Research ArticleDIAMOND-BLACKFAN ANEMIA

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

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Science Translational Medicine  08 Feb 2017:
Vol. 9, Issue 376, eaah5645
DOI: 10.1126/scitranslmed.aah5645

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Inducing autophagy to improve anemia

Diamond-Blackfan anemia (DBA) is a rare blood disorder characterized by insufficient red blood cell production that is treated with corticosteroids and transfusion therapy. To identify additional therapeutics for DBA, Doulatov et al. performed a chemical screen with hematopoietic progenitor cells derived from iPSCs from two DBA patients with RPS19 and RPL5 genetic mutations. The autophagy inducing small-molecule SMER28 rescued erythroid differentiation in an autophagy factor ATG5-dependent manner in iPSC-derived patient cells, in zebrafish models of DBA, and in several mouse models. These results demonstrate the utility of iPSC-based screens for drug discovery for rare blood disorders and identify SMER28 and the autophagy pathway as promising targets for DBA therapy.

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