Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs.
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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Los Angeles Biomedical Research Institute at Harbor, UCLA, 1124 W. Carson Street, E-4, Torrance, CA 90502, USA.
Krieger
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Peinovich
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MC
Lester
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Le
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Dickson
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Kakkis
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D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D056947:Enzyme Replacement Therapy / Q000295:instrumentation / Q000379:methods*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage* / Q000097:blood; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome
D006025:Glycosaminoglycans; D011994:Recombinant Proteins; D007068:Iduronidase