{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:48:04Z","timestamp":1791092884930,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S034676\/1"],"award-info":[{"award-number":["MR\/S034676\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To extend the findings of a previous clinical trial suggesting combined abacavir (ABC), lamivudine (3TC), and zidovudine (AZT) reduces type I interferon (IFN) signalling in Aicardi\u2013Gouti\u00e8res syndrome (AGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This was an open label, non\u2010placebo\u2010controlled phase II clinical trial (NCT04731103) in patients less than 16\u2009years with any of five AGS genotypes. The effect of ABC or 3TC individually, or of combined ABC\u2009+\u20093TC\u2009+\u2009AZT, on IFN\u2010stimulated gene (ISG) expression (primary outcome) and IFN\u2010alpha protein (secondary outcome) in blood was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen patients were recruited. Compliance was poor in the ABC\u2009+\u20093TC\u2009+\u2009AZT arm. No statistically significant effects were observed with ABC or 3TC, or with ABC\u2009+\u20093TC\u2009+\u2009AZT over 6\u2009weeks. A statistically significant reduction of ISG expression was recorded after 3\u2009weeks of ABC\u2009+\u20093TC\u2009+\u2009AZT, which was not mirrored by changes in IFN\u2010alpha protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>There is insufficient evidence that ABC or 3TC is either effective or ineffective in reducing type I IFN signalling in AGS over 6\u2009weeks. The effect of ABC\u2009+\u20093TC\u2009+\u2009AZT at 3\u2009weeks supports data from a previous clinical trial of the effect of ABC\u2009+\u20093TC\u2009+\u2009AZT in reducing type I IFN signalling, although there was insufficient evidence of an effect at 6\u2009weeks. Time to local research and development (R&amp;D) approval, and to sponsor authorization after R&amp;D approval, severely limited patient recruitment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.16199","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T19:29:35Z","timestamp":1733340575000},"page":"750-757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reverse transcriptase inhibitors in Aicardi\u2013Gouti\u00e8res syndrome: A crossover clinical trial"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7211-7564","authenticated-orcid":false,"given":"Yanick J.","family":"Crow","sequence":"first","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Cancer University of Edinburgh  Edinburgh UK"},{"name":"Laboratory of Neurogenetics and Neuroinflammation Imagine Institute, INSERM UMR1163  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Briggs","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre The University of Manchester  Manchester UK"},{"name":"Department of Genomic Medicine St Marys Hospital, Manchester Foundation Trust  Manchester UK"},{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Eleftheriou","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Department University College London Great Ormond Street Institute of Child Health  London UK"},{"name":"Paediatric Rheumatology Department Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitav","family":"Parida","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Birmingham Children's Hospital, Birmingham Women and Children's Hospital Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Battison","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Giddings","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titouan","family":"Kennel","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Parker","sequence":"additional","affiliation":[{"name":"Edinburgh Clinical Trials Unit, Usher Institute University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"AGS\u2010RTIs Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3850"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-8-91"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2872"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1810983"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70258-8"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200600"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161451"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847060-00001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936010-00004"},{"key":"e_1_2_9_11_1","unstructured":"Britain's Covid research led the world \u2013 why have our clinical trials fallen off a cliff? Andrew Pollard.https:\/\/www.theguardian.com\/commentisfree\/2023\/apr\/26\/britain\u2010covid\u2010research\u2010clinical\u2010trials\u2010nhs\u2010doctors."},{"key":"e_1_2_9_12_1","unstructured":"Commercial clinical trials in the UK: the Lord O'Shaughnessy review \u2013 final report. May 2023.https:\/\/www.gov.uk\/government\/publications\/commercial\u2010clinical\u2010trials\u2010in\u2010the\u2010uk\u2010the\u2010lord\u2010oshaughnessy\u2010review\/commercial\u2010clinical\u2010trials\u2010in\u2010the\u2010uk\u2010the\u2010lord\u2010oshaughnessy\u2010review\u2010final\u2010report."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.26313"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae265"}],"container-title":["Developmental Medicine &amp; Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dmcn.16199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T13:14:35Z","timestamp":1748351675000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dmcn.16199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/dmcn.16199"],"URL":"https:\/\/doi.org\/10.1111\/dmcn.16199","archive":["Portico"],"relation":{},"ISSN":["0012-1622","1469-8749"],"issn-type":[{"value":"0012-1622","type":"print"},{"value":"1469-8749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]},"assertion":[{"value":"2024-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}