{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:59:33Z","timestamp":1789714773395,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Pharmacological restoration of septin filament integrity has the potential to provide symptomatic benefit and disease modification in Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      REM127, a septin modulator, was assessed in mild\u2010to\u2010moderate AD (EudraCT: 2022\u2010000080\u201043) in a phase 2a trial (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014). Primary endpoints: safety and tolerability; exploratory endpoints: pharmacokinetics, cerebrospinal fluid (CSF) biomarkers, electroencephalography (EEG), and functional outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In participants on active therapy, dose\u2010dependent increases in serum aminotransferase were observed, leading to study discontinuation. CSF hyperphosphorylated tau (P\u2010tau181), endpoints reflecting synaptic function and cognitive outcomes, were changed significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) to normal compared to placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>REM127 triggers off\u2010target liver adverse effects. Anticipated on\u2010target outcomes suggest septin modulation has symptomatic benefit and modifies processes underlying AD. Results are considered exploratory as statistical power is constrained due to the small sample size caused by early termination. Further investigation of the therapeutic concept using an optimized septin molecular glue with an improved safety profile is warranted.<\/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>Septin 6\/7 molecular glue REM127 was assessed in symptomatic participants with Alzheimer's disease (AD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>REM127 triggers off\u2010target effects suggesting liver adverse effects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>REM127 brain exposure was consistent with saturated target engagement.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Biomarker and cognitive outcomes were changed consistent with therapeutic benefit.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Septin modulation may restore synaptic function and mitigate pathology in AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70537","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T11:36:15Z","timestamp":1757676975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Mieke","family":"Nuytten","sequence":"first","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Voets","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline","family":"Debroux","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Princen","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lentel","family":"Pringels","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Fivaz","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Byl","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Ramael","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"De Witte","sequence":"additional","affiliation":[{"name":"remynd NV  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e9","family":"Boada","sequence":"additional","affiliation":[{"name":"Ace Alzheimer Center Barcelona\u2010Universitat Internacional de Catalunya  Les Corts Barcelona Spain"},{"name":"Pentara Corp.  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