{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:47:09Z","timestamp":1791974829469,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Frontotemporal dementia (FTD) is the second most common cause of early\u2010onset dementia after Alzheimer's disease, characterized by substantial genetic, clinical, and pathological heterogeneity. Despite progress in understanding its pathophysiology, no disease\u2010targeted therapies (DTTs) have been approved to date. This study provides an updated overview of ongoing and completed clinical trials in FTD, analyzing therapeutic strategies, trial phases, and molecular targets. All registered trials were systematically searched on the online registers ClinicalTrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform, using the search terms \u201cFrontotemporal Dementia,\u201d \u201cFTD,\u201d and \u201csvPPA\u201d (semantic variant primary progressive aphasia). Included studies investigated pharmacological or cell\u2010based interventions in Phases 1 through 4 or in trials with no reported phase. Non\u2010pharmacological and biomarker\u2010only trials were excluded. The Common Alzheimer's Disease Research Ontology (CADRO) was used to classify mechanisms of action. Data were collected as of February 3, 2026. A total of 49 trials were identified, investigating 35 pharmacological and three cell interventions. Among them, 16 trials (32.7%) were still active and had an expected sample size of 1036 participants. More than half of the pharmacological interventions investigated were classified as DTTs (67.3%), targeting specifically\n                    <jats:italic>GRN<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>C9orf72<\/jats:italic>\n                    \u2010associated genetic forms of FTD, while 26.5% targeted symptomatic treatments, addressing behavioral and neuropsychiatric symptoms. Seventeen molecules (32.7%) were repurposed drugs. The pipeline for the development of new potential treatments for FTD is still limited, with a predominant focus on rare genetic forms and a limited number of trials addressing sporadic FTD. Many trials remain inactive or unpublished, hindering translational progress. The scarcity of reliable biomarkers and the exclusion of patients without access to genetic testing further limits trial inclusivity. Improving biomarker research, trial transparency, and global accessibility are critical steps toward developing effective, scalable therapies for FTD.\n                  <\/jats:p>","DOI":"10.1002\/trc2.70243","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:03:32Z","timestamp":1791972212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic intervention strategies in frontotemporal dementia: drug development pipeline"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4079-8972","authenticated-orcid":false,"given":"Federica","family":"Perrone","sequence":"first","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Locuratolo","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Cappella","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Rivabene","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Fabrizi","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Talarico","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Vanacore","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Lacorte","sequence":"additional","affiliation":[{"name":"National Center for Disease Prevention and Health Promotion Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Italian National Institute of Health  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(19)30394\u20101"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2025.3307"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002638"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2349286"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010021\u201000878\u2010y"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010020\u20100330\u2010x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13363"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010024\u201000737\u20105"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010019\u201009363\u20104"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002973\u20100"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004251\u2010y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12179"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259\u2010023\u201000633\u20102"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.05.002"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.05.008"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2018.03.009"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2016.07.001"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.70098"},{"key":"e_1_2_7_20_1","unstructured":"AADvac1 | ALZFORUM. Accessed December 2 2025.https:\/\/www.alzforum.org\/therapeutics\/aadvac1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(14)70088\u20102"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010023\u201000523\u2010w"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191173"},{"key":"e_1_2_7_24_1","volume-title":"Wave Life Sciences Discontinues C9orf72\u2010ALS and Frontotemporal Dementia Agent WVE\u2010004 After Disappointing Phase 1b\/2a Findings","author":"Meglio M","year":"2023"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.25584"},{"key":"e_1_2_7_26_1","volume-title":"Latozinemab Shows No Impact on Disease Progression in C9orf72 Frontotemporal Dementia Despite increasing Progranulin Expression","author":"Meglio M","year":"2023"},{"key":"e_1_2_7_27_1","volume-title":"Alector Announces Topline Results from Latozinemab Phase 3 Trial in Individuals with Frontotemporal Dementia Due to a GRN Mutation and Provides Business Update","author":"LLC A","year":"2025"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv133"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4088\/jcp.v69n1219a"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113034"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191265"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001133"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3284"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70320\u20104"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00087"},{"key":"e_1_2_7_36_1","unstructured":"TherapeuticsT.Transposon Announces final results from a phase 2 study of TPN\u2010101 for the treatment of C9orf72\u2010related amyotrophic lateral sclerosis and\/or frontotemporal dementia. Accessed September 2 2025.https:\/\/www.prnewswire.com\/news\u2010releases\/transposon\u2010announces\u2010final\u2010results\u2010from\u2010a\u2010phase\u20102\u2010study\u2010of\u2010tpn\u2010101\u2010for\u2010the\u2010treatment\u2010of\u2010c9orf72\u2010related\u2010amyotrophic\u2010lateral\u2010sclerosis\u2010andor\u2010frontotemporal\u2010dementia\u2010302204851.html"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411450"},{"key":"e_1_2_7_38_1","unstructured":"AADvac1 | ALZFORUM. Accessed August 19 2025.https:\/\/www.alzforum.org\/therapeutics\/aadvac1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00284\u20109"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010121606"},{"key":"e_1_2_7_41_1","unstructured":"AL001 boosts progranulin. Does it slow frontotemporal dementia? ALZFORUM. Accessed November 25 2025.https:\/\/www.alzforum.org\/news\/conference\u2010coverage\/al001\u2010boosts\u2010progranulin\u2010does\u2010it\u2010slow\u2010frontotemporal\u2010dementia"},{"key":"e_1_2_7_42_1","unstructured":"DNL593. ALZFORUM. Accessed February 3 2026.https:\/\/www.alzforum.org\/therapeutics\/dnl593"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3284"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00456\u20103"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081658"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010020\u201002252\u20105"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.20517\/and.2024.32"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010023\u201003499\u2010x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.32604\/biocell.2022.017248"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2017.0148"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00317"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v12.i2.100"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010023\u201001344\u20106"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197013"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010025\u201001813\u20108"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001271\u20102"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.neuropsych.21060166"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70989"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1578252"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(21)00341\u20100"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010022\u201001260\u20105"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104698"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13129"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2023.2284305"}],"container-title":["Alzheimer's &amp; Dementia: Translational Research &amp; Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70243","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/trc2.70243","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:03:35Z","timestamp":1791972215000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/trc2.70243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/trc2.70243"],"URL":"https:\/\/doi.org\/10.1002\/trc2.70243","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70243"}}