Gene therapy with secreted acid alpha-glucosidase rescues Pompe disease in a novel mouse model with early-onset spinal cord and respiratory defects.

ABSTRACT:

Background

Pompe disease (PD) is a neuromuscular disorder caused by deficiency of acidalpha-glucosidase (GAA), leading to motor and respiratory dysfunctions. Available Gaa knock-out (KO) mouse models do not accurately mimic PD, particularly its highly impaired respiratory phenotype.

Methods

Here we developed a new mouse model of PD crossing Gaa KO^B6;129 with DBA2/J mice. We subsequently treated Gaa KO^DBA2/J mice with adeno-associated virus (AAV) vectors expressing a secretable form of GAA (secGAA).

Findings

Male Gaa KO^DBA2/J mice present most of the key features of the human disease, including early lethality, severe respiratory impairment, cardiac hypertrophy and muscle weakness. Transcriptome analyses of Gaa KO^DBA2/J, comp

SUBMITTER: Colella P 

PROVIDER: S-EPMC7553357 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature