Preclinical pharmacology and safety studies to support an AAV9 NGLY1 gene therapy clinical trial for the treatment of NGLY1 deficiency.

ABSTRACT: GS-100 is an AAV9 gene replacement therapy for the treatment of N-glycanase 1 (NGLY1) deficiency, an ultra-rare, recessive disorder characterized by developmental delay, intellectual disability, hyperkinetic movement disorder, elevated liver enzymes, (hypo)alacrima, and peripheral neuropathy. In pharmacology studies using Ngly1 ^-/- rats, intracerebroventricular (i.c.v.) administration of GS-100 showed dose-dependent biodistribution, increased hNGLY1 mRNA expression, reduced disease biomarker N-acetylglucosamine-asparagine (GNA), improved motor function, and prevented phenotype progression. Reductions in GNA within central nervous system (CNS) tissues and cerebrospinal fluid (CSF) correlated significantly with improvements, suggesting that CSF GNA may serve as a cli

SUBMITTER: Zhu L 

PROVIDER: S-EPMC12272873 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature