A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II
| Autor: | Ann J. Barbier, Suresh Vijayaraghavan, Mary Ann Mascelli, Nan Wang, Joseph Muenzer, Christian J. Hendriksz, Saikat Santra, Victor Perry, Kenneth Sciarappa, Zheng Fan, Guirish A. Solanki, Luying Pan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Mucopolysaccharidosis II Idursulfase Iduronate Sulfatase Intrathecal law.invention 03 medical and health sciences Randomized controlled trial law medicine Humans Enzyme Replacement Therapy Child Injections Spinal Genetics (clinical) Glycosaminoglycans business.industry Enzyme replacement therapy Clinical trial 030104 developmental biology Phase i ii Child Preschool Anesthesia Female business medicine.drug |
| Zdroj: | Genetics in Medicine. 18:73-81 |
| ISSN: | 1098-3600 |
| DOI: | 10.1038/gim.2015.36 |
| Popis: | Approximately two-thirds of patients with the lysosomal storage disease mucopolysaccharidosis II have progressive cognitive impairment. Intravenous (i.v.) enzyme replacement therapy does not affect cognitive impairment because recombinant iduronate-2-sulfatase (idursulfase) does not penetrate the blood-brain barrier at therapeutic concentrations. We examined the safety of idursulfase formulated for intrathecal administration (idursulfase-IT) via intrathecal drug delivery device (IDDD). A secondary endpoint was change in concentration of glycosaminoglycans in cerebrospinal fluid. Sixteen cognitively impaired males with mucopolysaccharidosis II who were previously treated with weekly i.v. idursulfase 0.5 mg/kg for ≥6 months were enrolled. Patients were randomized to no treatment or 10-mg, 30-mg, or 1-mg idursulfase-IT monthly for 6 months (four patients per group) while continuing i.v. idursulfase weekly. No serious adverse events related to idursulfase-IT were observed. Surgical revision/removal of the IDDD was required in 6 of 12 patients. Twelve total doses were administrated by lumbar puncture. Mean cerebrospinal fluid glycosaminoglycan concentration was reduced by approximately 90% in the 10-mg and 30-mg groups and approximately 80% in the 1-mg group after 6 months. These preliminary data support further development of investigational idursulfase-IT in MPS II patients with the severe phenotype who have progressed only to a mild-to-moderate level of cognitive impairment.Genet Med advance online publication 02 April 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.36. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink