{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T18:05:28Z","timestamp":1771956328587,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T00:00:00Z","timestamp":1588982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Italian Ministry of Health","award":["RC 7_2014"],"award-info":[{"award-number":["RC 7_2014"]}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>Ataxia telangiectasia (AT) and Aicardi\u2013Gouti\u00e8res syndrome (AGS) are inherited disorders of immunity with prevalent neurological phenotype. Available treatments are only partially effective, and the prognosis is poor. Induced pluripotent stem cells (iPSCs) are obtained by reprogramming patient somatic cells, preserving the donor individual genetic heritage and creating patient\u2010specific disease models, useful to investigate pathogenesis and drug effects and to develop precision therapies. The aim is to investigate the cytotoxicity of a panel of immunomodulators using iPSCs of patients with AT or different forms of AGS (AGS1, AGS2, and AGS7). iPSCs were obtained by reprogramming AT and AGS patients\u2019 cells and, as a control, the BJ normal human fibroblast line, using Sendai virus. Cytotoxic effects of two drugs proposed to treat respectively AT and AGS (dexamethasone and mepacrine) were tested by the 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide assay after 72\u00a0hours' exposure. Data were obtained also for other immunomodulatory drugs (thioguanine, mercaptopurine, thalidomide, and lenalidomide). Relative expression of genes involved in the tested drug pathways was analyzed. AGS7\u2010derived iPSCs displayed altered viability when treated with a low dose of mepacrine and higher expression of cyclic guanosine monophosphate\u2013adenosine monophosphate synthase, which is the main target for mepacrine action. AGS7\u2010derived iPSCs were also more sensitive to thioguanine, while AGS2 and AT iPSCs were less sensitive to this medication than the BJ\u2010iPSC. All iPSCs were equally sensitive to mercaptopurine and resistant to dexamethasone, thalidomide, and lenalidomide. This work establishes an innovative <jats:italic>in vitro<\/jats:italic> model that is useful to investigate the mechanisms of drugs potentially effective in AT and AGS.<\/jats:p>","DOI":"10.1002\/cpt.1837","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T16:23:15Z","timestamp":1585930995000},"page":"358-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biomarkers and Precision Therapy for Primary Immunodeficiencies: An <i>In Vitro<\/i> Study Based on Induced Pluripotent Stem Cells From Patients"],"prefix":"10.1111","volume":"108","author":[{"given":"Elena","family":"Genova","sequence":"first","affiliation":[{"name":"PhD Course in Reproductive and Developmental Sciences University of Trieste Trieste Italy"},{"name":"Department of Life Sciences University of Trieste Trieste 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