title: Safety of laronidase delivered into the spinal canal for treatment of cervical stenosis in mucopolysaccharidosis I.
abstract: Enzyme replacement therapy with laronidase (recombinant human alpha-l-iduronidase) is successfully used to treat patients with mucopolysaccharidosis type I (MPS I). However, the intravenously-administered enzyme is not expected to treat or prevent neurological deterioration. As MPS I patients suffer from spinal cord compression due in part to thickened spinal meninges, we undertook a phase I clinical trial of lumbar intrathecal laronidase in MPS I subjects age 8 years and older with symptomatic (primarily cervical) spinal cord compression. The study faced significant challenges, including a heterogeneous patient population, difficulty recruiting subjects despite an international collaborative effort, and an inability to include a placebo-controlled design due to ethical concerns. Nine serious adverse events occurred in the subjects. All subjects reported improvement in symptomatology and showed improved neurological examinations, but objective outcome measures did not demonstrate change. Despite limitations, we demonstrated the safety of this approach to treating neurological disease due to MPS I.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States. Electronic address: pdickson@ucla.edu.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
authors.affiliation: Medical Genetics, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kaitila
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Department of Radiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: Anton
authors.initials: A
authors.lastname: Mlikotic
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States; Department of Neurology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: Agnes H
authors.initials: AH
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: Alla
authors.initials: A
authors.lastname: Victoroff
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: Merry B
authors.initials: MB
authors.lastname: Passage
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Madden
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: Steven Q
authors.initials: SQ
authors.lastname: Le
authors.affiliation: Department of Neurology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Naylor
mesh_terms: D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology*; D002648:Child; D003251:Constriction, Pathologic / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013115:Spinal Canal / Q000187:drug effects; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase
keywords: Alpha-l-iduronidase; Enzyme replacement therapy; Hurler; Intrathecal; Lysosomal storage disease; Scheie