{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:17:11Z","timestamp":1778527031466,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["TR448\/11\u20101"],"award-info":[{"award-number":["TR448\/11\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SCHW416\/9\u20101"],"award-info":[{"award-number":["SCHW416\/9\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SCHW416\/5\u20102"],"award-info":[{"award-number":["SCHW416\/5\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["STR 1160\/1\u20102"],"award-info":[{"award-number":["STR 1160\/1\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>Incontinentia pigmenti<\/jats:italic> (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the <jats:italic>Nemo<\/jats:italic> gene. Replacing <jats:italic>Nemo<\/jats:italic> through gene therapy might provide therapeutic benefits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a mouse model of IP, we administered a single intravenous dose of the adeno\u2010associated virus (AAV) vector, AAV\u2010BR1\u2010CAG\u2010NEMO, delivering the <jats:italic>Nemo<\/jats:italic> gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood\u2013brain barrier (BBB) were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The endothelium\u2010targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV\u2010BR1\u2010CAG\u2010NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial\u2010targeted gene therapy in IP. Ann Neurol 2017;82:93\u2013104<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24981","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T15:32:41Z","timestamp":1497886361000},"page":"93-104","source":"Crossref","is-referenced-by-count":31,"title":["Gene therapy decreases seizures in a model of <i>Incontinentia pigmenti<\/i>"],"prefix":"10.1002","volume":"82","author":[{"given":"Godwin K.","family":"Dogbevia","sequence":"first","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"T\u00f6llner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine and Center for Systems Neuroscience Hannover 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L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacy University of Veterinary Medicine and Center for Systems Neuroscience Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology University of L\u00fcbeck L\u00fcbeck Germany"},{"name":"DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg\/L\u00fcbeck\/Kiel L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate K.","family":"Straub","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Center Mainz Mainz 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