Overview

• Using patient-derived induced pluripotent stem cells, researchers created 3D cortical and hippocampal assembloids to study DEE-13 caused by SCN8A variants.
• Cortical models showed hyperactive, seizure-like neuronal firing consistent with the disorder’s epileptic features.
• Hippocampal models displayed disrupted learning- and memory-related rhythms due to a selective loss of inhibitory neurons, supporting a direct cause for cognitive symptoms.
• Abnormal rhythms in the hippocampal assembloids matched patterns seen in patients’ seizure-prone hippocampal regions, validating the model against human data.
• Published in Cell Reports, the work establishes the first characterized human hippocampal assembloid platform with potential applications to autism, schizophrenia and Alzheimer’s research, though ongoing experiments have been halted by suspended NIH support.