Skip to main content

Advertisement

SpringerLink
Log in

Correction of glycogenosis type 2 by muscle-specific lentiviral vector

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Glycogen storage disease type II (GSDII) or Pompe disease is an inherited disease of glycogen metabolism caused by a lack of functional lysosomal acid α-glucosidase (GAA). Affected individuals store glycogen in lysosomes resulting in fatal hypertrophic cardiomyopathy and respiratory failure in the most severe form. We investigated for the first time the use of lentiviral vectors to correct the GSDII phenotype in human and murine GAA-deficient cells. Fibroblasts from infantile and adult GSDII patients were efficiently transduced by a GAA-expressing lentiviral vector placed under the control of the strong MND promoter, leading to a complete restoration of enzymatic activity. We also developed a muscle-specific lentiviral vector based on the synthetic C5–12 promoter and tested it on deficient myogenic satellite cells derived from a GSDII mouse model. GAA was expressed as a correctly processed protein allowing a complete enzymatic and metabolic correction in myoblasts and differentiated myotubes, as well as a significant mannose-6-phosphate (M6P)-dependent secretion reuptake by naive cells. Transduced cells showed lysosomal glycogen clearance, as demonstrated by electron microscopy. These results form the basis for a therapeutic approach of GSDII using lentiviral vector-mediated gene transfer into muscle stem cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.

Similar content being viewed by others

References

  • Bijvoet, A. G.; van de Kamp, E. H.; Kroos, M. A.; Ding, J. H.; Yang, B. Z.; Visser, P.; Bakker, C. E.; Verbeet, M. P.; Oostra, B. A.; Reuser, A. J.; Van der Ploeg, A. T. Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease. Hum. Mol. Genet 7: 53–62; 1998 doi:10.1093/hmg/7.1.53.

    Article  PubMed  CAS  Google Scholar 

  • Cavazzana-Calvo, M.; Fischer, A. Gene therapy for severe combined immunodeficiency: are we there yet? J. Clin. Invest. 117: 1456–1465; 2007 doi:10.1172/JCI30953.

    Article  PubMed  CAS  Google Scholar 

  • Chang, A. H.; Sadelain, M. The genetic engineering of hematopoietic stem cells: the rise of lentiviral vectors, the conundrum of the LTR, and the promise of lineage-restricted vectors. Mol. Ther. 15: 445–456; 2007 doi:10.1038/sj.mt.6300060.

    Article  PubMed  CAS  Google Scholar 

  • Coffin, J. M.; Hugues, S. H.; Varmus, H. E. Retroviruses. Cold Spring Harbour Laboratory Press, Cold Spring Harbor, New York;1997.

    Google Scholar 

  • D’Ancona, G. G.; Wurm, J.; Croce, C. M. Genetics of type II glycogenosis: assignment of the human gene for acid alpha-glucosidase to chromosome 17. Proc. Natl. Acad. Sci. USA 76: 4526–4529; 1979 doi:10.1073/pnas.76.9.4526.

    Article  PubMed  CAS  Google Scholar 

  • Draghia-Akli, R.; Ellis, K. M.; Hill, L. A.; Malone, P. B.; Fiorotto, M. L. High-efficiency growth hormone-releasing hormone plasmid vector administration into skeletal muscle mediated by electroporation in pigs. FASEB J 17: 526–528; 2003.

    PubMed  CAS  Google Scholar 

  • Fraites, T. J. Jr.; Schleissing, M. R. R.; Shanely, A.; Walter, G. A.; Coutier, D. A.; Zolotukhin, I.; Pauly, D. F.; Raben, N.; Plotz, P. H.; Powers, S. K.; Kessler, P. D.; Byrne, B. J. Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors. Mol. Ther 5: 571–578; 2002 doi:10.1006/mthe.2002.0580.

    Article  PubMed  CAS  Google Scholar 

  • Franco, L. M.; Sun, B.; Yang, X.; Bird, A.; Zhang, H.; Schneider, A.; Brown, T.; Young, S. P.; Clay, T. M.; Amalfitano, A.; Chen, Y. T.; Koeberl, D. D. Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol. Ther 12: 876–884; 2005 doi:10.1016/j.ymthe.2005.04.024.

    Article  PubMed  CAS  Google Scholar 

  • Halene, S.; Wang, L.; Cooper, R. M.; Bockstoce, D. C.; Robbins, P. B.; Khon, D. B. Improved expression in hematopoietic and lymphoid cells in mice after transplantation of bone marrow transduced with a modified retroviral vector. Blood 94: 3349–3357; 1999.

