106 In Vivo Site Specific Delivery of Nanoparticles to Airway Epithelium Monitored by Scintigraphy Molecular Therapy Volume 19, Supplement 1, May 2011 Copyright © The American Society of Gene & Cell T[.]
LUNG AND RESPIRATORY DISEASE GENE & CELL THERAPY 104 Intrathoracic Administration of AAV9 Reverses Neural and Cardiorespiratory Dysfunction in Pompe Disease Darin J Falk,1 Cathryn S Mah,1 Meghan S Soustek,1 Kun-Ze Lee,2 Denise A Cloutier,1 Mai K Elmallah,1 Kirsten E Erger,1 Thomas J Conlon,1 David D Fuller,2 Barry J Byrne.1 Pediatrics & Powell Gene Therapy Center, University of Florida, Gainesville, FL; 2Physical Therapy, University of Florida, Gainesville, FL Pompe disease is an autosomal recessive disorder resulting from deficiency in acid alpha glucosidase (GAA) Deficiency of lysosomal GAA results in cardiac, skeletal muscle and central nervous system (CNS) pathology Enzyme replacement therapy (ERT) is the current standard of care and has been shown to partially correct cardiac and skeletal muscle dysfunction However, recombinant enzyme is unable to penetrate the blood brain barrier to target CNS pathology Here we tested the hypothesis that intrathoracic administration of AAV9GAA driven by either a viral promoter (CMV) or a unique tissue specific promoter (Desmin; DES), will express the GAA gene in both striated muscle and the CNS in adult Gaa-/- mice, thereby enhancing both cardiac and respiratory function Mice were studied months after intrathoracic delivery of GAA via AAV9-DES or AAV9-CMV Cardiac MRI revealed significant improvement in ejection fraction (AAV9-DES: 13.2±5.5% and AAV9-CMV: 11.0±5.2%, p