{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:21:35Z","timestamp":1777396895691,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) and progressive supranuclear palsy (PSP) are major neurodegenerative conditions with tau pathology in common but distinct symptoms\u2014AD involves cognitive decline while PSP affects balance and eye movement. Progranulin (PGRN) is a growth factor implicated in neurodegenerative diseases, including AD and PSP. AZP2006, a synthetic compound, targets tauopathies by stabilizing PGRN levels and reducing tau aggregation and neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Evaluate the safety, tolerability, and pharmacokinetics of AZP2006.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A first-in-Human phase 1 study comprised a single ascending dose (SAD) and a multiple ascending dose study (MAD). The SAD study included 64 healthy male volunteers and tested singles oral doses of 3 to 500\u200amg of AZP2006 free base equivalent or placebo. In the MAD study, 24 healthy male volunteers were administered oral doses of 30, 60, and 120\u200amg per day of AZP2006 or placebo for 10 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>No serious adverse events were observed. Clinical, biological, and electrocardiogram findings were non-relevant. Nineteen minor adverse events resolved before study completion. The safety profile indicated no specific risks. The multiple ascending dose study was halted, and the optional dose level of 180\u200amg was not performed due to high levels of M2 metabolite in plasma that necessitated additional preclinical evaluation of M2. Both AZP2006 and its M2 metabolite were quickly absorbed and widely distributed in tissues. Exposure increased more than proportionally with dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>AZP2006 had a favorable safety profile and was rapidly absorbed. Elevated M2 metabolite levels necessitated further studies to clarify excretion and metabolism mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-220883","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T10:55:05Z","timestamp":1709031305000},"page":"715-727","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["First-In-Human Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of AZP2006, A Synthetic Compound for the Treatment of Alzheimer\u2019s Disease and Related Diseases"],"prefix":"10.1177","volume":"98","author":[{"given":"Philippe","family":"Verwaerde","sequence":"first","affiliation":[{"name":"Alzprotect sas, Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Estrella","sequence":"additional","affiliation":[{"name":"Alzprotect sas, Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Burlet","sequence":"additional","affiliation":[{"name":"Alzprotect sas, Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Barrier","sequence":"additional","affiliation":[{"name":"Alzprotect sas, Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9e-Anne","family":"Marotte","sequence":"additional","affiliation":[{"name":"Alzprotect sas, Loos, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Clincke","sequence":"additional","affiliation":[{"name":"Independent Scientific Consultant"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-011-9589-0"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2017.01.001"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-020-2282-1"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70042-0"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94708-1"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8030230"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.399170"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0132-1"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2016"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0288-y"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1861-8"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0196-6"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab310"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn5003013"},{"key":"e_1_3_5_16_2","first-page":"74539","article-title":"Tau phosphorylation, aggregation, and cell toxicity","volume":"2006","author":"Avila J","year":"2006","unstructured":"AvilaJ, Santa-Mar\u00edaI, P\u00e9rezM, Hern\u00e1ndezF, MorenoF (2006) Tau phosphorylation, aggregation, and cell toxicity. 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