Safety of laronidase delivered into the spinal canal for treatment of cervical stenosis in mucopolysaccharidosis I.

Autor: Dickson PI; Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States. Electronic address: pdickson@ucla.edu., Kaitila I; Medical Genetics, University of Helsinki, Helsinki University Hospital, Helsinki, Finland., Harmatz P; UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States., Mlikotic A; Department of Radiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States., Chen AH; 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., Victoroff A; Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States., Passage MB; Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States., Madden J; UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States., Le SQ; Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States., Naylor DE; Department of Neurology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2015 Sep-Oct; Vol. 116 (1-2), pp. 69-74. Date of Electronic Publication: 2015 Jul 26.
DOI: 10.1016/j.ymgme.2015.07.005
Abstrakt: 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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