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Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.
Genet Med 2001 Mar-Apr; 3(2):132-8GM

Abstract

PURPOSE

Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-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.

Authors+Show Affiliations

Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11286229

Citation

Amalfitano, A, et al. "Recombinant Human Acid Alpha-glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial." Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 3, no. 2, 2001, pp. 132-8.
Amalfitano A, Bengur AR, Morse RP, et al. Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med. 2001;3(2):132-8.
Amalfitano, A., Bengur, A. R., Morse, R. P., Majure, J. M., Case, L. E., Veerling, D. L., ... Chen, Y. T. (2001). Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 3(2), pp. 132-8.
Amalfitano A, et al. Recombinant Human Acid Alpha-glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial. Genet Med. 2001;3(2):132-8. PubMed PMID: 11286229.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. AU - Amalfitano,A, AU - Bengur,A R, AU - Morse,R P, AU - Majure,J M, AU - Case,L E, AU - Veerling,D L, AU - Mackey,J, AU - Kishnani,P, AU - Smith,W, AU - McVie-Wylie,A, AU - Sullivan,J A, AU - Hoganson,G E, AU - Phillips,J A,3rd AU - Schaefer,G B, AU - Charrow,J, AU - Ware,R E, AU - Bossen,E H, AU - Chen,Y T, PY - 2001/4/5/pubmed PY - 2001/8/15/medline PY - 2001/4/5/entrez SP - 132 EP - 8 JF - Genetics in medicine : official journal of the American College of Medical Genetics JO - Genet. Med. VL - 3 IS - 2 N2 - PURPOSE: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-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. SN - 1098-3600 UR - https://www.unboundmedicine.com/medline/citation/11286229/Recombinant_human_acid_alpha_glucosidase_enzyme_therapy_for_infantile_glycogen_storage_disease_type_II:_results_of_a_phase_I/II_clinical_trial_ L2 - http://dx.doi.org/10.109700125817-200103000-00007 DB - PRIME DP - Unbound Medicine ER -