{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:20:50Z","timestamp":1784164850666,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vivet Therapeutics SAS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder caused by mutations in the gene encoding argininosuccinate synthetase 1 (ASS1) that catalyzes the third step of the urea cycle. CTLN1 patients suffer from impaired elimination of nitrogen, which leads to neurotoxic levels of circulating ammonia and urea cycle byproducts that may cause severe metabolic encephalopathy, death or irreversible brain damage. Standard of care (SOC) of CTLN1 consists of daily nitrogen-scavenger administration, but patients remain at risk of life-threatening decompensations. We evaluated the therapeutic efficacy of a recombinant adeno-associated viral vector carrying the ASS1 gene under the control of a liver-specific promoter (VTX-804). When administered to three-week-old CTLN1 mice, all the animals receiving VTX-804 in combination with SOC gained body weight normally, presented with a normalization of ammonia and reduction of citrulline levels in circulation, and 100% survived for 7 months. Similar to what has been observed in CTLN1 patients, CTLN1 mice showed several behavioral abnormalities such as anxiety, reduced welfare and impairment of innate behavior. Importantly, all clinical alterations were notably improved after treatment with VTX-804. This study demonstrates the potential of VTX-804 gene therapy for future clinical translation to CTLN1 patients.<\/jats:p>","DOI":"10.3390\/ijms232314940","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T01:52:20Z","timestamp":1669773140000},"page":"14940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8275-337X","authenticated-orcid":false,"given":"Andrea","family":"Bazo","sequence":"first","affiliation":[{"name":"Division of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-9895","authenticated-orcid":false,"given":"Aquilino","family":"Lantero","sequence":"additional","affiliation":[{"name":"Vivet Therapeutics, S.L., 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsaso","family":"Maule\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire","family":"Neri","sequence":"additional","affiliation":[{"name":"Vivet Therapeutics, S.L., 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-314X","authenticated-orcid":false,"given":"Martin","family":"Poms","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, University Children\u2019s Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Children\u2019s Research Centre (CRC), University Children\u2019s Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ricobaraza","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-0926","authenticated-orcid":false,"given":"Bernard","family":"B\u00e9nichou","sequence":"additional","affiliation":[{"name":"Vivet Therapeutics, S.A.S., 75008 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Combal","sequence":"additional","affiliation":[{"name":"Vivet Therapeutics, S.A.S., 75008 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-4562","authenticated-orcid":false,"given":"Gloria","family":"Gonzalez-Aseguinolaza","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra, 31008 Pamplona, Spain"},{"name":"Vivet Therapeutics, S.L., 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Aldabe","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy and Regulation of Gene Expression, CIMA, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2791S","DOI":"10.1093\/jn\/134.10.2791S","article-title":"Arginine Metabolism: Enzymology, Nutrition, and Clinical Significance","volume":"134","author":"Brosnan","year":"2004","journal-title":"J. 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