Summary
Intravenous enzyme replacement therapy with recombinant human α-l-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg per week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg per week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing.
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Abbreviations
- ERT:
-
enzyme replacement therapy
- GAG:
-
glycosaminoglycan
- MPS:
-
mucopolysaccharidosis
- rhIDU:
-
recombinant human α-l-iduronidase
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Acknowledgements
Funding was provided by the Ryan Foundation for MPS Children and BioMarin Pharmaceutical Inc. Thanks to Michael McEntee, Rita Esquivel, and Dan Garner for their technical assistance. Thanks to Paul Fu, Sr, for measurement of urinary creatinine.
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Communicating editor: Ed Wraith
Competing interests: E.D.K. and T.L. are employees of BioMarin Pharmaceutical Inc., and have financial interest in laronidase (rhIDU). The study was funded by BioMarin Pharmaceutical Inc., and the Ryan Foundation for MPS Children. The sponsors did not influence the content of the work.
References to electronic databases: Laronidase: EC 3.2.1.76
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Passage, M.B., Krieger, A.W., Peinovich, M.C. et al. Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs. J Inherit Metab Dis 32 (Suppl 1), 253–258 (2009). https://doi.org/10.1007/s10545-009-1198-5
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DOI: https://doi.org/10.1007/s10545-009-1198-5