Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial

Andrea Amalfitano, A. Resai Bengur, Richard P. Morse, Joseph M. Majure, Laura E. Case, Deborah L. Veerling, Joanne Mackey, Priya Kishnani, Wendy Smith, Alison McVie-Wylie, Jennifer A. Sullivan, George E. Hoganson, John A. Phillips, G. Bradley Schaefer, Joel Charrow, Russell E. Ware, Edward H. Bossen, Yuan Tsong Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

359 Scopus citations


Purpose: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid α-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. Methods: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. Results: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. Conclusions: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Original languageEnglish (US)
Pages (from-to)132-138
Number of pages7
JournalGenetics in Medicine
Issue number2
StatePublished - 2001


  • Enzyme replacement therapy
  • Glycogen storage disease type II
  • Pompe disease

ASJC Scopus subject areas

  • Genetics(clinical)


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