approved for other LSDs, its effects on the CNS are limited owing to the blood-brain barrier (BBB). Here, we assessed the therapeutic efficacy of a systemic infusion of an adeno-associated virus vector carrying a gene expressing a BBB-penetrable enzyme under the control of a liver-specific promoter in GM1 gangli

SUBMITTER: Matsushima SK 

PROVIDER: S-EPMC12165788 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature