Gene Technology Center


タイトル;Target specific drug screening using patient-derived induced pluripotent stem cell for methylmaronic acidemia..
発表者;松本 志郎 氏
(熊本大学 大学院生命科学研究部 小児科学分野)
High throughput screening (HTS) is needed for testing a large number of diverse chemical components, leading to identify possible components. HTS should be designed to be characterized by its simplicity, rapidness, low cost, and high efficiency. Recent studies revealed that patient-derived induced pluripotent stem cells (iPSCs) were useful for disease modeling and drug development and we established HTS using patient-iPSCs. Our targets is methylmaronic academia, which is a disorder of organic acid metabolism resulting from a functional defect of methylmalonyl-CoA mutase. MMA is associated with metabolic decompensation of whole body lead to significant morbidity and mortality. Especially, neurogenic complication is worst problem for unknown reason. Here we investigated disease-related phenotypes in human induced pluripotent stem cells(iPSCs), were collected from sever type of MMA patients of Mut0 (a male is 5 years old, a female is 4 years old and 3 years old female). We established HTS of fibroblast and neural progenitor cells (NPCs) derived from patient-iPSCs (Z-factor is 0.83 and 0.55 respectively). Large scale screening (1440 components) were tested in patients’ fibroblasts and Neural progenitor cells derived from patient-iPSCs. In this analysis, we identified 6 candidates with fibroblasts and 12 candidates with NPCs and all the candidates associated with signal-X pathway. Interestingly, only one component overlapped between fibroblasts and NPCs and the other 5 components in fibroblasts were not effective in 2nd screening tests. In this study, we demonstrated that target tissue derived from patient-iPSCs were effective tool for drug screening and pathophysiological understanding underling.

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