Enzyme replacement therapy for mucopolysaccharidosis VI: Long-term cardiac effects of galsulfase (Naglazyme®) therapy

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. ImperialeA. Schatz, C. Decker, P. Harmatz

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57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)385-394
Number of pages10
JournalJournal of Inherited Metabolic Disease
Issue number2
StatePublished - Mar 2013

Bibliographical note

Funding Information:
Acknowledgments We acknowledge the participation of study patients and their families and the expert assistance of all study site coordinators and study site personnel. This study was an investigator-initiated study sponsored by BioMarin Pharmaceutical Inc., and supported, in part, with funds provided by the National Center for Research Resources, 5 M01 RR-01271 (Dr. Harmatz), 5 M01 RR-00400 (Dr. Whitley), M01 RR-00334 (Dr. Steiner), and UL1-RR-024134 (Dr. Kaplan). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The support of the European Consortium for Lysosomal Diseases (EUCLYD, 7th Frame-work program, European Union) is acknowledged (Dr. Beck).

Funding Information:
Conflict of interest Drs. Harmatz, Beck, and Giugliani have provided consulting support to BioMarin Pharmaceutical Inc., Novato, CA. Drs. Harmatz, Beck, Scarpa, and Braunlin reported receiving a speaker’s honorarium and travel support from BioMarin. Drs. Harmatz and Scarpa have received research grants from BioMarin. BioMarin is a supporter of the Lysosomal Disease Network’s WORLD Symposium organized by Dr. Whitley. Drs. Decker and Imperiale are employees of BioMarin Pharmaceutical Inc.; both are stockholders. Andrea Schatz is an employee of BioMarin.


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