Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.

ABSTRACT: Absence of functional acid-α-glucosidase (GAA) leads to early-onset Pompe disease with cardiorespiratory and neuromuscular failure. A novel Pompe rat model (Gaa ^-/-) was used to test the hypothesis that neonatal gene therapy with adeno-associated virus serotype 9 (AAV9) restores cardiorespiratory neuromuscular function across the lifespan. Temporal vein administration of AAV9-DES-GAA or sham (saline) injection was done on post-natal day 1; rats were studied at 6-12 months old. Whole-body plethysmography showed that reduced inspiratory tidal volumes in Gaa ^-/- rats were corrected by AAV-GAA treatment. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI) revealed that AAV-GAA treatment normalized diaphragm muscle glycogen as well a

SUBMITTER: Fuller DD 

PROVIDER: S-EPMC11702543 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature