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Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.

Publication ,  Journal Article
Han, S-O; Li, S; Everitt, JI; Koeberl, DD
Published in: Hum Gene Ther
July 2019

Gene therapy for Pompe disease with adeno-associated virus (AAV) vectors has advanced into early phase clinical trials; however, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up acid α-glucosidase (GAA), has impeded the efficacy of Pompe disease gene therapy. Long-acting selective β2 receptor agonists previously enhanced the CI-MPR expression in muscle. In this study we have evaluated the selective β2 agonist salmeterol in GAA knockout mice in combination with an AAV vector expressing human GAA specifically in the liver. Quadriceps glycogen content was significantly decreased by administration of the AAV vector with salmeterol, in comparison with the AAV vector alone (p < 0.01). Importantly, glycogen content of the quadriceps was reduced to its lowest level by the combination of AAV vector and salmeterol administration. Rotarod testing revealed significant improvement following treatment, in comparison with untreated mice, and salmeterol improved wirehang performance. Salmeterol treatment decreased abnormalities of autophagy in the quadriceps, as shown be lower LC3 and p62. Vector administration reduced the abnormal vacuolization and accumulation of nuclei in skeletal muscle. Thus, salmeterol could be further developed as adjunctive therapy to improve the efficacy of liver depot gene therapy for Pompe disease.

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Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

July 2019

Volume

30

Issue

7

Start / End Page

855 / 864

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Salmeterol Xinafoate
  • Receptor, IGF Type 2
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Glycogen Storage Disease Type II
  • Genetic Vectors
  • Genetic Therapy
  • Gene Transfer Techniques
 

Citation

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Han, S.-O., Li, S., Everitt, J. I., & Koeberl, D. D. (2019). Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease. Hum Gene Ther, 30(7), 855–864. https://doi.org/10.1089/hum.2018.197
Han, Sang-Oh, Songtao Li, Jeffrey I. Everitt, and Dwight D. Koeberl. “Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.Hum Gene Ther 30, no. 7 (July 2019): 855–64. https://doi.org/10.1089/hum.2018.197.
Han S-O, Li S, Everitt JI, Koeberl DD. Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease. Hum Gene Ther. 2019 Jul;30(7):855–64.
Han, Sang-Oh, et al. “Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.Hum Gene Ther, vol. 30, no. 7, July 2019, pp. 855–64. Pubmed, doi:10.1089/hum.2018.197.
Han S-O, Li S, Everitt JI, Koeberl DD. Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease. Hum Gene Ther. 2019 Jul;30(7):855–864.
Journal cover image

Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

July 2019

Volume

30

Issue

7

Start / End Page

855 / 864

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Salmeterol Xinafoate
  • Receptor, IGF Type 2
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Glycogen Storage Disease Type II
  • Genetic Vectors
  • Genetic Therapy
  • Gene Transfer Techniques