DiscussionParkinson’s disease (PD) is a progressive neurodegenerative disorder that affects 1% of people over age 60 and more than five million people worldwide. PD research has been hindered by a lack of access to diseased tissue to study. However, with recent advances in stem cell biology, it is now possible to derive induced pluripotent stem cells (iPSCs) from control or PD patient fibroblasts and differentiate them into neurons. Concomitantly, there have been advances in gene editing technologies which now allow select mutations to be corrected or genes to be knocked out within iPSCs, resulting in pairs of cell lines with the same genetic background that differ by the presence or absence of specific disease-linked mutations or genes. Recently, Life Technologies has collaborated with the Parkinson’s Institute to develop PD model systems using donor fibroblasts collected at the Institute. We created a set of six iPSC lines from three PD patients (harboring PARK2, LRRK2 and/or GBA mutations), one MSA patient, and two age-matched controls. TALEN gene editing was utilized to correct mutations/knock out genes within two of the patient derived iPSC lines. All of the iPSC lines were differentiated into neural stem cells (NSCs). These NSCs were directly utilized in functional assays to compare their response to a number of different cellular stressors and were further differentiated into dopaminergic neurons. We will complete our disease modeling by using the pairs of isogenic lines generated in this study to assess functional differences between edited and unedited cells in fully differentiated dopaminergic neurons.