Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease

UMMS Affiliation

Division of Pulmonary Medicine, Department of Pediatrics; Horae Gene Therapy Center; Department of Neurology

Publication Date


Document Type



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Enzymes and Coenzymes | Genetics and Genomics | Nervous System Diseases | Nutritional and Metabolic Diseases | Therapeutics


Pompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and the central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease, since a single systemic injection may correct both muscle and CNS pathologies. Using the Pompe mouse (B6;129-Gaa(Tm1Rabn)/J), this study sought to explore if AAVB1, a newly engineered vector with a high affinity for muscle and CNS, reduces systemic weakness and improves survival in adult mice. Three-month-old Gaa(-/-) animals were injected with either AAVB1 or AAV9 vectors expressing GAA and tissues were harvested 6 months later. Both AAV vectors prolonged survival. AAVB1-treated animals had a robust weight gain compared to the AAV9-treated group. Vector genome levels, GAA enzyme activity, and histological analysis indicated that both vectors transduced the heart efficiently, leading to glycogen clearance, and transduced the diaphragm and CNS at comparable levels. AAVB1-treated mice had higher GAA activity and greater glycogen clearance in the tongue. Finally, AAVB1-treated animals showed improved respiratory function comparable to wild-type animals. In conclusion, AAVB1-GAA offers a promising therapeutic option for the treatment of muscle and CNS in Pompe disease.


AAV9, AAVB1, Pompe disease, glycogen, respiratory

DOI of Published Version



Hum Gene Ther. 2018 Jul 25. doi: 10.1089/hum.2018.016. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Human gene therapy

Related Resources

Link to Article in PubMed

PubMed ID