{"doi":"10.1016/j.ymgme.2008.01.014","title":"Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis","abstract":null,"journal":"Molecular Genetics and Metabolism","year":2008,"id":648569,"datarank":2.038841199821165,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":1.4432974127883467,"self_endowment_contribution":0.5955437870328184,"citer_contribution":1.4432974127883467,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":40,"citers_with_citation_signal":36,"citers_with_endowment":36,"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":1690292,"name":"Mukarram El-Banna","orcid":null,"position":1,"is_corresponding":false},{"id":1690294,"name":"Istvan Sohar","orcid":null,"position":2,"is_corresponding":false},{"id":1690296,"name":"Kwi-Hye Kim","orcid":null,"position":3,"is_corresponding":false},{"id":667845,"name":"Kostantin Dobrenis","orcid":"0000-0001-7495-2475","position":4,"is_corresponding":false},{"id":667844,"name":"Steven U. Walkley","orcid":"0000-0003-2279-8597","position":5,"is_corresponding":false},{"id":399854,"name":"Peter Lobel","orcid":"0000-0003-3148-2471","position":6,"is_corresponding":false},{"id":399852,"name":"David E. Sleat","orcid":"0000-0002-5159-9928","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis","abstract":"Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary neurodegenerative disease of childhood that is caused by mutations in the gene (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is fatal and there is no treatment of demonstrated efficacy in affected children but preclinical studies with AAV-mediated gene therapy have demonstrated promise in a mouse model. Here, we have generated mouse CLN2-mutants that express different amounts of TPPI activity to benchmark levels required for therapeutic benefits. Approximately 3% of normal TPPI activity in brain delayed disease onset and doubled lifespan to a median of approximately 9 months compared to mice expressing approximately 0.2% of normal levels. Expression of 6% of normal TPPI activity dramatically attenuated disease, with a median lifespan of approximately 20 months which approaches that of unaffected mice. While the lifespan of this hypomorph is shortened, disease is late-onset, less severe and progresses slowly compared to mice expressing lower TPPI levels. For gene therapy and other approaches that restore enzyme activity, these results suggest that 6% of normal TPPI activity throughout the CNS of affected individuals will provide a significant therapeutic benefit but higher levels will be required to cure this disease.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18343701","pmcid":"PMC2467442","openalex_id":null,"authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"NS37918","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"R01 HD045561","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS037918","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"HD045561","title":null}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2467442","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S1096719208000176?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1096719208000176?httpAccept=text/plain","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Liver","Brain","Lysosomes","Animals","Mice, Transgenic","Mice","Disease Models, Animal","Mitochondrial Proton-Translocating ATPases","Endopeptidases","Aminopeptidases","Gene Targeting","Species Specificity","Neuronal Ceroid-Lipofuscinoses","Dipeptidyl-Peptidases and Tripeptidyl-Peptidases","Serine Proteases","Genetic Therapy","Tripeptidyl-Peptidase 1"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:45:35.971579Z","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":[]}