{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:35:11Z","timestamp":1791815711064,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":151,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bosutinib, a dual Abelson\/Src inhibitor, was investigated in individuals with dementia with Lewy bodies (DLB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single site, randomized, double\u2010blind, placebo\u2010controlled study of the effects of oral bosutinib, 100 mg once daily for 12 weeks on primary safety and pharmacokinetics and secondary biomarker outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010six participants were randomized and included male and female (12:1) in the bosutinib arm and all male (13) in the placebo arm. The average age was 72.9 \u00b1 8.1 (year \u00b1 standard deviation). There were no serious adverse events and no dropouts. Bosutinib was measured in the cerebrospinal fluid (CSF) and inhibited Abelson. Bosutinib reduced CSF alpha\u2010synuclein and dopamine catabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Bosutinib is safe and well tolerated and penetrates the blood\u2013brain barrier to inhibit Abelson and reduce CSF alpha\u2010synuclein and dopamine catabolism, suggesting that bosutinib (100 mg) may be at or near the lowest effective dose in DLB. These results will guide adequately powered studies to determine the efficacy of a dose range of bosutinib and longer treatment in DLB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Bosutinib is a dual Abl\/Src inhibitor that penetrates the blood brain barrier<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Bosutinib is safe and tolerated in individuals with dementia with Lewy bodies<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Bosutinib engages its target via inhibition of Abl and Src<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Bosutinib reduces CSF alpha\u2010synuclein and attenuates breakdown of dopamine<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Bosutinib improves activities of daily living in dementia with Lewy bodies<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12296","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T05:58:37Z","timestamp":1654063117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies"],"prefix":"10.1002","volume":"8","author":[{"given":"Fernando L.","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  Washington DC USA"},{"name":"MedStar Georgetown University Hospital Movement Disorders Clinic Department of Neurology  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasar","family":"Torres\u2010Yaghi","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  Washington DC USA"},{"name":"MedStar Georgetown University Hospital Movement Disorders Clinic Department of Neurology  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaeline L.","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  Washington DC 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  Washington DC USA"},{"name":"MedStar Georgetown University Hospital Movement Disorders Clinic Department of Neurology  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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