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Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II.
J Inherit Metab Dis. 2010 Dec; 33(6):727-35.JI

Abstract

OBJECTIVES

Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.

METHODS

Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO(2)), and muscle enzymes were assessed every 6 months.

RESULTS

The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS >3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO(2) decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT.

CONCLUSIONS

Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.

Authors+Show Affiliations

Regional Coordination Centre for Rare Diseases, University Hospital Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. bembi.bruno@aoud.sanita.fvg.itNo 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
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20838899

Citation

Bembi, Bruno, et al. "Long-term Observational, Non-randomized Study of Enzyme Replacement Therapy in Late-onset Glycogenosis Type II." Journal of Inherited Metabolic Disease, vol. 33, no. 6, 2010, pp. 727-35.
Bembi B, Pisa FE, Confalonieri M, et al. Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. J Inherit Metab Dis. 2010;33(6):727-35.
Bembi, B., Pisa, F. E., Confalonieri, M., Ciana, G., Fiumara, A., Parini, R., Rigoldi, M., Moglia, A., Costa, A., Carlucci, A., Danesino, C., Pittis, M. G., Dardis, A., & Ravaglia, S. (2010). Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. Journal of Inherited Metabolic Disease, 33(6), 727-35. https://doi.org/10.1007/s10545-010-9201-8
Bembi B, et al. Long-term Observational, Non-randomized Study of Enzyme Replacement Therapy in Late-onset Glycogenosis Type II. J Inherit Metab Dis. 2010;33(6):727-35. PubMed PMID: 20838899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. AU - Bembi,Bruno, AU - Pisa,Federica Edith, AU - Confalonieri,Marco, AU - Ciana,Giovanni, AU - Fiumara,Agata, AU - Parini,Rossella, AU - Rigoldi,Miriam, AU - Moglia,Arrigo, AU - Costa,Alfredo, AU - Carlucci,Annalisa, AU - Danesino,Cesare, AU - Pittis,Maria Gabriela, AU - Dardis,Andrea, AU - Ravaglia,Sabrina, Y1 - 2010/09/14/ PY - 2010/06/16/received PY - 2010/08/24/accepted PY - 2010/08/11/revised PY - 2010/9/15/entrez PY - 2010/9/15/pubmed PY - 2011/3/16/medline SP - 727 EP - 35 JF - Journal of inherited metabolic disease JO - J. Inherit. Metab. Dis. VL - 33 IS - 6 N2 - OBJECTIVES: Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII. METHODS: Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO(2)), and muscle enzymes were assessed every 6 months. RESULTS: The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS >3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO(2) decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT. CONCLUSIONS: Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/20838899/Long_term_observational_non_randomized_study_of_enzyme_replacement_therapy_in_late_onset_glycogenosis_type_II_ L2 - https://doi.org/10.1007/s10545-010-9201-8 DB - PRIME DP - Unbound Medicine ER -