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

ABSTRACT: Pyridoxine-dependent epilepsy (PDE) is a rare neurometabolic disorder of lysine catabolism caused by bi-allelic variants in ALDH7A1. This enzyme deficiency leads to accumulation of neurotoxic metabolites, pyridoxal-phosphate inactivation, and consequently severe neurological symptoms. Current treatments, including vitamin B6 supplementation and lysine-restricted diets, partially alleviate seizures and intellectual disability but are not curative. To explore underlying mechanisms and potential therapies, we generated patient-derived human induced pluripotent stem cell (hiPSC) lines that were subsequently differentiated into astrocytes, the primary source of ALDH7A1 in the brain and key regulators of metabolic homeostasis. Metabolomic analyses confirmed elevated PDE biomarkers,

SUBMITTER: Schuurmans IME 

PROVIDER: S-EPMC12554910 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature