UCLA scientists used patient-derived induced pluripotent stem cells to build 3D “assembloid” models of cortex and hippocampus for DEE-13, a rare SCN8A-related childhood epilepsy. The same SCN8A variants produced region-specific effects: cortical assembloids showed seizure-like hyperexcitability, while hippocampal assembloids lost key inhibitory neurons and displayed disrupted learning- and memory-related rhythms. This helps explain why seizure control alone often fails to address cognitive, behavioral, and sleep problems. The work establishes the first human hippocampal assembloid that reproduces abnormal activity seen in patients.
Validating the model with patient hippocampal recordings, researchers observed matching abnormal rhythms in seizure-prone regions and in SCN8A-variant assembloids, while controls appeared normal. Beyond epilepsy, the platform enables mechanistic studies and therapy testing for conditions involving hippocampal circuits (eg, autism, schizophrenia, Alzheimer’s disease). The team also emphasized the need for stable federal support to sustain and extend this translational work, which was funded by the National Institutes of Health and several foundations.
Reference: Dunlap T. UCLA researchers find how epilepsy genes disrupt different brain regions using stem cell models. UCLA. Published September 8, 2025. Accessed September 16, 2025. https://newsroom.ucla.edu/releases/epilepsy-genes-disrupt-brain-regions-stem-cell-model-ucla-research-discovery