    PubMed  CAS  Google Scholar 

  • Hirschhorn, R.; Reuser, A. J. J. Glycogen storage disease type II: acid α-glucosidase (acid maltase) deficiency. In: Scriver, C. R.; Baudet, A. L.; Sly W. S.; Valle, D. (eds) The metabolic and molecular bases of inherited diseases. McGraw-Hill, New York, pp 3389–3420; 2001.

    Google Scholar 

  • Kafri, T.; Blomer, U.; Peterson, D. A.; Gage, F. H.; Verma, I. M. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat. Genet 17: 314–317; 1997 doi:10.1038/ng1197–314.

    Article  PubMed  CAS  Google Scholar 

  • Klinge, L.; Straub, V.; Neudorf, U.; Schaper, J.; Bosbach, T.; Gorlinger, K.; Wallot, M.; Richards, S.; Voit, T. Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial. Neuromuscul. Disord. 15: 24–31; 2005 doi:10.1016/j.nmd.2004.10.009.

    Article  PubMed  CAS  Google Scholar 

  • Katzin, L. W.; Amato, A. A. Pompe disease: a review of the current diagnosis and treatment recommendations in the era of enzyme replacement therapy. J. Clin. Neuromuscul. Dis 9: 421–431; 2008 doi:10.1097/CND.0b013e318176dbe4.

    Article  PubMed  Google Scholar 

  • Kishnani, P. S.; Corzo, D.; Nicolino, M.; Byrne, B.; Mandel, H.; Hwu, W. L.; Leslie, N.; Levine, J.; Spencer, C.; McDonald, M.; Li, J.; Dumontier, J.; Halberthal, M.; Chien, Y. H.; Hopkin, R.; Vijayaraghavan, S.; Gruskin, D.; Bartholomew, D.; van der Ploeg, A.; Clancy, J. P.; Parini, R.; Morin, G.; Beck, M.; De la Gastine, G. S.; Jokic, M.; Thurberg, B.; Richards, S.; Bali, D.; Davison, M.; Worden, M. A.; Chen, Y. T.; Wraith, J. E. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 9: 99–109; 2007 doi:10.1212/01.wnl.0000251268.41188.04.

    Article  CAS  Google Scholar 

  • Li, E.; Eastman, M.; Schwartz, R. J.; Draghia-Akli, R. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences. Nat. Biotechnol 17: 241–245; 1999 doi:10.1038/6981.

    Article  PubMed  CAS  Google Scholar 

  • Liu, C.; Bahnson, A. B.; Dunigan, J. T.; Watkins, S. C.; Barranger, J. A. Long-term expression and secretion of human glucocerebrosidase by primary murine and human myoblasts and differentiated myotubes. J. Mol. Med. 76: 773–781; 1998 doi:10.1007/s001090050279.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y. L.; Mingozzi, F.; Rodriguez-Colon, S. M.; Joseph, S.; Dobrzynski, E.; Suzuki, T.; High, K. A.; Herzog, R. W. Therapeutic levels of factor IX expression using a muscle-specific promoter and adeno-associated virus serotype 1 vector. Hum. Gene Ther 15: 783–792; 2004 doi:10.1089/1043034041648453.

    Article  PubMed  CAS  Google Scholar 

  • Martin-Touaux, E.; Puech, J. P.; Chateau, D.; Emiliani, C.; Kremer, E. J.; Raben, N.; Tancini, B.; Orlacchio, A.; Kahn, A.; Poenaru, L. Muscle as a putative producer of acid alpha-glucosidase for glycogenosis type II gene therapy.. Hum. Mol. Genet 11: 1637–1645; 2002 doi:10.1093/hmg/11.14.1637.

    Article  PubMed  CAS  Google Scholar 

  • Martiniuk, F.; Bodkin, M.; Tzall, S.; Hirschhorn, R. Isolation and partial characterization of the structural gene for human acid alpha glucosidase. DNA Cell Biol 10: 283–292; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Moreau-Gaudry, F.; Xia, P.; Jiang, G.; Perelman, N. P.; Bauer, G.; Ellis, J.; Surinya, K. H.; Mavilio, F.; Chen, C. K.; Malik, P. High-level erythroid-specific gene expression in primary human and murine hematopoietic cells with self-inactivating lentiviral vectors. Blood 98: 2664–2672; 2001 doi:10.1182/blood.V98.9.2664.

    Article  PubMed  CAS  Google Scholar 

  • Ott, M. G.; Seger, R.; Stein, S.; Siler, U.; Hoelzer, D.; Grez, M. Advances in the treatment of chronic granulomatous disease by gene therapy. Curr. Gene Ther. 7: 155–161; 2007 doi:10.2174/156652307780859044.

    Article  PubMed  CAS  Google Scholar 

  • Pinset, C.; Montarras, D. Cell biology: a laboratory handbook. Academic, San Diego1994.

