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

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• Mucopolysaccharidosis I (MPS I) is a rare genetic disorder caused by deficient α-L-iduronidase activity.
• Enzyme replacement therapy (ERT) with recombinant human α-L-iduronidase (rhIDU) is a standard treatment for MPS I.

Purpose of the Study:

• To compare the efficacy of continuous intravenous (IV) rhIDU administration versus the standard weekly IV infusion in MPS I dogs.
• To evaluate the impact of different rhIDU dosing strategies on enzyme levels and glycosaminoglycan (GAG) storage.

Main Methods:

• MPS I dogs received continuous IV rhIDU at 0.58 mg/kg/week or 2 mg/kg/week, or a standard weekly 3-hour infusion of 0.58 mg/kg.
• Plasma rhIDU concentrations, tissue iduronidase levels, and GAG storage were measured.
• Adverse events were monitored across all treatment groups.

Main Results:

• Peak plasma rhIDU concentrations were significantly higher with weekly infusions compared to continuous infusions.
• Continuous rhIDU administration resulted in lower tissue iduronidase levels and less GAG storage reduction, even at the higher dose.
• Adverse events were comparable across all treatment groups, indicating similar safety profiles.

Conclusions:

• Continuous IV rhIDU administration is less effective than weekly infusions for treating MPS I in dogs.
• The standard weekly 0.58 mg/kg rhIDU infusion is superior in achieving therapeutic enzyme levels and reducing GAG storage in MPS I models.