Rare metabolic disorders such as pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type I (GA1) cause severe epilepsy and permanent brain damage in young children. Effective treatments are largely lacking. This research developed patient-specific brain cell models and a new, efficient way to generate these brain cells. This allowed the diseases to be accurately modelled and provided better insight into how toxic metabolies accumulate and disrupt brain cell function. In addition, a novel therapeutic strategy was tested that partially slows the breakdown of lysine, an amino acid. This reduced toxic metabolites and restored key brain cell functions, pointing to a potential shared treatment for multiple lysine metabolism disorders. The study also shows that lysine itself plays an active role in communication between brain cells. These insights open new avenues for understanding and treating rare brain disorders.
Imke Schuurmans obtained her bachelor’s degree in Biology and Medical Laboratory Research at the HAN and her master’s degree in Biomedical Sciences at Radboud University. In 2020, she started her PhD at the Department of Pediatrics at Radboudumc. She is currently working at the Genetics department, focussing on rare genetic (and metabolic) epilepsies using brain models and tests novel therapies.