期刊
MOLECULAR GENETICS AND METABOLISM
卷 91, 期 1, 页码 61-68出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2006.12.012
关键词
mucopolysaccharidosis I; lysosomal storage disorder; intrathecal; enzyme replacement therapy; central nervous system; cerebrospinal fluid; Hurler; Scheie; Hurler-Scheie; pachymeningitis
资金
- NINDS NIH HHS [R01 NS054242, R01 NS054242-01A1] Funding Source: Medline
Treatment of brain disease with recombinant proteins is difficult due to the blood-brain barrier. As an alternative to direct injections into the brain, we studied whether application of high concentrations of therapeutic enzymes via intrathecal (IT) injections could successfully drive uptake across the ependyma to treat brain disease. We studied IT enzyme replacement therapy with recombinant human idu-ronidase (rhIDU) in canine mucopolysaccharidosis I (MPS I, Hurler syndrome), a lysosomal storage disorder with brain and meningeal involvement. Monthly or quarterly IT treatment regimens with rhIDU achieved supranormal iduronidase enzyme levels in the brain, spinal cord, and spinal meninges. All regimens normalized total brain glycosaminoglycan (GAG) storage and reduced spinal meningeal GAG storage by 58-70%. The improvement in GAG storage levels persisted three months after the final IT dose. The successful use of enzyme therapy via the CSF represents a potentially useful approach for lysosomal storage disorders. (C) 2007 Elsevier Inc. All rights reserved.
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