Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation

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

doi:10.1038/s41390-019-0541-2

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation

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

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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 language	English (US)
Pages (from-to)	104-111
Number of pages	8
Journal	Pediatric Research
Volume	87
Issue number	1
DOIs	https://doi.org/10.1038/s41390-019-0541-2
State	Published - Jan 1 2020

Bibliographical note

Funding Information:
We gratefully acknowledge the study participants and parents as well as the study coordinators Nicole Sando and Jennifer Danielson who made this project possible. All phases of this study were supported by a research grant from Sanofi/Genzyme to P.J. O.. The natural history data was supported by grant numbers K23AR057789 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to L.E.P., U54NS065768 from the National Institute of Neurological Disorders and Stroke to L.E. P. (PI: C.B.W.), and by UL1TR001881, UL1TR000114 and UL1RR024131 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) to UCLA/LA BioMed, to the University of Minnesota, and to the Children’s Hospital Research Center, Oakland, Clinical and Translational Science Institutes (CTSI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CTSI or the NIH.

Publisher Copyright:
© 2019, The Author(s).

PubMed: MeSH publication types

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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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 Elizabeth Braunlin and Jakub Tolar and Miller, {Bradley S.} and Ellen Fung and Whitley, {Chester B.} and Eisengart, {Julie B.} and Elise Northrop and Kyle Rudser and Miller, {Weston P.} and Orchard, {Paul J.}",

note = "Funding Information: We gratefully acknowledge the study participants and parents as well as the study coordinators Nicole Sando and Jennifer Danielson who made this project possible. All phases of this study were supported by a research grant from Sanofi/Genzyme to P.J. O.. The natural history data was supported by grant numbers K23AR057789 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to L.E.P., U54NS065768 from the National Institute of Neurological Disorders and Stroke to L.E. P. (PI: C.B.W.), and by UL1TR001881, UL1TR000114 and UL1RR024131 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) to UCLA/LA BioMed, to the University of Minnesota, and to the Children{\textquoteright}s Hospital Research Center, Oakland, Clinical and Translational Science Institutes (CTSI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CTSI or the NIH. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2020",

month = jan,

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doi = "10.1038/s41390-019-0541-2",

language = "English (US)",

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pages = "104--111",

journal = "Pediatric Research",

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

AU - Polgreen, Lynda E.

AU - Lund, Troy C.

AU - Braunlin, Elizabeth

AU - Tolar, Jakub

AU - Miller, Bradley S.

AU - Fung, Ellen

AU - Whitley, Chester B.

AU - Eisengart, Julie B.

AU - Northrop, Elise

AU - Rudser, Kyle

AU - Miller, Weston P.

AU - Orchard, Paul J.

N1 - Funding Information: We gratefully acknowledge the study participants and parents as well as the study coordinators Nicole Sando and Jennifer Danielson who made this project possible. All phases of this study were supported by a research grant from Sanofi/Genzyme to P.J. O.. The natural history data was supported by grant numbers K23AR057789 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to L.E.P., U54NS065768 from the National Institute of Neurological Disorders and Stroke to L.E. P. (PI: C.B.W.), and by UL1TR001881, UL1TR000114 and UL1RR024131 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) to UCLA/LA BioMed, to the University of Minnesota, and to the Children’s Hospital Research Center, Oakland, Clinical and Translational Science Institutes (CTSI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CTSI or the NIH. Publisher Copyright: © 2019, The Author(s).

PY - 2020/1/1

Y1 - 2020/1/1

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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Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation

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