Adeno-associated virus serotype 1-based gene therapy for FTD caused by GRN mutations.

ABSTRACT:

Objective

Dominant loss-of-function mutations in the gene encoding the lysosomal protein, progranulin, cause 5-10% of frontotemporal dementia cases. As progranulin undergoes secretion and endocytosis, a small number of progranulin-expressing cells can potentially supply the protein to the entire central nervous system. Thus, gene therapy is a promising treatment approach.

Methods

We evaluated adeno-associated viral vector administration into the cerebrospinal fluid as a minimally invasive approach to deliver the granulin gene to the central nervous system in a murine disease model and nonhuman primates.

Results

In progranulin-deficient mice, vector delivery into the lateral cerebral ventricles increased progranulin levels in the cerebrospinal fluid and normalized hist

SUBMITTER: Hinderer C 

PROVIDER: S-EPMC7545603 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature