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CADASIL is caused by mutations in the\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    gene, resulting in a mutated NOTCH3 receptor, with aggregation of the NOTCH3 extracellular domain (ECD) around vascular smooth muscle cells. In this study, we have developed a novel active immunization therapy specifically targeting CADASIL\u2010like aggregated NOTCH3 ECD. Immunizing CADASIL TgN3R182C\n                    <jats:sup>150<\/jats:sup>\n                    mice with aggregates composed of CADASIL\u2010R133C mutated and wild\u2010type EGF\n                    <jats:sub>1\u20135<\/jats:sub>\n                    repeats for a total of 4\u2009months resulted in a marked reduction (38\u201348%) in NOTCH3 deposition around brain capillaries, increased microglia activation and lowered serum levels of NOTCH3 ECD. Active immunization did not impact body weight, general behavior, the number and integrity of vascular smooth muscle cells in the retina, neuronal survival, or inflammation or the renal system, suggesting that the therapy is tolerable. This is the first therapeutic study reporting a successful reduction of NOTCH3 accumulation in a CADASIL mouse model supporting further development towards clinical application for the benefit of CADASIL patients.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202216556","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T03:36:56Z","timestamp":1671161816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Active immunotherapy reduces NOTCH3 deposition in brain capillaries in a CADASIL mouse model"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-2934","authenticated-orcid":false,"given":"Daniel V","family":"Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-1043","authenticated-orcid":false,"given":"Kirsten G","family":"Coupland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9064-9246","authenticated-orcid":false,"given":"Shaobo","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-1377","authenticated-orcid":false,"given":"Francesca","family":"Del Gaudio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhys","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie W","family":"Rutten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Sandin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Lundkvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-8995","authenticated-orcid":false,"given":"Saskia AJ","family":"Lesnik Oberstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9543-8141","authenticated-orcid":false,"given":"Urban","family":"Lendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0498-2473","authenticated-orcid":false,"given":"Helena","family":"Karlstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"BFEMMM202216556_CR1","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2019.104504","volume":"130","author":"M Alpaugh","year":"2019","unstructured":"Alpaugh M, Cicchetti F (2019) A brief history of antibody\u2010based therapy. 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