{"doi":"10.1016/j.ymgme.2006.12.012","title":"Intrathecal enzyme replacement therapy: Successful treatment of brain disease via the cerebrospinal fluid","abstract":null,"journal":"Molecular Genetics and Metabolism","year":2007,"id":623250,"datarank":0.7640625301210144,"base_score":5.093750200806762,"endowment":5.093750200806762,"self_citation_contribution":0.7640625301210144,"citation_network_contribution":0.0,"self_endowment_contribution":0.7640625301210144,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":162,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1610659,"name":"Michael McEntee","orcid":null,"position":1,"is_corresponding":false},{"id":114046,"name":"Carole Vogler","orcid":null,"position":2,"is_corresponding":false},{"id":114477,"name":"Steven Le","orcid":null,"position":3,"is_corresponding":false},{"id":114049,"name":"Beth Levy","orcid":null,"position":4,"is_corresponding":false},{"id":1610660,"name":"Maryn Peinovich","orcid":null,"position":5,"is_corresponding":false},{"id":1610661,"name":"Stephen Hanson","orcid":null,"position":6,"is_corresponding":false},{"id":114476,"name":"Merry Passage","orcid":null,"position":7,"is_corresponding":false},{"id":113213,"name":"Emil Kakkis","orcid":null,"position":8,"is_corresponding":false},{"id":471360,"name":"Patricia Dickson","orcid":"0000-0003-3467-8488","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Intrathecal enzyme replacement therapy: Successful treatment of brain disease via the cerebrospinal fluid","abstract":"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 iduronidase (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.","is_dataset_classified":null,"base_score":5.093750200806762,"endowment":5.093750200806762,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17321776","pmcid":"PMC3009387","openalex_id":"https://openalex.org/W2048686056","authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS054242","title":null}],"total_grants":1,"fwci":9.1021,"citation_percentile":0.98595911,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":14},{"year":2014,"count":12},{"year":2015,"count":11},{"year":2016,"count":3},{"year":2017,"count":11},{"year":2018,"count":4},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":2},{"year":2022,"count":3},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"green","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3009387","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3009387","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S1096719207000029?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1096719207000029?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ymgme.2006.12.012","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17321776","host_type":"repository"},{"url":"http://europepmc.org/abstract/MED/17321776","host_type":"repository"}],"fields_of_study":["Lysosomal Storage Disorders Research","Alcoholism and Thiamine Deficiency","Glycogen Storage Diseases and Myoclonus","Animals","Brain","Brain Diseases","Disease Models, Animal","Dogs","Dose-Response Relationship, Drug","Glycosaminoglycans","Humans","Iduronidase","Injections, Spinal","Meninges","Mucopolysaccharidosis I","Recombinant Proteins","Spinal Cord","Tissue Distribution"],"mesh_terms":["Animals","Brain","Brain Diseases","Disease Models, Animal","Dogs","Dose-Response Relationship, Drug","Glycosaminoglycans","Humans","Iduronidase","Injections, Spinal","Mucopolysaccharidosis I","Meninges","Recombinant Proteins","Spinal Cord","Tissue Distribution"],"keywords":["Intrathecal","Cerebrospinal fluid","Medicine","Enzyme replacement therapy","Disease","Surgery","Pathology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T22:58:08.555523Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}