    Google Scholar 

  • Queneville, S. P.; Chapdelaine, P.; Skuk, D.; Paradis, M.; Goulet, M.; Rousseau, J.; Xiao, X.; Garcia, L.; Tremblay, J. P. Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models. Mol. Ther. 15: 431–438; 2007 doi:10.1038/sj.mt.6300047.

    Article  CAS  Google Scholar 

  • Raben, N.; Danon, M.; Gilbert, A. L.; Dwivedi, S.; Collins, B.; Thurberg, B. L.; Mattaliano, R. J.; Nagaraju, K.; Plotz, P. H. Enzyme replacement therapy in the mouse model of Pompe disease. Mol. Genet Metab. 80: 159–169; 2003 doi:10.1016/j.ymgme.2003.08.022.

    Article  PubMed  CAS  Google Scholar 

  • Raben, N.; Nagaraju, K.; Lee, E.; Kessler, P.; Byrne, B.; Lee, L.; Lamarca, M.; King, C.; Ward, J.; Sauer, B.; Plotz, P. Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II.. J. Biol. Chem. 273: 19086–19092; 1998 doi:10.1074/jbc.273.30.19086.

    Article  PubMed  CAS  Google Scholar 

  • Richard, E.; Robert, E.; Cario-Andre, M.; Ged, C.; Geronimi, F.; Gerson, S. L.; de Verneuil, H.; Moreau-Gaudry, F. Hematopoietic stem cell gene therapy of murine protoporphyria by methylguanine-DNA-methyltransferase-mediated in vivo drug selection. Gene Ther. 11: 1638–1647; 2004 doi:10.1038/sj.gt.3302335.

    Article  PubMed  CAS  Google Scholar 

  • Schnepp, B. C.; Clark, K. R.; Klemanski, D. L.; Pacak, C. A.; Johnson, P. R. Genetic fate of recombinant adeno-associated virus vector genomes in muscle. J. Virol. 77: 3495–3504; 2003 doi:10.1128/JVI.77.6.3495-3504.2003.

    Article  PubMed  CAS  Google Scholar 

  • Sun, B.; Bird, A.; Young, S. P.; Kishnani, P. S.; Chen, Y. T.; Koeberl, D. D. Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance. Am. J. Hum. Genet. 81: 1042–1049; 2007 doi:10.1086/522236.

    Article  PubMed  CAS  Google Scholar 

  • Sun, B.; Zhang, H.; Benjamin, D. K. Jr; Brown, T.; Bird, A.; Young, S. P.; McVie-Wylie, A.; Chen, Y. T.; Koeberl, D. D. Enhanced efficacy of an AAV vector encoding chimeric, highly secreted acid alpha-glucosidase in glycogen storage disease type II. Mol. Ther. 14: 822–830; 2006 doi:10.1016/j.ymthe.2006.08.001.

    Article  PubMed  CAS  Google Scholar 

  • Sun, B.; Zang, H.; Franco, L. M.; Brown, T.; Bird, A.; Schneider, A.; Koeberl, D. D. Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter. Mol. Ther. 11: 889–898; 2005b doi:10.1016/j.ymthe.2005.01.012.

    Article  PubMed  CAS  Google Scholar 

  • Sun, B.; Zhang, H.; Franco, L. M.; Young, S. P.; Schneider, A.; Bird, A.; Amalfitano, A.; Chen, Y. T.; Koeberl, D. D. Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II.. Mol. Ther. 11: 57–65; 2005a doi:10.1016/j.ymthe.2004.10.004.

    Article  PubMed  CAS  Google Scholar 

  • Umapathysivam, K.; Hopwood, J. J.; Meikle, P. J. Correlation of acid alpha-glucosidase and glycogen content in skin fibroblasts with age of onset in Pompe disease. Clin. Chim. Acta 361: 191–198; 2005 doi:10.1016/j.cccn.2005.05.025.

    Article  PubMed  CAS  Google Scholar 

  • Van der Ploeg, A. T.; Kroos, M.; van Dongen, J. M.; Visser, W. J.; Bolhuis, P. A.; Loonen, M. C.; Reuser, A. J. Breakdown of lysosomal glycogen in cultured fibroblasts from glycogenosis type II patients after uptake of acid alpha-glucosidase. J. Neurol. Sci. 79: 327–336; 1987 doi:10.1016/0022-510X(87)90239-5.

    Article  PubMed  Google Scholar 

  • Van der Ploeg, A. T.; Winkel, L. P.; Van den Hout, J. M.; Kamphoven, J. H.; Disseldorp, J. A.; Remmerswaal, M.; Arts, W. F.; Loonen, M. C.; Vulto, A. G.; Van Doorn, P. A.; de Jong, G.; Hop, W.; Smit, G. P.; Shapira, S. K.; Boer, M. A.; Van Diggelen, O. P.; Reuser, A. J. Enzyme replacement therapy in late-onset Pompe’s disease: a three-year follow-up.. Ann. Neurol. 55: 495–502; 2004 doi:10.1002/ana.20019.

