Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation

Lynda E. Polgreen, Troy C Lund, Elizabeth A Braunlin, Jakub Tolar, Bradley S Miller, Ellen Fung, Chester B Whitley, Julie Eisengart, Elise Northrop, Kyle Rudser, Weston P. Miller, Paul J Orchard

Research output: Contribution to journalArticle

Abstract

Background: Mucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT. Methods: This 2-year open-label pilot study of laronidase included ten patients (age 5–13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls. Results: The two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients. Conclusions: Laronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made.

Original languageEnglish (US)
JournalPediatric Research
DOIs
StateAccepted/In press - Jan 1 2019

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Mucopolysaccharidosis I
Cell Transplantation
Clinical Trials
Anti-Idiotypic Antibodies
Pharmaceutical Preparations
Lysosomal Storage Diseases
Growth
Tissue Donors
Walk Test

Cite this

@article{63c3643b4dc54c7d8217bcc04e973f5d,
title = "Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation",
abstract = "Background: Mucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT. Methods: This 2-year open-label pilot study of laronidase included ten patients (age 5–13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls. Results: The two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients. Conclusions: Laronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made.",
author = "Polgreen, {Lynda E.} and Lund, {Troy C} and Braunlin, {Elizabeth A} and Jakub Tolar and Miller, {Bradley S} and Ellen Fung and Whitley, {Chester B} and Julie Eisengart and Elise Northrop and Kyle Rudser and Miller, {Weston P.} and Orchard, {Paul J}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41390-019-0541-2",
language = "English (US)",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation

AU - Polgreen, Lynda E.

AU - Lund, Troy C

AU - Braunlin, Elizabeth A

AU - Tolar, Jakub

AU - Miller, Bradley S

AU - Fung, Ellen

AU - Whitley, Chester B

AU - Eisengart, Julie

AU - Northrop, Elise

AU - Rudser, Kyle

AU - Miller, Weston P.

AU - Orchard, Paul J

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Mucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT. Methods: This 2-year open-label pilot study of laronidase included ten patients (age 5–13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls. Results: The two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients. Conclusions: Laronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made.

AB - Background: Mucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT. Methods: This 2-year open-label pilot study of laronidase included ten patients (age 5–13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls. Results: The two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients. Conclusions: Laronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made.

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