Tailored gene therapy dramatically reduces childhood epilepsy seizures in trial

An international team of researchers led by University of California San Diego and Rady Children's Institute for Genomic Medicine treated two children with SCN2A-related developmental epileptic encephalopathy using tailored gene therapy. The therapy, published on July 21, 2026 in Nature Medicine, resulted in a dramatic drop in seizure frequency for both patients over a two-year period. The nine-year-old patient experienced a 26% decrease in seizure frequency, while the 14-year-old patient had a 90% reduction, eventually reaching stretches of seizure-free days. Both patients showed developmental gains in language, motor skills, and adaptive behaviors, with reduced medication load and no serious side effects reported. Principal investigator Olivia Kim-McManus said the therapy is deliberately designed to target the individual's genetic diagnosis and modifies genetic expression and what proteins are expressed. The researchers created allele-selective antisense oligonucleotides that recognize harmless regions of DNA next to each child's disease-causing mutation. Injecting the ASOs under anesthesia directly into spinal fluid silenced the mutant version of the gene while allowing the other copy to function normally. The therapy was repeated every two to three months, with each child serving as their own control. Because the therapy affects gene expression but doesn't permanently change the underlying genetic code, it must be administered at regular intervals. During the trial, the older patient's ability to walk independently waned before the next dose, prompting researchers to adjust dosing frequency with FDA approval. Since then, he has been walking independently. Kim-McManus said these investigational therapies provide a model for rapidly translating personalized genetics into treatments for many other neurological and non-neurological diseases caused by single gene mutations.