Treatment of Rare Childhood Epilepsy Could Begin Before Birth

Featuring the work of CURE Epilepsy grantee Dr. Gemma Carvill

Research has shown that early diagnosis and treatment of epilepsy disorders can improve outcomes. A new study out of Northwestern University, authored by researchers including CURE Epilepsy grantee Dr. Gemma Carvill, suggests intervention to prevent epilepsy could start during pregnancy — as early as 15 weeks of gestation — well before symptoms appear, highlighting the potential benefit of treating certain epilepsy disorders as early as possible.

The study reveals for the first time how a novel RNA‑based treatment affects brain cell signaling when applied at early stages of development in a rare, severe, and treatment‑resistant form of epilepsy caused by changes in a gene called KCNT1. If given very early — possibly even in utero, or for preterm infants — the treatment may help protect the developing brain from hyper-excitation, and reduce long‑term neurological harm, the study found.

KCNT1-related epilepsy affects approximately 3,000 people worldwide. Children with KCNT1-associated epilepsy of infancy with migrating focal seizures (EIMFS) can have dozens or even hundreds of seizures a day, often don’t respond to standard treatments, and face a high risk of early death.

Using cells grown in the lab from children with a severe KCNT1 mutation, the scientists showed these cells produce excessive electrical activity, which helps explain why these children have seizures. The scientists then tested an experimental RNA-based therapy called an antisense oligonucleotide (ASO) aimed at reducing KCNT1 activity.

In the new study, the ASO successfully reduced the abnormal electrical currents in functional brain cells manufactured in the lab from patient cells. The scientists also tested the therapy in developing brain cells equivalent to the middle of pregnancy (15 to 21 weeks of gestation) and found it reduced excessive firing at this early stage, too. Although most genetic changes are present at conception, they might not be detectable or cause symptoms until later. Most routine prenatal tests can only detect large genetic changes while often missing single‑gene disorders like KCNT1‑related epilepsy.

The study found that adjusting the brain’s natural “cooldown” signal after a neuron fires (a process known as afterhyperpolarization) can meaningfully influence how brain cells behave. Future research aimed at understanding this cooling‑off process, particularly in living brains where neurons fire in complex patterns, could help scientists eventually treat a wide range of neurological disorders driven by overly excitable brain cells.

“The early brain is an amazingly plastic structure,” corresponding author Richard Smith said. “If we miss a therapeutic window, it becomes much harder to reverse the damage later as we manage symptoms in patients.”

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