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The sole treatment, cysteamine, slows down the disease progression, but does not correct the established renal proximal tubulopathy. Here, we developed a new therapeutic strategy by applying omics to expand our knowledge on the complexity of the disease and prioritize drug targets in cystinosis. We identified alpha\u2010ketoglutarate as a potential metabolite to bridge cystinosin loss to autophagy, apoptosis and kidney proximal tubule impairment in cystinosis. This insight combined with a drug screen revealed a bicalutamide\u2013cysteamine combination treatment as a novel dual\u2010target pharmacological approach for the phenotypical correction of cystinotic kidney proximal tubule cells, patient\u2010derived kidney tubuloids and cystinotic zebrafish.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202013067","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T06:00:41Z","timestamp":1624514441000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cysteamine\u2013bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5630-4159","authenticated-orcid":false,"given":"Amer","family":"Jamalpoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte AGH","family":"van Gelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fjodor A","family":"Yousef Yengej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther A","family":"Zaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sante P","family":"Berlingerio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koenraad R","family":"Veys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Pou Casellas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Voskuil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Essa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola ME","family":"Ammerlaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Rita","family":"Rega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-2846","authenticated-orcid":false,"given":"Reini EN","family":"van der Welle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R","family":"Lilien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten B","family":"Rookmaaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3077-5582","authenticated-orcid":false,"given":"Hans","family":"Clevers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-6228","authenticated-orcid":false,"given":"Judith","family":"Klumperman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Levtchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia R","family":"Berkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne C","family":"Verhaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-5945","authenticated-orcid":false,"given":"Maarten","family":"Altelaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1560-1074","authenticated-orcid":false,"given":"Rosalinde","family":"Masereeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-8096","authenticated-orcid":false,"given":"Manoe J","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"BFEMMM202013067_CR1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1097\/PAS.0b013e3181dc5e8a","volume":"34","author":"R Albadine","year":"2010","unstructured":"Albadine R, Schultz L, Illei P, Ertoy D, Hicks J, Sharma R, Epstein JI, Netto GJ (2010) PAX8 (+)\/p63 (\u2010) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. 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