{"doi":"10.1002/jimd.12311","title":"A pilot study of neonatal <scp><i>GALT</i></scp> gene replacement using <scp>AAV9</scp> dramatically lowers galactose metabolites in blood, liver, and brain and minimizes cataracts in <scp>GALT</scp>‐null rat pups","abstract":"Classic galactosemia (CG) is a rare metabolic disorder that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection by newborn screening and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad constellation of long-term complications. The mechanisms underlying these complications remain unclear and likely differ by tissue. Here we conducted a pilot study testing the safety and efficacy of GALT gene replacement using our recently-described GALT-null rat model for CG. Specifically, we administered AAV9.CMV.HA-hGALT to seven GALT-null rat pups via tail vein injection on day 3 of life; eight GALT-null pups injected with PBS served as the negative control, and four GALT+ heterozygous pups injected with PBS served as the positive control. All pups were returned to their nursing mothers, weighed daily, and euthanized for tissue collection 2 weeks later. Among the AAV9-injected pups in this study, we achieved GALT levels in liver ranging from 64% to 595% wild-type, and in brain ranging from 3% to 42% wild-type. In liver, brain, and blood samples from these animals we also saw a striking drop in galactose, galactitol, and gal-1P. Finally, all treated GALT-null pups showed dramatic improvement in cataracts relative to their mock-treated counterparts. Combined, these results demonstrate that GALT restoration in both liver and brain of GALT-null rats by neonatal tail vein administration using AAV9 is not only attainable but effective.","journal":"Journal of Inherited Metabolic Disease","year":2020,"id":70598,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":375158,"name":"Jennifer M. I. Daenzer","orcid":null,"position":1,"is_corresponding":false},{"id":373638,"name":"Judith L. Fridovich‐Keil","orcid":"0000-0001-7947-5807","position":2,"is_corresponding":false},{"id":375157,"name":"Shauna A. Rasmussen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-18T21:43:32.585486Z","pmid":"32882063","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":[]}