Targeting AASS improves neurotoxicity and mitochondrial function in astrocyte models for pyridoxine dependent epilepsy

Pyridoxine-dependent epilepsy (PDE) is a rare neurometabolic disorder of lysine catabolism, which is caused by pathogenic variants in ALDH7A1. In this study, we performed RNA sequencing on differentiated astrocytes derived from patient and isogenic knock-out iPSC lines. We identified a reduced expression of genes associated with oxygen response, which correlates with heightened oxidative stress in PDE astrocytes. Overall design: Transcriptomic profiling of human iPSC-derived astrocytes was performed using two control lines (C1, C4), two Pyridoxine-dependent epilepsy (PDE) patient lines (P1, P3), and an isogenic ALDH7A1-/- line derived from C1. Each cell line included three biological replicates.