Personalized gene therapy helps teen with epilepsy walk independently

Researchers at UC San Diego and Rady Children's Institute for Genomic Medicine have demonstrated that personalized gene therapy tailored to individual genetic mutations can dramatically reduce seizures and unlock developmental milestones in children with a severe form of epilepsy. The results, published on July 21, 2026, in Nature Medicine, showed that a 14-year-old patient achieved a 90% reduction in seizure frequency and walked independently for the first time at age 15.miragenews+1

A Therapy Designed for One

SCN2A-related developmental epileptic encephalopathy is a rare condition caused by spontaneous mutations to the SCN2A gene, which controls sodium ion flow into neurons. Traditional anti-seizure medications are often ineffective because they fail to address the underlying genetic cause.miragenews

The international team, led by principal investigator Olivia Kim-McManus, created short synthetic DNA molecules called allele-selective antisense oligonucleotides, or ASOs, designed to recognize and silence each child's specific disease-causing mutation while leaving the functional copy of the gene intact. The ASOs were injected directly into spinal fluid under anesthesia every two to three months across two separate n-of-1 clinical trials lasting two years.miragenews

"The therapy is deliberately designed to target the individual's genetic diagnosis," said Kim-McManus, associate professor of neurosciences at UC San Diego School of Medicine and director of the Rady Precision Therapeutics Neuro-Interventional Program.miragenews

Two Patients, Broad Gains

The two children enrolled were aged nine and 14 at the start of the trials. The younger patient, who previously seized nearly every day, experienced a 26% drop in seizure frequency. The older patient saw a 90% reduction, eventually reaching stretches of seizure-free days. Both patients were able to reduce or stop some anti-seizure medications and showed improvements in language, motor skills, sensory processing, and adaptive behaviors, with a reduction in autism-related behaviors.miragenews

No serious side effects or ASO-related adverse events were reported during the two-year period.insideprecisionmedicine+1

Because the therapy modifies gene expression without permanently altering genetic code, it requires repeated dosing. When the older patient's ability to walk independently began to wane before his next scheduled dose, the researchers adjusted the frequency with FDA approval. "Since then, he's been walking independently," Kim-McManus said.miragenews

A Model for Precision Medicine

The study involved collaborators from Ionis Pharmaceuticals ↘ 2.49%, the n-Lorem Foundation, Rush University Medical Center, Boston Children's Hospital, and the University of Melbourne, and was funded in part by the California Institute for Regenerative Medicine.miragenews

Kim-McManus said the approach could serve as a model for rapidly translating personalized genetics into treatments for many other diseases caused by single-gene mutations. "It's like a sci-fi, Star Trek idea," she said. "But now that we're on the other side showing safety and efficacy, the idea is spreading beyond academia to the pharma and biotech industry."miragenews