Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17352
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Harmatz, P. | - |
dc.contributor.author | Ketteridge, D. | - |
dc.contributor.author | Giugliani, R. | - |
dc.contributor.author | Guffon, N. | - |
dc.contributor.author | Teles, E. | - |
dc.contributor.author | Miranda, C. | - |
dc.contributor.author | Yu, Z. | - |
dc.contributor.author | Swiedler, S. | - |
dc.contributor.author | Hopwood, J. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Pediatrics, 2005; 115(6):E681-E689 | - |
dc.identifier.issn | 0031-4005 | - |
dc.identifier.issn | 0031-4005 | - |
dc.identifier.uri | http://hdl.handle.net/2440/17352 | - |
dc.description.abstract | <h4>Objective</h4>Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (ASB). This enzyme deficiency leads to a progressive disorder with multiple tissue and organ involvement. The disease is rare and is heterogeneous in its clinical presentation and progression. A potential treatment for this disease exists in the form of enzyme-replacement therapy (ERT) with recombinant human ASB (rhASB), and a phase 1/2 randomized, double-blind, 2-dose (0.2 and 1 mg/kg) study in 6 patients showed the treatment at 48 weeks to be well tolerated. Greater biochemical efficacy based on a urine glycosaminoglycan occurred in the high-dose (1 mg/kg) group, and functional improvement seemed greater in patients in the high-dose group with rapidly advancing disease. On the basis of the phase 1/2 results, a phase 2, open-label study in patients with rapidly advancing disease was initiated primarily to evaluate efficacy variables that measure endurance, mobility, and joint function in a larger group of patients.<h4>Methods</h4>This was an open-label, multinational study of 10 MPS VI patients who received 48 weekly intravenous treatments with 1.0 mg/kg rhASB and had assessments of biochemical and clinical responses at regular intervals.<h4>Results</h4>After 24 weeks of treatment, each patient on average experienced a 155-m (98%) improvement in the 12-minute walk, a 64-m (62%) improvement at the 6-minute time point of the 12-minute walk, and a 48-stair (110%) gain in the 3-minute stair climb versus the baseline mean values. Additional improvements after 48 weeks of treatment were observed, including mean values of 211 m (138%) in the 12-minute walk, 75 m (80%) at the 6-minute time point of the 12-minute walk, and 61-stair (147%) gain in the 3-minute stair climb versus the baseline mean values. Joint Pain and Stiffness Questionnaire scores improved by at least 50% by week 24 and were maintained at week 48, whereas there were only small improvements in active shoulder range of motion (<10 degrees ) and in the time taken to stand, walk, and turn starting from a seated position (Expanded Timed Get-Up and Go test). Improvement in pulmonary function based on forced vital capacity and forced expiratory volume at 1 minute in the absence of growth was observed in 3 of 6 patients, and the observed gains occurred in the 24- to 48-week treatment interval. A mean decrease of 76% in urinary excretion of glycosaminoglycans indicated that a satisfactory biochemical response was achieved and the ERT was well tolerated.<h4>Conclusions</h4>The results suggest that a 12-minute walk extends the dynamic range of the conventional 6-minute walk and, along with the 3-minute stair climb, provide a robust approach to documenting the improvement in endurance in MPS VI patients who undergo ERT with rhASB. | - |
dc.description.statementofresponsibility | Harmatz, Paul ; Ketteridge, David ; Giugliani, Roberto ; Guffon, Natalie ; Teles, Elisa Leão ; Miranda, M Clara Sá ; Yu, Zi-fan ; Swiedler, Stuart J ; Hopwood, John J for the MPS VI Study Group | - |
dc.language.iso | en | - |
dc.publisher | Amer Acad Pediatrics | - |
dc.source.uri | http://dx.doi.org/10.1542/peds.2004-1023 | - |
dc.subject | MPS VI Study Group | - |
dc.subject | Joints | - |
dc.subject | Humans | - |
dc.subject | Mucopolysaccharidosis VI | - |
dc.subject | N-Acetylgalactosamine-4-Sulfatase | - |
dc.subject | Glycosaminoglycans | - |
dc.subject | Recombinant Fusion Proteins | - |
dc.subject | Isoantibodies | - |
dc.subject | Hand Strength | - |
dc.subject | Range of Motion, Articular | - |
dc.subject | Treatment Outcome | - |
dc.subject | Walking | - |
dc.subject | Injections, Intravenous | - |
dc.subject | Severity of Illness Index | - |
dc.subject | Recovery of Function | - |
dc.subject | Antibody-Dependent Cell Cytotoxicity | - |
dc.subject | Physical Endurance | - |
dc.subject | Movement | - |
dc.subject | Adolescent | - |
dc.subject | Adult | - |
dc.subject | Child | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.title | 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 | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1542/peds.2004-1023 | - |
pubs.publication-status | Published | - |
Appears in Collections: | Aurora harvest 6 Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.