    Article  PubMed  CAS  Google Scholar 

  • Vincent-Lacaze, N.; Snyder, R. O.; Gluzman, R.; Bohl, D.; Lagarde, C.; Danos, O. Structure of adeno-associated virus vector DNA following transduction of the skeletal muscle. J. Virol 73: 1949–1955; 1999.

    PubMed  CAS  Google Scholar 

  • Wisselaar, H. A.; Kroos, M. A.; Hermans, M. M.; van Beeumen, J.; Reuser, A. J. Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J. Biol. Chem. 268: 2223–2231; 1993.

    PubMed  CAS  Google Scholar 

  • Xu, F.; Ding, E.; Migone, F.; Serra, D.; Schneider, A.; Chen, Y. T.; Amalfitano, A. Glycogen storage in multiple muscles of old GSD-II mice can be rapidly cleared after a single intravenous injection with a modified adenoviral vector expressing hGAA. J. Gene Med. 7: 171–178; 2005 doi:10.1002/jgm.660.

    Article  PubMed  CAS  Google Scholar 

  • Zaldumbide, A.; Hoeben, R. C. How not to be seen: immune-evasion strategies in gene therapy. Gene Ther. 15: 239–246; 2008 doi:10.1038/sj.gt.3303082.

    Article  PubMed  CAS  Google Scholar 

  • Zaretzky, J. Z.; Candotti, F.; Boerkoel, C.; Adams, E. M.; Yewdell, J. W.; Blaese, R. M.; Plotz, P. H. Retroviral transfer of acid alpha-glucosidase cDNA to enzyme-deficient myoblasts results in phenotypic spread of the genotypic correction by both secretion and fusion. Hum. Gene Ther. 8: 1555–1563; 1997 doi:10.1089/hum.1997.8.13-1555.

    Article  Google Scholar 

  • Ziegler, R. J.; Bercury, S. D.; Fidler, J.; Zhao, M. A.; Foley, J.; Taksir, T. V.; Ryan, S.; Hodges, B. L.; Scheule, R. K.; Shihabuddin, L. S.; Cheng, S. H. Ability of adeno-associated virus serotype 8-mediated hepatic expression of acid alpha-glucosidase to correct the biochemical and motor function deficits of presymptomatic and symptomatic Pompe mice. Hum. Gene Ther. 19: 609–721; 2008 doi:10.1089/hum.2008.010.

    Article  PubMed  CAS  Google Scholar 

  • Zufferey, R.; Donello, J. E.; Trono, D.; Hope, T. J. Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73: 2886–2892; 1999.

    PubMed  CAS  Google Scholar 

  • Zufferey, R.; Dull, T.; Mandel, R. J.; Bukovsky, A.; Quiroz, D.; Naldini, L.; Trono, D. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72: 9873–9880; 1998.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Charlotte Lahoutte and Dr. Sabrina Pichon (INSERM U567, Department of Genetics and Development) for their technical support in isolating satellite cells. We thank Dr. Alain Schmitt (Electron Microscopy Department, Institut Cochin) for his assistance in electron microscopy analysis. This work was supported by INSERM, the Association Vaincre les Maladies Lysosomales (VML), and the Association Française contre les Myopathies (AFM). E.R. was supported by a post-doctoral fellowship from VML and AFM. G.D.G. was supported by a doctoral fellowship from Genzyme and AFM.

Author information

Authors and Affiliations

  1. Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), INSERM U567, Paris, France

    Emmanuel Richard, Gaëlle Douillard-Guilloux, Lionel Batista & Catherine Caillaud

  2. Département Génétique et Développement, Faculté de Médecine Cochin Port-Royal, Institut Cochin, 24 rue du Faubourg St Jacques, 75014, Paris, France

    Catherine Caillaud

  3. INSERM U876, IFR 66, Université Bordeaux 2, Zone sud, bâtiment TP, 4ème étage, 146 rue Léo Saignat, 33076, Bordeaux, France

    Emmanuel Richard

Authors
  1. Emmanuel Richard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaëlle Douillard-Guilloux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lionel Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Catherine Caillaud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Emmanuel Richard or Catherine Caillaud.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richard, E., Douillard-Guilloux, G., Batista, L. et al. Correction of glycogenosis type 2 by muscle-specific lentiviral vector. In Vitro Cell.Dev.Biol.-Animal 44, 397–406 (2008). https://doi.org/10.1007/s11626-008-9138-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-008-9138-5

Keywords

Search

Navigation