Journal Article

Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

Wraith, J. Edmond, Scarpa, Maurizio, Teles, Elisa Leão, Schwartz, Ida Vanessa D, Hopwood, John J, Whitley, Chester B, Kaplan, Paige, Miranda, M. Clara Sá, Swiedler, Stuart J, Berger, Kenneth I, Giugliani, Roberto, Beck, Michael, Guffon, Nathalie, Steiner, Robert, Decker, Celeste, Arash, Laila, Plecko, Barbara, Hardy, Karen, Harmatz, Paul, Yu, Zi-Fan, Ketteridge, David

2010

نظرة عامة

Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients.

• الناشر: Dordrecht : Springer Netherlands,Springer Netherlands,Springer,Blackwell Publishing Ltd
• موضوع: Adolescent / Adult / Biochemistry / Biological and medical sciences / Carbohydrates (enzymatic deficiencies). Glycogenosis / Child / Child, Preschool / Cross-Sectional Studies / Double-Blind Method / Errors of metabolism / Human Genetics / Humans / Internal Medicine / Longitudinal Studies / Lung - drug effects / Lung - physiology / Lung - physiopathology / Medical genetics / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Mucopolysaccharidosis VI - blood / Mucopolysaccharidosis VI - physiopathology / Mucopolysaccharidosis VI - therapy / N-Acetylgalactosamine-4-Sulfatase - therapeutic use / Original / Original Article / Pediatrics / Placebos / Recombinant Proteins - metabolism / Research Design / Respiratory Function Tests