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.
Bibliographical noteFunding 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.
Competing interests: L.E.P. is a speaker and consultant for Sanofi/Genzyme, receives research support from Sanofi/Genzyme and Shire, and is a consultant for Sangamo. T. C.L. receives research support from Sanofi/Genzyme. E.B. is a speaker for Sanofi/ Genzyme and receives research support from BioMarin and Bluebird Bio. B.S.M. is a consultant for AbbVie, Ascendis, Ferring, Novo Nordisk, Pfizer, Sandoz and Versartis and has received research support from Alexion, Ascendis, Endo Pharmaceuticals, Genentech, Genzyme, Novo Nordisk, Opko, Sandoz, Sangamo, Shire, Tolmar and Versartis. E.F. is a consultant for BioMarin Pharmaceuticals. C.B.W. is a consultant for Sanofi/Genzyme. J.B.E. has received honoraria, consulting fees, and/or research support from ArmaGen, Regenexbio, Sangamo, and Sanofi/Genzyme, and has done contract work for Shapiro Neuropsychology Consulting, LLC. W.P.M. is an employee of Sangamo Therapeutics. P.J.O. receives research and clinical trial support from Sanofi/ Genzyme, Horizon, Magenta and Bluebird Bio. The other authors declare no competing interests.
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural