Dr. Bang and her team will apply a series of ‘assays’ (lab tests evaluating cell function) to PWS patient-specific stem cells (iPSC) that have been driven to become cortical neurons in a lab dish. Once validated, these assays can be used to discover novel therapeutic targets for PWS, screen for drugs that can correct impaired neuronal function, and test drugs in a PWS- relevant context.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Watch the full webinar describing all 7 research projects funded in this grant cycle here.
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.
Anne Bang, Ph.D
Sanford Burnham Prebys Medical Discovery Institute
Anne Bang, Ph.D