MAR 17, 2016 10:30 AM PDT

Promise and challenges of iPSC modeling in Parkinson's disease

Presented at: Neuroscience
Speaker
  • Associate Professor, Program Director of Gene Discovery and Stem Cell Modeling Parkinson's Institute and Clinical Center
    Biography
      Birgitt Schüle, MD, studied medicine at the Georg-August University, Göttingen and Medical University Lübeck, Germany from 1993-2001. She received her doctoral degree (Dr. med.) for her medical thesis in neurophysiology from the Georg-August University, Göttingen in 2001. Dr. Schüle worked during her neurological internship (2001-2002) at the Medical University Lübeck with Dr. Christine Klein on genetic forms of PD and dystonia. From 2003-2005, Dr. Schüle completed a postdoctoral fellowship in the laboratory of Dr. Uta Francke, Department of Genetics, Stanford University School of Medicine, before joining the Parkinson's Institute in October 2005.
      Dr. Schüle leads the genetics and biomarker program, since 2008, she has built a stem cell program developing novel "disease in-a-dish" models of Parkinson's disease using patient-derived induced pluripotent stem cells. In 2014, she became the director of the brain bank at the Parkinson's Institute.

    Abstract

    Given the challenges of replicating Parkinson’s disease in animal models, returning to models that are human-based and highly clinically characterized may provide the most successful path forward. There is a critical need to differentiate Lewy body Parkinson’s disease from other non-Lewy body forms of parkinsonism. This is important because the underlying molecular pathomechanisms, and hence potential therapeutic targets, are unlikely to be similar for both.
    One exciting new avenue regarding modeling human disease is the use of induced pluripotent stem cell (iPSC) technology utilizing individual donors with clear clinical diagnosis of disease. In regard to modeling Lewy body Parkinson’s disease, patient-specific iPSCs lay the foundation for differentiation into the tissue-type of interest, i.e. mid-brain dopaminergic neurons. Using such a collection of iPSCs that is thoroughly characterized with high-quality and comprehensive clinical data and eventually with confirmative neuropathology at autopsy is the key for successful interpretation of findings.
     
    However, in order for iPSC modeling approach to produce validated results, several challenges must be addressed to reduce variability of intrinsic and extrinsic nature. This is why it is critical that the methods used to generate iPSCs are documented and performed in a consistent manner to minimize variability. Another critical area for improvement is the use of consistent (or at least well documented) methods for differentiation of these patient-derived iPSC lines into neuronal cultures. The field is in dire need of standardized and validated iPS laboratory practices to generate and characterize cells and phenotypes of interest to understand disease and to identify new targets.
     
    Learning objectives:
    •           Clinical and pathological characterization of Lewy body Parkinson’s disease
    •           Critical factors of intrinsic and extrinsic variability for iPS cell modeling
     


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