Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia.

ABSTRACT: GRN mutations leading to progranulin haploinsufficiency can cause frontotemporal dementia. AVB-101, an investigational gene therapy comprising an adeno-associated virus construct expressing codon-optimized human GRN under a neuronal promoter, was delivered intrathalamically to mice, sheep, and non-human primates. AVB-101 reversed pathology in Grn ^-/- mice and achieved widespread cortical biodistribution in sheep brain, with human progranulin protein detected in the majority of prefrontal cortical neurons. Conversely, human progranulin was undetectable in sheep cortical neurons following intra-cisterna magna administration of AVB-101 or adeno-associated viruses containing progranulin under a ubiquitous promoter. AVB-101 was well tolerated in cynomolgus macaqu

SUBMITTER: Lee YB 

PROVIDER: S-EPMC12651635 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature