Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs

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...

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Bibliographic Details
Published in:	Journal of inherited metabolic disease Vol. 32; no. Suppl 1; pp. 253 - 258
Main Authors:	Passage, M. B., Krieger, A. W., Peinovich, M. C., Lester, T., Le, S. Q., Dickson, P. I., Kakkis, E. D.
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-12-2009 Blackwell Publishing Ltd
Subjects:	Animals Biochemistry Disease Models, Animal Dogs Enzyme Replacement Therapy - instrumentation Enzyme Replacement Therapy - methods Glycosaminoglycans - metabolism Human Genetics Humans Iduronidase - administration & dosage Iduronidase - blood Infusion Pumps Infusions, Intravenous Internal Medicine Medicine Medicine & Public Health Metabolic Diseases Mucopolysaccharidosis I - drug therapy Mucopolysaccharidosis I - metabolism Pediatrics Recombinant Proteins - administration & dosage Short Report Treatment Outcome Fabry Disease Enzyme Replacement Therapy Weekly Dose Disease Gauche Continuous Infusion
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Summary:	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.
Bibliography:	References to electronic databases 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. Laronidase: EC 3.2.1.76 Communicating editor: Ed Wraith ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 Thomas Lester – Performed infusions and ELISA for anti-iduronidase antibodies Patricia Dickson serves as guarantor for the article, accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Patricia I. Dickson – Analyzed and interpreted data and prepared the manuscript Emil D. Kakkis – Conceptualized and oversaw the experiment Merry B. Passage – performed the infusions, biochemical analyses, prepared the manuscript and oversaw the implementation of the experiment Steven Q. Le – Performed biochemical analyses Maryn C. Peinovich – Performed ELISA for anti-iduronidase antibodies and assisted with animal infusions Aimee W. Krieger – Performed infusions and collected data
ISSN:	0141-8955 1573-2665
DOI:	10.1007/s10545-009-1198-5