Phenotypic drug screening and personalized medicine using patient-derived neuron models of SSADH

This project’s objective is to develop an in vitro disease model of SSADH Deficiency from patient iPSC linesdifferentiated into GABAergic neurons that will support phenotypic drug screening and personalized medicine.Our hypothesis posits that differentiation of human GABAergic neurons from SSADH patient derived iPSClines will exhibit some or all of the following biochemical and functional phenotypes 1) excessive GABA andGHB production; 2) impaired mitophagy and/or altered mTOR signaling secondary to the accumulation ofsupraphysiological [GABA]; 3) altered excitability or reduced dopaminergic transmission in mixed culturepreparations that contain both dopaminergic and GABAergic neurons. Furthermore, we anticipate that theseendpoints will be robustly expressed and suitable for assay development to support development of a mediumthroughput screen for therapeutic targets using the ArrayScan XTI High Content Screening platform housed inthe Human Neuron Core facility.