Pompe disease is an autosomal recessive genetic disorder characterized by a 
deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid 
α-glucosidase (GAA)). Cardiac dysfunction and respiratory muscle weakness are 
primary features of this disorder. To attenuate the progressive and rapid 
accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa 
(-/-) mice were administered a single systemic injection of rAAV2/9-DES-hGAA 
(AAV9-DES) or bimonthly injections of recombinant human GAA (enzyme replacement 
therapy (ERT)). Assessment of cardiac function and morphology was measured 1 and 
3 months after initiation of treatment while whole-body plethysmography and 
diaphragmatic contractile function was evaluated at 3 months post-treatment in 
all groups. Gaa (-/-) animals receiving either AAV9-DES or ERT demonstrated a 
significant improvement in cardiac function and diaphragmatic contractile 
function as compared to control animals. AAV9-DES treatment resulted in a 
significant reduction in cardiac dimension (end diastolic left ventricular 
mass/gram wet weight; EDMc) at 3 months postinjection. Neither AAV nor ERT 
therapy altered minute ventilation during quiet breathing (eupnea). However, 
breathing frequency and expiratory time were significantly improved in AAV9-DES 
animals. These results indicate systemic delivery of either strategy improves 
cardiac function but AAV9-DES alone improves respiratory parameters at 3 months 
post-treatment in a murine model of Pompe disease.