UCLA Researchers Find how Epilepsy Genes Disrupt Different Brain Regions using Stem Cell Models

This study was supported in part by a CURE Epilepsy award from CURE Epilepsy

A stem cell-based research study funded in part by CURE Epilepsy provided a step toward understanding why epilepsy caused by mutations in the SCN8A gene is difficult to treat, pointing to the distinct effects that single disease-causing gene variants can have across different regions of the brain.

The study focused on developmental and epileptic encephalopathy type 13, or DEE-13, which is caused by certain variants in the SCN8A gene. Children with DEE-13 experience frequent seizures as well as developmental delays, intellectual disability, and autism spectrum disorder.

Using patient-derived stem cells, the researchers generated advanced cellular models of two key brain areas: the cortex, which is essential for movement and higher-order thinking, and the hippocampus, which supports learning and memory.

The results revealed strikingly different effects depending on the brain region. In cortical models, the SCN8A variants made neurons hyperactive, mimicking seizure activity. However, in hippocampal models, the variants disrupted the brain rhythms associated with learning and memory. This disruption stemmed from a selective loss of specific hippocampal inhibitory neurons — the brain’s traffic cops that regulate neural activity.

While the study highlights a major advance in modeling human brain circuits, the researchers cautioned that continued progress depends on stable federal research support. “In my case, 100% of my NIH funding was suspended,” Samarasinghe said. “Without that support, we’ve had to halt experiments that took months to set up and put everything in the freezer, waiting to see if funding will return. Those kinds of disruptions make it incredibly difficult to move discoveries forward.”

Bennett Novitch, co-senior author, added that the stop-and-start funding climate has left labs caught between tremendous new capabilities and the inability to fully use them. “We’re able to create human brain-like specimens that finally allow us to probe the underlying causes of disease,” he said. “This is a goldmine for understanding epilepsy, autism, Alzheimer’s and other conditions — but we’re being impeded from taking advantage of what’s now technically possible.”

Both scientists stressed that the stakes go beyond academic progress. “Families come to us desperate for better options,” Samarasinghe said. “Without NIH funding, we can’t push forward the kinds of discoveries that could one day ease the daily struggles of children with epilepsy and related disorders. These delays don’t just set back science — they prolong suffering.”

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