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

Human Gene Therapy
Sang-Oh HanDwight D Koeberl

Abstract

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...Continue Reading

References

Oct 22, 2003·Molecular Genetics and Metabolism·N RabenP H Plotz
Dec 9, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Baodong SunDwight D Koeberl
Jul 12, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Luis M FrancoDwight D Koeberl
Oct 1, 2007·Therapeutic Advances in Respiratory Disease·Mario Cazzola, Maria Gabriella Matera
Mar 17, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marc NicolinoPriya S Kishnani
Aug 20, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Baodong SunDwight D Koeberl
Sep 19, 2009·Dysphagia·Harrison N JonesPriya S Kishnani
Sep 25, 2009·Molecular Genetics and Metabolism·Priya S KishnaniY-T Chen
Feb 5, 2010·Journal of Pediatric Ophthalmology and Strabismus·Tammy L YanovitchPriya S Kishnani
Jun 4, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suhrad G BanugariaPriya S Kishnani
Dec 14, 2011·Molecular Genetics and Metabolism·Dwight D KoeberlPriya S Kishnani
May 19, 2012·Cell Death and Differentiation·A C NascimbeniM Sandri
Sep 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Songtao LiDwight D Koeberl
Jan 21, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dwight D KoeberlPriya S Kishnani
Jan 23, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benjamin L FarahDwight D Koeberl
Nov 11, 2014·Human Gene Therapy·Sang-Oh HanDwight Koeberl
Jan 1, 2014·Molecular Therapy. Methods & Clinical Development·Gensheng WangDwight D Koeberl
Mar 28, 2016·Molecular Genetics and Metabolism·Sang-Oh HanDwight D Koeberl
Sep 7, 2016·Autonomic Neuroscience : Basic & Clinical·Eric J MartinLinda F Hayward
Mar 28, 2017·Molecular Therapy. Methods & Clinical Development·Sang-Oh HanDwight Koeberl
Dec 1, 2017·Science Translational Medicine·Francesco PuzzoFederico Mingozzi
Jul 22, 2018·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dwight D KoeberlPriya S Kishnani

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Citations

Jul 13, 2019·Human Gene Therapy·Pasqualina Colella, Federico Mingozzi
Dec 5, 2019·Journal of Neuromuscular Diseases·S M SalabarriaM Corti
Dec 4, 2019·Molecular Genetics and Metabolism·Benjamin L FarahDwight D Koeberl
Dec 23, 2020·International Journal of Molecular Sciences·Aitana Almodóvar-PayáTomàs Pinós
Dec 12, 2020·Frontiers in Molecular Biosciences·Mariola J Edelmann, Gustavo H B Maegawa
May 12, 2021·Journal of Human Genetics·Manuel A ViamontePeter B Kang
Jan 8, 2020·Molecular Therapy. Methods & Clinical Development·Sang-Oh HanDwight D Koeberl

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Methods Mentioned

BETA
protein assay
PCR

Software Mentioned

GraphPad
Image Lab
GraphPad Prism5

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