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Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase).
Pediatrics. 2007 Jul; 120(1):e37-46.Ped

Abstract

OBJECTIVE

Our objective was to evaluate the safety, pharmacokinetics, and efficacy of laronidase in young, severely affected children with mucopolysaccharidosis I.

METHODS

This was a prospective, open-label, multinational study of 20 patients who had mucopolysaccharidosis I and were <5 years old (16 with Hurler syndrome, 4 with Hurler-Scheie syndrome) and were scheduled to receive intravenous laronidase at 100 U/kg (0.58 mg/kg) weekly for 52 weeks. Four patients underwent dosage increases to 200 U/kg for the last 26 weeks because of elevated urinary glycosaminoglycan levels at week 22.

RESULTS

Laronidase was well tolerated at both dosages. Investigators reported improved clinical status in 94% of patients at week 52. The mean urinary glycosaminoglycan level declined by approximately 50% at week 13 and was sustained thereafter. A more robust decrease in urinary glycosaminoglycan was observed in patients with low antibody levels and those who were receiving the 200 U/kg dosage. On examination, the liver edge was reduced by 69.5% in patients with a palpable liver at baseline and week 52 (n = 10). The proportion of patients with left ventricular hypertrophy decreased from 53% to 17%. Global assessment of sleep studies showed improvement or stabilization in 67% of patients, and the apnea/hypopnea index decreased by 5.8 events per hour (-8.5%) in those with abnormal baseline values. The younger patients with Hurler syndrome (<2.5 years) and all 4 patients with Hurler-Scheie syndrome showed normal mental development trajectories during the 1-year treatment period.

CONCLUSIONS

Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are <5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation.

Authors+Show Affiliations

Royal Manchester Children's Hospital, Willink Biochemical Genetics Unit, Hospital Road, Pendlebury, Manchester M27 1HA, United Kingdom. ed.wraith@cmmc.nhs.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17606547

Citation

Wraith, J Edmond, et al. "Enzyme Replacement Therapy in Patients Who Have Mucopolysaccharidosis I and Are Younger Than 5 Years: Results of a Multinational Study of Recombinant Human alpha-L-iduronidase (laronidase)." Pediatrics, vol. 120, no. 1, 2007, pp. e37-46.
Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics. 2007;120(1):e37-46.
Wraith, J. E., Beck, M., Lane, R., van der Ploeg, A., Shapiro, E., Xue, Y., Kakkis, E. D., & Guffon, N. (2007). Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics, 120(1), e37-46.
Wraith JE, et al. Enzyme Replacement Therapy in Patients Who Have Mucopolysaccharidosis I and Are Younger Than 5 Years: Results of a Multinational Study of Recombinant Human alpha-L-iduronidase (laronidase). Pediatrics. 2007;120(1):e37-46. PubMed PMID: 17606547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). AU - Wraith,J Edmond, AU - Beck,Michael, AU - Lane,Roderick, AU - van der Ploeg,Ans, AU - Shapiro,Elsa, AU - Xue,Yong, AU - Kakkis,Emil D, AU - Guffon,Nathalie, Y1 - 2007/06/04/ PY - 2007/7/4/pubmed PY - 2007/8/4/medline PY - 2007/7/4/entrez SP - e37 EP - 46 JF - Pediatrics JO - Pediatrics VL - 120 IS - 1 N2 - OBJECTIVE: Our objective was to evaluate the safety, pharmacokinetics, and efficacy of laronidase in young, severely affected children with mucopolysaccharidosis I. METHODS: This was a prospective, open-label, multinational study of 20 patients who had mucopolysaccharidosis I and were <5 years old (16 with Hurler syndrome, 4 with Hurler-Scheie syndrome) and were scheduled to receive intravenous laronidase at 100 U/kg (0.58 mg/kg) weekly for 52 weeks. Four patients underwent dosage increases to 200 U/kg for the last 26 weeks because of elevated urinary glycosaminoglycan levels at week 22. RESULTS: Laronidase was well tolerated at both dosages. Investigators reported improved clinical status in 94% of patients at week 52. The mean urinary glycosaminoglycan level declined by approximately 50% at week 13 and was sustained thereafter. A more robust decrease in urinary glycosaminoglycan was observed in patients with low antibody levels and those who were receiving the 200 U/kg dosage. On examination, the liver edge was reduced by 69.5% in patients with a palpable liver at baseline and week 52 (n = 10). The proportion of patients with left ventricular hypertrophy decreased from 53% to 17%. Global assessment of sleep studies showed improvement or stabilization in 67% of patients, and the apnea/hypopnea index decreased by 5.8 events per hour (-8.5%) in those with abnormal baseline values. The younger patients with Hurler syndrome (<2.5 years) and all 4 patients with Hurler-Scheie syndrome showed normal mental development trajectories during the 1-year treatment period. CONCLUSIONS: Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are <5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation. SN - 1098-4275 UR - https://www.unboundmedicine.com/medline/citation/17606547/Enzyme_replacement_therapy_in_patients_who_have_mucopolysaccharidosis_I_and_are_younger_than_5_years:_results_of_a_multinational_study_of_recombinant_human_alpha_L_iduronidase__laronidase__ L2 - http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&amp;pmid=17606547 DB - PRIME DP - Unbound Medicine ER -