Dataset Information

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

ABSTRACT:

Objective

To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.

Study design

We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function.

Result

After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related.

Conclusion

rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.

SUBMITTER: Kishnani PS

PROVIDER: S-EPMC2692727 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

Kishnani Priya Sunil PS Nicolino Marc M Voit Thomas T Rogers R Curtis RC Tsai Anne Chun-Hui AC Waterson John J Herman Gail E GE Amalfitano Andreas A Thurberg Beth L BL Richards Susan S Davison Mark M Corzo Deyanira D Chen Y T YT

The Journal of pediatrics 20060701 1

<h4>Objective</h4>To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease.<h4>Study design</h4>We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of ...[more]

PMID: 16860134

Similar Datasets

Project description:Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid ?-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

Dataset Information

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

Objective

Study design

Result

Conclusion

Publications

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

Similar Datasets

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