Skip to main content
Journal cover image

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

Publication ,  Journal Article
Keeler, AM; Zieger, M; Todeasa, SH; McCall, AL; Gifford, JC; Birsak, S; Choudhury, SR; Byrne, BJ; Sena-Esteves, M; ElMallah, MK
Published in: Hum Gene Ther
January 2019

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-GaaTm1Rabn/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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

January 2019

Volume

30

Issue

1

Start / End Page

57 / 68

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Treatment Outcome
  • Prognosis
  • Muscle, Skeletal
  • Mice, Transgenic
  • Mice
  • Immunohistochemistry
  • Humans
  • Glycogen Storage Disease Type II
  • Glycogen
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Keeler, A. M., Zieger, M., Todeasa, S. H., McCall, A. L., Gifford, J. C., Birsak, S., … ElMallah, M. K. (2019). Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease. Hum Gene Ther, 30(1), 57–68. https://doi.org/10.1089/hum.2018.016
Keeler, Allison M., Marina Zieger, Sophia H. Todeasa, Angela L. McCall, Jennifer C. Gifford, Samantha Birsak, Sourav R. Choudhury, Barry J. Byrne, Miguel Sena-Esteves, and Mai K. ElMallah. “Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease.Hum Gene Ther 30, no. 1 (January 2019): 57–68. https://doi.org/10.1089/hum.2018.016.
Keeler AM, Zieger M, Todeasa SH, McCall AL, Gifford JC, Birsak S, et al. Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease. Hum Gene Ther. 2019 Jan;30(1):57–68.
Keeler, Allison M., et al. “Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease.Hum Gene Ther, vol. 30, no. 1, Jan. 2019, pp. 57–68. Pubmed, doi:10.1089/hum.2018.016.
Keeler AM, Zieger M, Todeasa SH, McCall AL, Gifford JC, Birsak S, Choudhury SR, Byrne BJ, Sena-Esteves M, ElMallah MK. Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease. Hum Gene Ther. 2019 Jan;30(1):57–68.
Journal cover image

Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

January 2019

Volume

30

Issue

1

Start / End Page

57 / 68

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Treatment Outcome
  • Prognosis
  • Muscle, Skeletal
  • Mice, Transgenic
  • Mice
  • Immunohistochemistry
  • Humans
  • Glycogen Storage Disease Type II
  • Glycogen