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Journal of Neurology

, 257:91 | Cite as

Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial

  • S. Strothotte
  • N. Strigl-Pill
  • B. Grunert
  • C. Kornblum
  • K. Eger
  • C. Wessig
  • M. Deschauer
  • F. Breunig
  • F. X. Glocker
  • S. Vielhaber
  • A. Brejova
  • M. Hilz
  • K. Reiners
  • W. Müller-Felber
  • E. Mengel
  • M. Spranger
  • Benedikt Schoser
Original Communication

Abstract

Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid α-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers’ maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers’ test, the CK levels and the 6-min walk test (341 ± 149.49 m, median 342.25 m at baseline; 393 ± 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

Keywords

Enzyme replacement therapy Glycogen storage disease type 2 Pompe disease Alglucosidase alfa 

Notes

Acknowledgment

We thank the patients and their families for their patience and long-term cooperation. We also thank the technical team at the involved treatment centers. We thank Dr. Dieter Gläser for performing genetic analyses in some of our patients and Prof. Klaus V. Toyka for helpful comments.

References

  1. 1.
    Van der Ploeg AT, Reuser AJJ (2008) Lysosomal storage disease 2–Pompe′s disease. Lancet 372:1342–1352CrossRefPubMedGoogle Scholar
  2. 2.
    Case LE, Koeberl DD, Young SP, Bali D, De Armey SM, Mackey J, Kishnani PS (2008) Improvement with ongoing enzyme replacement therapy in advanced late-onset Pompe disease: a case study. Mol Genet Metab 95:233–235CrossRefPubMedGoogle Scholar
  3. 3.
    Ghosh P, Dahms NM, Kornfeld S (2003) Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 4:202–212CrossRefPubMedGoogle Scholar
  4. 4.
    Joshi PR, Glaeser D, Schmidt S, Vorgerd M, Winterholler M, Eger K, Zierz S, Deschauer M Molecular genetic characterization of German patients with late-onset glycogen storage disease type II. J Inherit Metab Dis, PMID: 18607768 (in press)Google Scholar
  5. 5.
    Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D (2006) A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 148:671–676CrossRefPubMedGoogle Scholar
  6. 6.
    Kornfeld S (1992) Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem 61:307–330CrossRefPubMedGoogle Scholar
  7. 7.
    Martiniuk F, Chen A, Mack A, Arvanitopoulos E, Chen Y, Rom WN et al (1998) Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet 79:69–72CrossRefPubMedGoogle Scholar
  8. 8.
    Moreland RJ, Jin X, Zhang XK, Decker RW, Albee KL, Lee KL et al (2005) Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J Biol Chem 280:6780–6791CrossRefPubMedGoogle Scholar
  9. 9.
    Müller-Felber W, Horvath R, Gempel K, Podskarbi T, Shin YS, Pongratz D, Walter MC, Baethmann M, Schlotter-Weigel B, Lochmüller H, Schoser BGH (2007) Late-onset Pompe disease: clinical and neurophysiological spectrum of 38 patients with a long-term follow-up in 18 patients. Neuromuscul Disord 17:698–706CrossRefPubMedGoogle Scholar
  10. 10.
    Pompe JC (1932) Over idiopathische hypertrofie van het hart. Ned Tijdsch Geneesk 76:304–311Google Scholar
  11. 11.
    Rossi M, Parenti G, Della CR, Romano A, Mansi G, Agovino T et al (2007) Long-term enzyme replacement therapy for Pompe disease with recombinant human alphaglucosidase derived from Chinese hamster ovary cells. J Child Neurol 22:565–573CrossRefPubMedGoogle Scholar
  12. 12.
    Schoser BGH, Müller-Höcker J, Gempel K, Horvath R, Pongratz D, Lochmüller H, Muller-Felber W (2007) Glycogen storage disease type 2: clinic-pathological phenotype revisited. Neuropathol Appl Neurol 33:544–559Google Scholar
  13. 13.
    Schoser B, Hill V, Raben N (2008) Therapeutic approaches in glycogen storage disease type II (GSDII)/Pompe disease. Neurotherapeutics 5:569–578CrossRefPubMedGoogle Scholar
  14. 14.
    Van der Beek NAME, Hagemans MLC, Reuser AJJ, Hop WCJ, Van der Ploeg AT, Van Doorn PA, Wokke JHJ (2009) Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease. Neuromuscul Disord 19:113–117CrossRefPubMedGoogle Scholar
  15. 15.
    Winkel LP, Van den Hout JM, Kamphoven JH, Disseldorp JA, Remmerswaal M, Arts WF et al (2004) Enzyme replacement therapy in late-onset Pompe’s disease: a three-year follow-up. Ann Neurol 55:495–502CrossRefPubMedGoogle Scholar
  16. 16.
    Winkel LP, Hagemans ML, Van Doorn PA, Loonen MC, Hop WJ, Reuser AJ et al (2005) The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 252:875–884CrossRefPubMedGoogle Scholar
  17. 17.
    Wisselaar HA, Kroos MA, Hermans MM, van Beeumen J, Reuser AJ (1993) Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J Biol Chem 268:2223–2231PubMedGoogle Scholar
  18. 18.
    Wokke JHJ, Escolar DM, Pestronk A, Jaffe KM, Carter GY, van den Berg LH, Florence JM, Mayhew J, Skrinar A, Corzo D, Laforet P (2008) Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve 35:1236–1245CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • S. Strothotte
    • 1
  • N. Strigl-Pill
    • 1
  • B. Grunert
    • 2
  • C. Kornblum
    • 3
  • K. Eger
    • 4
  • C. Wessig
    • 5
  • M. Deschauer
    • 4
  • F. Breunig
    • 6
  • F. X. Glocker
    • 7
  • S. Vielhaber
    • 8
  • A. Brejova
    • 8
  • M. Hilz
    • 9
  • K. Reiners
    • 5
  • W. Müller-Felber
    • 10
  • E. Mengel
    • 11
  • M. Spranger
    • 2
  • Benedikt Schoser
    • 1
  1. 1.Department of Neurology, Friedrich Baur InstituteLudwig Maximilian University MunichMunichGermany
  2. 2.Neurologisches Rehabilitationszentrum FriedehorstBremenGermany
  3. 3.Department of NeurologyUniversity Hospital of BonnBonnGermany
  4. 4.Department of NeurologyMartin Luther University Halle-WittenbergHalleGermany
  5. 5.Department of NeurologyJulius Maximilian University WürzburgWürzburgGermany
  6. 6.Department of NephrologyJulius Maximilian University WürzburgWürzburgGermany
  7. 7.Department of NeurologyUniversity Hospital FreiburgFreiburgGermany
  8. 8.Department of NeurologyUniversity Hospital MagdeburgMagdeburgGermany
  9. 9.Department of NeurologyUniversity ErlangenErlangenGermany
  10. 10.Department of NeuropediatricsLudwig Maximilian University MunichMunichGermany
  11. 11.Department of PaediatricsJohannes Gutenberg University MainzMainzGermany

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