{"doi":"10.3390/jcm14124245","title":"Safety, Cognitive, and Behavioral Outcomes in Patients with Dementia with Lewy Bodies Treated with Nilotinib","abstract":"Background/Objectives: We previously demonstrated that nilotinib can sufficiently enter the brain to pharmacologically inhibit discoidin domain receptors (DDR)-1 in patients with Parkinson’s and Alzheimer’s disease. We primarily hypothesized that nilotinib is safe, and may alter disease-related biomarkers to improve, motor, cognitive and/or behavioral features in dementia with Lewy bodies (DLB). Methods: Forty-three participants were randomized 1:1 into nilotinib, 200 mg, or matching placebo in a single-center, phase 2, randomized, double-blind study. Study drug was taken orally once daily for 6 months followed by one-month wash-out. Results: Of 43 individuals enrolled, 14 were women (33%); age (mean ± SD) was 73 ± 8.5 years. Nilotinib was safe and well-tolerated, and more adverse events were noted in the placebo (74) vs. nilotinib (37) groups (p = 0.054). The number of falls were reduced in the nilotinib (six) compared to placebo (21) group (p = 0.006). Cerebrospinal fluid homovanillic acid, a biomarker of dopamine levels, was increased (p = 0.004), while the ratio of pTau181/Aβ42 was reduced (p = 0.034). The Alzheimer’s Disease Assessment Scale—cognition 14 improved by 2.8 pts (p = 0.037), and no differences were observed in Movement Disorders Society–Unified Parkinson’s Disease Rating Scale parts II and III. However, part I (cognition) improved (p = 0.044) in nilotinib compared to placebo. Conclusions: Nilotinib demonstrates favorable safety, biomarkers, and efficacy outcomes in patients with DLB supporting further trials in DLB or advanced Parkinson’s disease with dementia.","journal":"Journal of Clinical Medicine","year":2025,"id":538282,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"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":269681,"name":"Yasar Torres‐Yaghi","orcid":"0000-0002-9676-3832","position":1,"is_corresponding":false},{"id":272546,"name":"Michaeline Hebron","orcid":null,"position":2,"is_corresponding":false},{"id":455923,"name":"Barbara Wilmarth","orcid":null,"position":3,"is_corresponding":false},{"id":269676,"name":"Raymond Scott Turner","orcid":"0000-0001-7534-2935","position":4,"is_corresponding":false},{"id":269682,"name":"Sara Matar","orcid":"0000-0003-3478-4627","position":5,"is_corresponding":false},{"id":252171,"name":"Xiaoguang Liu","orcid":"0000-0001-6977-5128","position":6,"is_corresponding":false},{"id":272551,"name":"Dalila Ferrante","orcid":null,"position":7,"is_corresponding":false},{"id":269683,"name":"Giuseppe Esposito","orcid":"0000-0001-8080-8218","position":8,"is_corresponding":false},{"id":269686,"name":"Jaeil Ahn","orcid":"0000-0001-7998-4759","position":9,"is_corresponding":false},{"id":269687,"name":"Charbel Moussa","orcid":"0000-0002-2012-7063","position":10,"is_corresponding":false},{"id":269680,"name":"Fernando Pagán","orcid":"0000-0002-4052-156X","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:52:21.389196Z","pmid":"40565990","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":[]}