Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17352
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
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 |
Author: | Harmatz, P. Ketteridge, D. Giugliani, R. Guffon, N. Teles, E. Miranda, C. Yu, Z. Swiedler, S. Hopwood, J. |
Citation: | Pediatrics, 2005; 115(6):E681-E689 |
Publisher: | Amer Acad Pediatrics |
Issue Date: | 2005 |
ISSN: | 0031-4005 0031-4005 |
Statement of Responsibility: | 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 |
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. |
Keywords: | MPS VI Study Group Joints Humans Mucopolysaccharidosis VI N-Acetylgalactosamine-4-Sulfatase Glycosaminoglycans Recombinant Fusion Proteins Isoantibodies Hand Strength Range of Motion, Articular Treatment Outcome Walking Injections, Intravenous Severity of Illness Index Recovery of Function Antibody-Dependent Cell Cytotoxicity Physical Endurance Movement Adolescent Adult Child Female Male |
DOI: | 10.1542/peds.2004-1023 |
Published version: | http://dx.doi.org/10.1542/peds.2004-1023 |
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.