Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice.

ABSTRACT: Niemann-Pick disease, type C1 (NPC1) is a rare, fatal neurodegenerative disorder caused by pathological variants in NPC1, which encodes a lysosomal cholesterol transport protein. There are no FDA approved treatments for this disorder. Both systemic and central nervous system delivery of AAV9-hNPC1 have shown significant disease amelioration in NPC1 murine models. To assess the impact of dose and window of therapeutic efficacy in Npc1 ^m1N mice, we systemically administered three different doses of AAV9-hNPC1 at 4 weeks old and the medium dose at pre-, early, and post-symptomatic timepoints. Higher vector doses and treatment earlier in life were associated with enhanced transduction in the nervous system and resulted in significantly increased li

SUBMITTER: Mylvara AV 

PROVIDER: S-EPMC11185674 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature