{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:54:45Z","timestamp":1791507285231,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health-National Institute","award":["R01 AG062463"],"award-info":[{"award-number":["R01 AG062463"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: We previously demonstrated that nilotinib can sufficiently enter the brain to pharmacologically inhibit discoidin domain receptors (DDR)-1 in patients with Parkinson\u2019s and Alzheimer\u2019s 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 \u00b1 SD) was 73 \u00b1 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\/A\u03b242 was reduced (p = 0.034). The Alzheimer\u2019s Disease Assessment Scale\u2014cognition 14 improved by 2.8 pts (p = 0.037), and no differences were observed in Movement Disorders Society\u2013Unified Parkinson\u2019s 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\u2019s disease with dementia.<\/jats:p>","DOI":"10.3390\/jcm14124245","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T06:40:27Z","timestamp":1750056027000},"page":"4245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety, Cognitive, and Behavioral Outcomes in Patients with Dementia with Lewy Bodies Treated with Nilotinib"],"prefix":"10.3390","volume":"14","author":[{"given":"Fernando","family":"Pagan","sequence":"first","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"},{"name":"Department of Neurology, Movement Disorders Clinic, MedStar Georgetown University Hospital, PHC 7, 3300 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasar","family":"Torres-Yaghi","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"},{"name":"Department of Neurology, Movement Disorders Clinic, MedStar Georgetown University Hospital, PHC 7, 3300 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaeline","family":"Hebron","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wilmarth","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"},{"name":"Department of Neurology, Movement Disorders Clinic, MedStar Georgetown University Hospital, PHC 7, 3300 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Scott","family":"Turner","sequence":"additional","affiliation":[{"name":"Memory Disorders Program, Department of Neurology, Georgetown University Medical Center, Suite 177, Building D, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Matar","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine, Department of Radiology, MedStar Georgetown Hospital, Bles Building, 2nd Floor, 3300 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7998-4759","authenticated-orcid":false,"given":"Jaeil","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Basic Science Building, 3800 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-7063","authenticated-orcid":false,"given":"Charbel","family":"Moussa","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology, Lewy Body Dementia Association Research Center of Excellence, Georgetown University Medical Center, Building D, Room 265, 4000 Reservoir Rd NW, Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/B978-0-12-802973-2.00009-4","article-title":"Epidemiology of alpha-synucleinopathies: From Parkinson disease to dementia with Lewy bodies","volume":"138","author":"Savica","year":"2016","journal-title":"Handb. Clin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13195-018-0350-6","article-title":"Clinical prevalence of Lewy body dementia","volume":"10","author":"Kane","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ccr.2005.01.007","article-title":"Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl","volume":"7","author":"Weisberg","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/ana.25775","article-title":"Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer\u2019s Disease","volume":"88","author":"Turner","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1001\/jamaneurol.2019.4200","article-title":"Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial","volume":"77","author":"Pagan","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12974-023-02802-0","article-title":"Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer\u2019s disease","volume":"20","author":"Stevenson","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3233\/JPD-160867","article-title":"Nilotinib Effects in Parkinson\u2019s disease and Dementia with Lewy bodies","volume":"6","author":"Pagan","year":"2016","journal-title":"J. Parkinsons Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1001\/jamaneurol.2020.4725","article-title":"Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial","volume":"78","author":"Simuni","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/mds.28389","article-title":"Long-Term Safety and Clinical Effects of Nilotinib in Parkinson\u2019s Disease","volume":"36","author":"Pagan","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","article-title":"Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium","volume":"89","author":"McKeith","year":"2017","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ncl.2019.12.001","article-title":"Clinical Rating Scales and Quantitative Assessments of Movement Disorders","volume":"38","author":"Tarakad","year":"2020","journal-title":"Neurol. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1176\/ajp.141.11.1356","article-title":"A new rating scale for Alzheimer\u2019s disease","volume":"141","author":"Rosen","year":"1984","journal-title":"Am. J. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1212\/WNL.0000000000004826","article-title":"Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology","volume":"90","author":"Petersen","year":"2018","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1177\/1533317515603359","article-title":"Assessing Fluctuating Cognition in Dementia Diagnosis: Interrater Reliability of the Clinician Assessment of Fluctuation","volume":"31","author":"Towns","year":"2016","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Demen"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.psychres.2007.03.002","article-title":"The Irritability Questionnaire: A new scale for the measurement of irritability","volume":"159","author":"Craig","year":"2008","journal-title":"Psychiatry Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3233\/JHD-150164","article-title":"Exploring the Validity of the Short Version of the Problem Behaviours Assessment (PBA-s) for Huntington\u2019s disease: A Rasch Analysis","volume":"4","author":"McNally","year":"2015","journal-title":"J. Huntingt. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1212\/WNL.48.5_Suppl_6.10S","article-title":"The Neuropsychiatric Inventory: Assessing psychopathology in dementia patients","volume":"48","author":"Cummings","year":"1997","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jamda.2016.10.008","article-title":"Falls, Cognitive Impairment, and Gait Performance: Results From the GOOD Initiative","volume":"18","author":"Allali","year":"2017","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/JAD-180094","article-title":"Ventral Tegmental Area in Prodromal Alzheimer\u2019s Disease: Bridging the Gap between Mice and Humans","volume":"63","author":"Serra","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14727","DOI":"10.1038\/ncomms14727","article-title":"Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer\u2019s disease","volume":"8","author":"Nobili","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E.C., Cutuli, D., Cauzzi, E., Marino, R., and Viscomi, M.T. (2021). Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer\u2019s Disease. Prog. Neurobiol., 202.","DOI":"10.1016\/j.pneurobio.2021.102031"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1136\/jnnp-2017-316385","article-title":"Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating dementia with Lewy bodies from Alzheimer\u2019s disease at the prodromal stage","volume":"89","author":"Bousiges","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/exnr.1997.6761","article-title":"The spatial patterns of Lewy bodies, senile plaques, and neurofibrillary tangles in dementia with Lewy bodies","volume":"150","author":"Armstrong","year":"1998","journal-title":"Exp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1006\/bbrc.1997.6908","article-title":"Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology","volume":"236","author":"Arai","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3233\/JAD-2011-110482","article-title":"CSF tau, Abeta42, and MHPG differentiate dementia with Lewy bodies from Alzheimer\u2019s disease","volume":"27","author":"Aerts","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2017.07.009","article-title":"Discoidin domain receptor inhibition reduces neuropathology and attenuates inflammation in neurodegeneration models","volume":"311","author":"Hebron","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e633","DOI":"10.1212\/NXG.0000000000000633","article-title":"CSF MicroRNAs Reveal Impairment of Angiogenesis and Autophagy in Parkinson Disease","volume":"7","author":"Fowler","year":"2021","journal-title":"Neurol. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tie, Y., Tang, F., Peng, D., Zhang, Y., and Shi, H. (2022). TGF-beta signal transduction: Biology, function and therapy for diseases. Mol. Biomed., 3.","DOI":"10.1186\/s43556-022-00109-9"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1749-6632.1999.tb07675.x","article-title":"Insights into MMP-TIMP interactions","volume":"878","author":"Bode","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neures.2015.01.004","article-title":"DDR1 may play a key role in destruction of the blood-brain barrier after cerebral ischemia-reperfusion","volume":"96","author":"Zhu","year":"2015","journal-title":"Neurosci. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1681\/ASN.2018111160","article-title":"The Extracellular Matrix Receptor Discoidin Domain Receptor 1 Regulates Collagen Transcription by Translocating to the Nucleus","volume":"30","author":"Chiusa","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1681\/ASN.2006060677","article-title":"Discoidin domain receptor 1 null mice are protected against hypertension-induced renal disease","volume":"17","author":"Flamant","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1164\/rccm.200603-333OC","article-title":"Discoidin domain receptor 1-deficient mice are resistant to bleomycin-induced lung fibrosis","volume":"174","author":"Singal","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:09Z","timestamp":1760032329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,14]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14124245"],"URL":"https:\/\/doi.org\/10.3390\/jcm14124245","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,14]]}}}