Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy
Date
2013
Authors
Braunlin, E.
Rosenfeld, H.
Kampmann, C.
Johnson, J.
Beck, M.
Giugliani, R.
Guffon, N.
Ketteridge, D.
Miranda, C.
Scarpa, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Inherited Metabolic Disease, 2013; 36(2):385-394
Statement of Responsibility
E. Braunlin, H. Rosenfeld, C. Kampmann, J. Johnson, M. Beck, R. Giugliani, N. Guffon, D. Ketteridge, C. M. Sá Miranda, M. Scarpa, I. V. Schwartz, E. Leão Teles, J. E. Wraith, P. Barrios, E. Dias da Silva, G. Kurio, M. Richardson, G. Gildengorin, J. J. Hopwood, M. Imperiale, A. Schatz, C. Decker, P. Harmatz, MPS VI Study Group
Conference Name
Abstract
Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme®). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those ≥12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6–1.9 SD greater than normal, was present for ages both <12 and ≥12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those ≥12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© The Author(s) 2012. This article is published with open access at Springerlink.com