Project Abstract There are no animal models for sporadic forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) that account for over 90% of all patients. As the genetics of these diseases are not understood there are no drug targets to go for either. This proposal aims to use MPS devices to produce some of the first sporadic ALS and PD models of disease. Using patient specific induced pluripotent stem cells from rapidly progressing patients with early onset for maximal chance of seeing phenotypes, we will differentiate the cells into motor neurons or dopamine neurons – the two major cell types affected in the disease. Using cutting edge electrophysiology techniques and metabalomics combined with RNAseq and proteomic analysis we will establish solid biomarkers that define these two diseases when compared to healthy controls (UG3 phase). We will then develop novel MPS screens using the NCATS library of compounds based on the biomarkers discovered in the UH3 phase (UG3 phase). Together these studies will produce some of the first models of sporadic neurological disease using iPSC technology combined with MPS technology. Cedars-Sinai and the company Emulate have a 2 year relationship that forms the foundation of this proposal and an integrated institutional platform on which to collaborate to achieve the goals of the study.