Genomic and Transcriptomic Quality Control for an Autologous iPSC-Derived Cell Therapy for Parkinson’s Disease

This is a multimodal study, integrating RNAseq, whole genome sequencing (WGS), and microarray data to support the development and validation of a novel autologous iPSC-derived dopaminergic neuron therapy for Parkinson’s disease (PD). In this study, we present preclinical data and our manufacturing strategy for developing an autologous iPSC-derived dopaminergic neuron therapy for PD. Our approach addresses prior safety concerns by implementing whole genome sequencing at multiple stages of iPSC derivation and differentiation. To address the challenge of reproducibly qualifying individual cultures of DANPCs for optimal efficacy (Jeon, Cha et al. 2025), we developed a novel transcriptomic assay, “NeuriTest”, which identifies the optimal differentiation stage for engraftment and efficacy. Using the PluriTest model (Muller, Schuldt et al. 2011), NeuriTest was created by generating a reference database of gene expression profiles and using machine learning to identify profiles that correlate with efficacy. In contrast to scale-up processes used for allogeneic products, we employ a cost-effective fail-fast manufacturing paradigm that identifies quality control failures early in the process. The data reported here underpin the launch of ASPIRO, the first multicenter Phase 1/2a clinical trial of autologous iPSC-derived dopaminergic neuron replacement for PD (ClinicalTrials.gov ID: NCT06344026), with initial dosing completed in 2024. This data supports the genomics quality control metrics we developed to support this novel personalized therapeutic approach.

• Type: RNASeq
• Archive: European Genome-phenome Archive (EGA)