{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:39:18Z","timestamp":1791272358555,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T00:00:00Z","timestamp":1393977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies.<\/jats:p>","DOI":"10.5966\/sctm.2013-0168","type":"journal-article","created":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T05:40:04Z","timestamp":1394084404000},"page":"510-519","source":"Crossref","is-referenced-by-count":49,"title":["Induced Pluripotent Stem Cells Reveal Functional Differences Between Drugs Currently Investigated in Patients With Hutchinson-Gilford Progeria Syndrome"],"prefix":"10.1093","volume":"3","author":[{"given":"Sophie","family":"Blondel","sequence":"first","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laure","family":"Jaskowiak","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Cellules Souches, Institut for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Fran\u00e7aise Contre les Myopathies, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laure","family":"Egesipe","sequence":"additional","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Le Corf","sequence":"additional","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Navarro","sequence":"additional","affiliation":[{"name":"INSERM-Aix-Marseille Universit\u00e9 Unit\u00e9 Mixte de Recherche S 910 G\u00e9n\u00e9tique M\u00e9dicale et G\u00e9nomique Fonctionnelle, Facult\u00e9 de M\u00e9decine Timone, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Cordette","sequence":"additional","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Martinat","sequence":"additional","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacine","family":"Laabi","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Cellules Souches, Institut for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Fran\u00e7aise Contre les Myopathies, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Djabali","sequence":"additional","affiliation":[{"name":"Department of Dermatology and IMETUM, Technische Universitat Munchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annachiara","family":"de Sandre-Giovannoli","sequence":"additional","affiliation":[{"name":"INSERM-Aix-Marseille Universit\u00e9 Unit\u00e9 Mixte de Recherche S 910 G\u00e9n\u00e9tique M\u00e9dicale et G\u00e9nomique Fonctionnelle, Facult\u00e9 de M\u00e9decine Timone, Marseille, France"},{"name":"AP-HM D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital d'Enfants, Timone, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Levy","sequence":"additional","affiliation":[{"name":"INSERM-Aix-Marseille Universit\u00e9 Unit\u00e9 Mixte de Recherche S 910 G\u00e9n\u00e9tique M\u00e9dicale et G\u00e9nomique Fonctionnelle, Facult\u00e9 de M\u00e9decine Timone, Marseille, France"},{"name":"AP-HM D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital d'Enfants, Timone, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Peschanski","sequence":"additional","affiliation":[{"name":"INSERM\/Universit\u00e9 Evry Val d'Essonne 861, Evry, France"},{"name":"Centre d'Etude des Cellules Souches, Institut for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Fran\u00e7aise Contre les Myopathies, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Nissan","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Cellules Souches, Institut for Stem Cell Therapy and Exploration of Monogenic Diseases, Association Fran\u00e7aise Contre les Myopathies, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry, 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