Andres M Bratt-Leal, Thorsten Gorba, Roy M Williams, Jim A Mossman, Rachel Hills, Ha Tran, Derren Barken, Genevieve Beauvais, Daniel Fremgen, Ai Zhang, Cullen Pivaroff, Candace Lynch, Yanzheng Liu, Chandnee Chandrasekaran, David Tastad, Charlotte Bridge, Dustin R Wakeman, Uyen Nguyen, Brent Chamberlain, Emma L Lane, Mariah J Lelos, Jeanne F Loring, Edward D Wirth, Xiaokui Zhang
Toward development of an autologous, induced pluripotent stem cell (iPSC)-based cell therapy for Parkinson's disease (PD), we demonstrate successful, reproducible genomic and transcriptomic qualification of patient-derived dopaminergic neuron precursor cells (DANPCs) across multiple donors. Our analysis includes whole-genome sequencing data from fibroblasts, iPSCs, and DANPCs and the development of NeuriTest, an RNAseq-based bioinformatic analysis of DANPCs designed to predict cell quality based on empirical animal data. Autologous cell therapies are immune matched to the patient, potentially augmenting durability of benefit compared to allogeneic cells while negating the need for immunosuppression and accompanying side effects. Patient-specific iPSCs are an autologous cell source that can be differentiated to dopaminergic neurons, the cell type lost in PD. We report here our preclinical manufacturing strategy and results demonstrating efficacy in a PD rodent model and safety in a 9-month GLP toxicology study.