Direct Comparison of Measures of Endurance, Mobility, and Joint Function During Enzyme-Replacement Therapy of Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): Results After 48 Weeks in a Phase 2 Open-Label Clinical Study of Recombinant Human <i>N</i>-Acetylgalactosamine 4-Sulfatase

Harmatz, Paul; Ketteridge, David; Giugliani, Roberto; Guffon, Natalie; Teles, Elisa Leão; Sá-Miranda, Clara; Yu, Zi‐Fan; Swiedler, Stuart J.; Hopwood, John J.

doi:10.1542/peds.2004-1023

Cited by 203 publications

(187 citation statements)

References 40 publications

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“…This rate of seroconversion is lower than has been reported for other forms of enzyme replacement therapy. 20,22,24,25,27,30 Interestingly, in the present study about one-third of the patients who developed antibodies were antibody-negative after 1 year of treatment, suggesting the development of immunological tolerance similar to what has been reported for enzyme replacement therapy in Gaucher disease 31 and Fabry disease. 32 The current treatment of MPS II has focused on managing symptoms, since no therapy is available.…”

Section: Discussionsupporting

confidence: 87%

“…24,25 In the MPS I double-blind, placebo-controlled phase III ERT study reported by Wraith and coworkers, 6 months of treatment with laronidase (recombinant ␣-L-iduronidase) significantly decreased urinary GAG, decreased liver and spleen volumes, improved %FVC (based on each patient's current height) by 4.3% (P ϭ 0.022) and increase the 6MWT distance by 38 m (P ϭ 0.066) compared to placebo. 22 In the MPS VI double-blind phase, placebo-controlled phase III ERT study, 6 months of treatment with galsulfase (recombinant human N-acetylgalactosamine 4-sulfatase) decreased urinary GAG and the distance walked in 12 minutes showed a longitudinal model-derived mean difference of 92 Ϯ 40 m (P ϭ 0.025) in favor of galsulfase.…”

Section: Discussionmentioning

confidence: 99%

“…Enzyme replacement therapy has been previously developed for MPS I 20,22 and MPS VI, 24,25 as well as for other lysosomal storage diseases. 26 -28 Both MPS I and MPS VI are caused by deficiencies in single enzymes involved in the catabolism of GAG, 1 and like MPS II, their phenotypic expression varies considerably.…”

Section: Discussionmentioning

confidence: 99%

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A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Muenzer

Wraith

Beck³

et al. 2006

Genetics in Medicine

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508

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Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II. Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg).Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline. Results: Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P ϭ 0.0049 for weekly and P ϭ 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P ϭ 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P ϭ 0.065), and a 160 mL increase in absolute forced vital capacity (P ϭ 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Muenzer

Wraith

Beck³

et al. 2006

Genetics in Medicine

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508

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“…We pooled cross-sectional and longitudinal height for age data from patients who participated in the MPS VI crosssectional Survey Study done in 2001-2002(Swiedler et al 2005; clinical trials and their extension programs, including phase 1/2, phase 2, phase 3 (Harmatz et al 2004;Harmatz et al 2005;Harmatz et al 2006;Harmatz et al 2008), and a phase 4 study ; the MPS VI clinical surveillance program (CSP; ClinicalTrials.gov: NCT00214773); and the Resurvey Study (Giugliani et al 2014) to construct growth charts for patients with the MPS VI disorder. Patients treated with galsulfase (recombinant human arylsulfatase B; rhASB; Naglazyme ® ; an enzyme replacement therapy [ERT] for MPS VI) or patients status post hematopoietic stem cell transplant (HSCT) were excluded from this analysis.…”

Section: Data Source For Integrated Height Analysismentioning

confidence: 99%

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

et al. 2014

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Background: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure.Objective: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease.Methods: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme ® , BioMarin Pharmaceutical Inc.), treatment naïve patients (n ¼ 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients 25 years of age with 513 height measurements were used for constructing reference growth curves.Results: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or 200 mg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) mg/mg creatinine for the patients 25 years of age with rapidly (n ¼ 131) and slowly (n ¼ 76) progressing MPS VI disease, respectively. The median growth curves for patients with and >200 mg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population.Conclusion: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients.

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“…This disparity was also observed in studies on other LSD mouse models, even when treated by prenatal or neonatal CNS gene delivery, such as MPS VII, 35 Krabbe, 36 Niemann-Pick 23 and Sandhoff, 19,37 as well as in ERT studies on LSDs regarding somatic tissues except liver. 7,[38][39][40] Previous studies showed that the secreted enzyme expressed from the hNaGlu cDNA was in the form of an 83 or 89 kDa precursor, while mature native hNaGlu is 77 kDa. 41,42 Further, the rNaGlu was poorly manose-6-phosphorylated, 41,42 and the majority of lysosomal enzymes are targeted to cells and lysosomes through mannose-6-phosphate (Man6-P) receptors.…”

Section: Increased Lifespan and Improved Behavioral Performances H Fumentioning

confidence: 99%

Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice

Jennings

et al. 2007

Gene Ther

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Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease, caused by the deficiency of a-N-acetylglucosaminidase (NaGlu), resulting in severe global neurological involvement with high mortality. One major hurdle in therapeutic development for MPS IIIB is the presence of the blood-brain barrier, which impedes the global central nervous system (CNS) delivery of therapeutic materials. In this study, we used a minimal invasive strategy, combining an intravenous (i.v.) and an intracisternal (i.c.) injection, following an i.v. infusion of mannitol, to complement the CNS delivery of adeno-associated viral (AAV) vector for treating MPS IIIB in young adult mice. This treatment resulted in a significantly prolonged lifespan of MPS IIIB mice (11.1-19.5 months), compared with that without treatment (7.9-11.3), and correlated with significantly improved behavioral performances, the restoration of functional NaGlu, and variable correction of lysosomal storage pathology in the CNS, as well as in different somatic tissues. This study demonstrated the great potential of combining i.v. and i.c. administration for improving rAAV CNS gene delivery and developing rAAV gene therapy for treating MPS IIIB in patients.

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Direct Comparison of Measures of Endurance, Mobility, and Joint Function During Enzyme-Replacement Therapy of Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): Results After 48 Weeks in a Phase 2 Open-Label Clinical Study of Recombinant Human N-Acetylgalactosamine 4-Sulfatase

Cited by 203 publications

References 40 publications

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)

Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice

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