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Enzyme-replacement therapy in mucopolysaccharidosis I
E D Kakkis1, J Muenzer, G E Tiller
1Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, Calif, USA. ekakkis@biomarinpharm.com
The New England Journal of Medicine
|February 15, 2001
Summary
Enzyme-replacement therapy using recombinant human alpha-L-iduronidase effectively treated mucopolysaccharidosis I by reducing lysosomal storage and improving clinical symptoms in patients. This therapy showed significant benefits in growth, organ size, and functional capacity.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Mucopolysaccharidosis I (MPS I) is a rare genetic disorder caused by deficient alpha-L-iduronidase enzyme activity.
- Lysosomal storage diseases like MPS I lead to progressive cellular damage and multi-systemic complications.
Purpose of the Study:
- To evaluate the efficacy of enzyme-replacement therapy (ERT) using recombinant human alpha-L-iduronidase in patients with MPS I.
- To assess the impact of ERT on clinical manifestations and biochemical markers of MPS I.
Main Methods:
- Ten patients diagnosed with MPS I (aged 5-22 years) received intravenous recombinant human alpha-L-iduronidase (125,000 U/kg) weekly for 52 weeks.
- Comprehensive evaluations included clinical exams, MRI, echocardiography, range-of-motion, polysomnography, laboratory tests, and urinary glycosaminoglycan (GAG) excretion measurements.
Main Results:
- Significant reduction in hepatosplenomegaly observed; liver size normalized in 80% of patients by 26 weeks.
- Prepubertal patients showed increased growth rates (height 85%, weight 131%) and improved range of motion.
- Apnea-hypopnea episodes decreased by 61%, cardiac function improved, and urinary GAG excretion reduced by 63%.
Conclusions:
- Recombinant human alpha-L-iduronidase ERT effectively reduces lysosomal storage in MPS I patients.
- The therapy ameliorates key clinical manifestations, including organomegaly, growth deficits, and respiratory compromise.
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