They rewrote a single letter of his DNA—and a teenager who never walked took his first steps. What if the real cure was hiding in plain sight?
New Hope for SCN2A-Related Developmental Epileptic Encephalopathy
A teenager who once could not walk now strides independently. How? A two-year treatment that targets the genetic root of epilepsy changed everything. The therapy dramatically reduced seizures and unlocked developmental gains in two children with SCN2A-related developmental epileptic encephalopathy (DEE).
For children with this rare childhood epilepsy, seizures begin early. Serious delays in movement, communication, and other abilities often follow. The disorder is also one of the most common causes of autism linked to a single-gene mutation. But what exactly goes wrong?
The SCN2A Mutation: What Causes the Brain to Become Overexcitable?
The SCN2A gene encodes a sodium voltage-gated channel alpha subunit. This protein regulates sodium ion movement into neurons. When a mutation strikes, brain cells become abnormally excitable. Uncontrolled seizures, developmental delays, autism, movement difficulties, and gastrointestinal problems then emerge. Most mutations arise de novo—they occur spontaneously, not inherited from a parent.
Standard anti-seizure medications offer limited relief. Why? They fail to correct the underlying genetic mechanism. An international team led by the University of California San Diego and Rady Children’s Institute for Genomic Medicine therefore developed a different approach. They created treatments matched to each child’s specific SCN2A mutation.
Personalized ASO Therapy: Silencing the Faulty Gene Copy
People carry two copies of each gene. SCN2A mutations typically affect only one copy. The researchers designed short synthetic DNA strands called allele-selective antisense oligonucleotides (ASOs). Each ASO recognized a harmless stretch of genetic material next to the disease-causing mutation.
“The therapy is deliberately designed to target the individual’s genetic diagnosis,” said principal investigator Olivia Kim-McManus, MD, associate professor of neurosciences at UC San Diego School of Medicine. She is also director of the Rady Precision Therapeutics Neuro-Interventional Program at Rady Children’s Hospital San Diego and a clinical investigator at Rady Children’s Institute for Genomic Medicine. “The ASO modifies genetic expression and what proteins are expressed.”
Doctors delivered the ASOs directly into the spinal fluid while each child was under anesthesia. The treatment suppressed activity from the mutated SCN2A copy. Meanwhile, the unaffected copy continued to function normally.
Seizure Frequency Decline: Twenty-Six Percent and Ninety Percent Reductions
Each child received another dose every two to three months. They served as their own control. Researchers compared seizure frequency, medication use, development, and behavior before and after treatment. After two years, the results were striking.
The nine-year-old patient previously experienced seizures almost every day. After treatment, seizure frequency dropped by twenty-six percent. The fourteen-year-old patient achieved a ninety percent reduction. Eventually, he experienced periods of seizure-free days.
Both children reduced or discontinued some anti-seizure medications. But the benefits went beyond seizures.
Developmental Gains: Walking Independently for the First Time at Age Fifteen
Language, motor abilities, sensory processing, and adaptive behavior all improved. Autism-related behaviors decreased. Most remarkably, at age fifteen, the older patient walked independently for the first time. His long-standing gastrointestinal problems also improved, reducing the need for medication.
Researchers reported no serious side effects or adverse events linked to the ASOs. Routine laboratory testing, electrocardiograms, and electroencephalograms remained stable.
“We’ve seen changes across the board, showing that targeting the root genetic cause can produce measurable improvement,” said Kim-McManus.
Repeated Dosing: Why the Treatment Requires Continual Care
The therapy changes how the gene is expressed. It does not permanently rewrite the genetic code. Regular doses are therefore necessary. During the trial, the older patient began losing some walking ability as the next scheduled treatment approached. With FDA approval, researchers shortened the interval between doses.
“Since then, he’s been walking independently,” said Kim-McManus. “When we really think about precision therapy in a personalized way, you can’t get more personalized than that.”
A Model for Personalized Genetic Medicine: What Does the Future Hold?
Kim-McManus cautioned that the treatments remain investigational. Even so, these studies demonstrate how an individual genetic diagnosis can be rapidly translated into a personalized therapy. The same approach could potentially speed treatment development for other neurological and non-neurological conditions caused by single-gene mutations.
“It’s like a sci-fi, Star Trek idea, and that’s the look that I used to get when I was just starting this,” said Kim-McManus. “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 and having a big impact.”
What does this mean for families waiting for a cure? Could this n-of-one framework become a standard path for rare genetic diseases? The answer may lie in more trials, more partnerships, and more children who take their first independent steps.
Source: They rewrote a single letter of his DNA—and a teenager who never walked took his first steps. What if the real cure was hiding in plain sight?
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They rewrote a single letter of his DNA—and a teenager who never walked took his first steps. What if the real cure was hiding in plain sight?
Sources:
- Kim-McManus, O., et al. (2025). Personalized antisense oligonucleotide therapy for SCN2A-related developmental epileptic encephalopathy. Nature Medicine.
- University of California San Diego. (2025). Teen Walks Independently After Treatment Targets the Genetic Root of Epilepsy. Press release.
- Rady Children’s Institute for Genomic Medicine. (2025). Precision Therapeutics Neuro-Interventional Program.