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iPSC-derived neural cells for drug discovery of mitochondrial brain diseases

Speaker
  • Independent Team Leader, Max Delbrueck Center for Molecular Medicine (MDC)
    Biography
      Dr. Prigione is an Independent Team Leader at the Max Delbrueck Center for Molecular Medicine (MDC) in Berlin. His group was established in 2015 with the generous support of a junior investigator grant from the German Ministry of Education and Research (BMBF).
      Dr. Prigione received a M.D. from the University of Milan in 2002 and a Ph.D. from the San Raffaele Institute of Milan in 2008. During his Ph.D., Dr. Prigione worked on neurological diseases at the University of Milan-Bicocca and on mitochondrial disorders at the University of California in Davis, USA. As postdoctoral scientist at the Max Planck Institute for Molecular Genetics in Berlin, Dr. Prigione described for the first time the reconfiguration occurring to mitochondria during the reprogramming of human fibroblasts to iPSCs.
      The focus of the Prigione lab is now the application of iPSCs in modeling and treatment discovery of neurological diseases with mitochondrial impairment. His latest work was published in Cell Stem Cell in January 2017 and demonstrated the use of iPSC-derived neural cells for drug discovery of neurological disorders caused by mitochondrial DNA mutations.

    Abstract

    Mitochondrial defects represent a common pathogenetic mechanism associated with neurodegeneration. At the same time, mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Addressing the mechanisms underlying mitochondrial impairment in patient-derived neural cells may therefore lead to the identification of therapeutic strategies counteracting neurodegeneration.

    A critical element for cell-based drug discovery is the use of cells that are homogeneous and obtainable in a reproducible manner. We recently showed that NPCs derived from human induced pluripotent stem cells (iPSCs) represent an effective model system for mtDNA disease drug discovery (Lorenz et al, Cell Stem Cell 2017). Here, we present how we derive NPCs and post-mitotic neurons in a robust manner in order to use these cells for therapeutic screenings. Finally, we describe how to analyze the mitochondrial and metabolic properties of the patient-derived cells and how to set up high-content analysis (HCA)-based compound screening strategies.

     


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