Development of a suite of assays for the analysis of PWS patient iPSC-derived cortical neurons

Funding Summary

Dr. Bang and her team will use PWS patient-specific induced pluripotent stem cells (iPSC) to address a major gap- the absence of human cell-based systems that can be used to discover novel therapeutic targets, screen for drugs, and test drugs in patient and disease relevant contexts. They will employ a suite of assays to assess PWS patient versus control iPSC-derived cortical cells to monitor differentiation and to assay neuronal networks. Once these PWS phenotypic assays have been validated, they can be used to identify molecular targets and to screen for and test drug candidates.

Lay Abstract

Although early diagnosis, dietary interventions and hormone treatments can improve prognoses, PWS patients are greatly in need of more therapeutic options. In this proposal we will use PWS patient-specific induced pluripotent stem cells (iPSC) to address a major gap- the absence of human cell-based systems that can be used to discover novel therapeutic targets, screen for drugs, and test drugs in patient and disease relevant contexts. Importantly, for modeling such a genetically complex disease, iPSC have the advantage of reflecting patient genetics, both the PWS critical region, and the complex individual genetic backgrounds that likely impact the spectrum of phenotypic severities characterizing PWS. We will focus our efforts on PWS patient iPSC-derived cortical neural populations, with the longer-term goal of investigating the underlying cellular bases of PWS associated behavioral and psychiatric symptoms. We will employ a suite of assays we developed in higher throughput formats to assess PWS patient versus control iPSC-derived cortical cells to first monitor differentiation using high content imaging, and second, to assay neuronal networks using multi-electrode arrays. These efforts will lay the groundwork for future studies that will include a broader representation of PWS genetic lesions, and other disease relevant cell types such as hypothalamic neurons. Once PWS phenotypic assays have been validated, they can be employed in drug discovery efforts, to identify molecular targets and to screen for and test drug candidates.

Funded Year:

2020

Awarded to:

Anne Bang, Ph.D

Amount:

$81,037

Institution:

Sanford Burnham Prebys Medical Discovery Institute

Researcher:

Anne Bang, Ph.D

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