{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:26:43Z","timestamp":1767911203358,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005674","name":"Cystinosis Research Foundation","doi-asserted-by":"publisher","award":["#CRFS-2014"],"award-info":[{"award-number":["#CRFS-2014"]}],"id":[{"id":"10.13039\/100005674","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health","award":["#RC2015"],"award-info":[{"award-number":["#RC2015"]}]},{"name":"E-rare European Union","award":["#E-Rare-2 JCT 2014"],"award-info":[{"award-number":["#E-Rare-2 JCT 2014"]}]},{"name":"Foundation of Scientific Research Flanders","award":["#11Y5216N"],"award-info":[{"award-number":["#11Y5216N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nephropathic cystinosis is a rare disease caused by mutations of the CTNS gene that encodes for cystinosin, a lysosomal cystine\/H+ symporter. The disease is characterized by early-onset chronic kidney failure and progressive development of extra-renal complications related to cystine accumulation in all tissues. At the cellular level, several alterations have been demonstrated, including enhanced apoptosis, altered autophagy, defective intracellular trafficking, and cell oxidation, among others. Current therapy with cysteamine only partially reverts some of these changes, highlighting the need to develop additional treatments. Among compounds that were identified in a previous drug-repositioning study, disulfiram (DSF) was selected for in vivo studies. The cystine depleting and anti-apoptotic properties of DSF were confirmed by secondary in vitro assays and after treating Ctns-\/- mice with 200 mg\/kg\/day of DSF for 3 months. However, at this dosage, growth impairment was observed. Long-term treatment with a lower dose (100 mg\/kg\/day) did not inhibit growth, but failed to reduce cystine accumulation, caused premature death, and did not prevent the development of renal lesions. In addition, DSF also caused adverse effects in cystinotic zebrafish larvae. DSF toxicity was significantly more pronounced in Ctns-\/- mice and zebrafish compared to wild-type animals, suggesting higher cell toxicity of DSF in cystinotic cells.<\/jats:p>","DOI":"10.3390\/cells10123294","type":"journal-article","created":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T22:19:16Z","timestamp":1638137956000},"page":"3294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Benefits and Toxicity of Disulfiram in Preclinical Models of Nephropathic Cystinosis"],"prefix":"10.3390","volume":"10","author":[{"given":"Anna","family":"Taranta","sequence":"first","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3154-1948","authenticated-orcid":false,"given":"Mohamed A.","family":"Elmonem","sequence":"additional","affiliation":[{"name":"Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo 11956, Egypt"},{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-8764","authenticated-orcid":false,"given":"Francesco","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"De Leo","sequence":"additional","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Boenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry Unit, Department of Pediatric Medicine, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoe J.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amer","family":"Jamalpoor","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura R.","family":"Rega","sequence":"additional","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-6594","authenticated-orcid":false,"given":"Isabella","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"Department of Pathology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-2383","authenticated-orcid":false,"given":"Paola","family":"Francalanci","sequence":"additional","affiliation":[{"name":"Department of Pathology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambertus P.","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Pediatric Nephrology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Dionisi-Vici","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry Unit, Department of Pediatric Medicine, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca M.","family":"Goffredo","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry Unit, Department of Pediatric Medicine, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-1074","authenticated-orcid":false,"given":"Rosalinde","family":"Masereeuw","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7312","authenticated-orcid":false,"given":"Elena","family":"Levtchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"},{"name":"Division of Pediatric Nephrology, Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Emma","sequence":"additional","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare 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