{"doi":"10.1016/j.omtm.2025.101563","title":"AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy","abstract":". Here, we compared the effects of single-chain variable fragments (scFvs) derived from the well-characterized monoclonal antibodies PHF1 and MC1. We used adeno-associated virus 1 (AAV1) to deliver scFvs to skeletal muscle cells in 8-week-old P301S tau transgenic mice. We evaluated motor and behavioral functions at 16 and 23 weeks of age and measured misfolded, soluble, oligomeric, and insoluble brain tau species. Monotherapy with scFv-MC1 improved motor and behavioral functions more effectively than scFv-PHF1 or combination therapy. Brain glucose metabolism also benefited from scFv-MC1 treatment. Surprisingly, combining scFvs targeting early (MC1) and late (PHF1) tau modifications did not produce additive or synergistic effects. These results confirm that intramuscular AAV1-mediated scFv-MC1 gene therapy holds promise as a potential treatment for AD. Our findings also suggest that combining scFvs targeting different tau epitopes may not necessarily enhance efficacy if administered together in a prevention paradigm. Further research is needed to explore whether other antibodies' combinations and/or administration schedules could improve the efficacy of scFv-MC1 alone.","journal":"Molecular Therapy — Methods & Clinical Development","year":2025,"id":572377,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":234180,"name":"Julia Cicalo","orcid":null,"position":1,"is_corresponding":false},{"id":1478556,"name":"Valeria Vasciaveo","orcid":"0000-0001-9396-1940","position":2,"is_corresponding":false},{"id":662025,"name":"Laura M. Vecchio","orcid":"0000-0003-1520-9336","position":3,"is_corresponding":false},{"id":827142,"name":"Joseph Carrión","orcid":"0000-0003-2275-3196","position":4,"is_corresponding":false},{"id":1479019,"name":"Leann Mahadeo","orcid":null,"position":5,"is_corresponding":false},{"id":284706,"name":"Patricio T. Huerta","orcid":"0000-0003-0270-2308","position":6,"is_corresponding":false},{"id":1479020,"name":"Janvi D Choksi","orcid":null,"position":7,"is_corresponding":false},{"id":371449,"name":"Isabelle Aubert","orcid":"0000-0001-5163-9961","position":8,"is_corresponding":false},{"id":451439,"name":"Philippe Marambaud","orcid":"0000-0002-8983-1497","position":9,"is_corresponding":false},{"id":451440,"name":"Luca Giliberto","orcid":"0000-0002-6406-0964","position":10,"is_corresponding":false},{"id":451441,"name":"Cristina d’Abramo","orcid":"0000-0003-4470-4942","position":11,"is_corresponding":false},{"id":1479018,"name":"Sebica Katel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:57:23.653298Z","pmid":"40932994","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":[]}