title: Immune response to intrathecal enzyme replacement therapy in mucopolysaccharidosis I patients.
abstract: BACKGROUND
  Intrathecal (IT) enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) has been studied to treat glycosaminoglycan storage in the central nervous system of mucopolysaccharidosis (MPS) I dogs and is currently being studied in MPS I patients.
  
  
  METHODS
  We studied the immune response to IT rhIDU in MPS I subjects with spinal cord compression who had been previously treated with intravenous rhIDU. We measured the concentrations of specific antibodies and cytokines in serum and cerebrospinal fluid (CSF) collected before monthly IT rhIDU infusions and compared the serologic findings with clinical adverse event (AE) reports to establish temporal correlations with clinical symptoms.
  
  
  RESULTS
  Five MPS I subjects participating in IT rhIDU trials were studied. One subject with symptomatic spinal cord compression had evidence of an inflammatory response with CSF leukocytosis, elevated interleukin-5, and elevated immunoglobulin G. This subject also complained of lower back pain and buttock paresthesias temporally correlated with serologic abnormalities. Clinical symptoms were managed with oral medication, and serologic abnormalities were resolved, although this subject withdrew from the trial to have spinal decompressive surgery.
  
  
  CONCLUSIONS
  IT rhIDU was generally well tolerated in the subjects studied, although one subject had moderate to severe clinical symptoms and serologic abnormalities consistent with an immune response.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Moin
authors.initials: M
authors.lastname: Vera
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Le
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Kan
authors.affiliation: Department of Internal Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Hermes
authors.initials: H
authors.lastname: Garban
authors.affiliation: Department of Neurology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: David
authors.initials: D
authors.lastname: Naylor
authors.affiliation: Department of Radiology, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Anton
authors.initials: A
authors.lastname: Mlikotic
authors.affiliation: Departments of Medical Genetics and Pediatrics, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kaitila
authors.affiliation: Department of Pediatrics, Children's Hospital and Research Center Oakland, Oakland, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Agnes
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dickson
mesh_terms: D000328:Adult; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000627:therapeutic use*; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase