AMBIGUOUS RESULTS

n-Lorem's personalized ASOs curb seizures in two SCN2A children

Nature Medicine detailed two single-patient trials of allele-selective antisense drugs, with no drug-related adverse events and functional gains in both children after more than two years of treatment.

Nature Medicine published results from two first-in-human, single-patient trials of allele-selective antisense oligonucleotides built for children with disease-causing SCN2A mutations, run by n-Lorem Foundation with investigators at UC San Diego, Rady Children's Institute for Genomic Medicine, and Rush University Medical Center.

By AppliedXLJuly 21, 2026Trial NCT06314490

Executive Summary

Two children with disease-causing SCN2A mutations who received custom-built, allele-selective antisense drugs showed reduced seizures and gains in motor and developmental function after extended treatment, with no drug-related safety signal.
Each child was the subject of a separate Phase 1/2, open-label, single-patient trial using a mutation-specific antisense oligonucleotide, a personalized-medicine model built for mutations too rare for a conventional drug program.
The result adds to a foundation's track record of treating nano-rare genetic disease with individualized antisense therapy, reinforcing that the approach can be delivered safely, though the evidence remains limited to single patients rather than a controlled cohort.
Because each trial enrolled exactly one patient with no comparator arm, the described improvements are clinical observations rather than statistically established treatment effects.

The publication

n-Lorem Foundation, a nonprofit that designs personalized antisense oligonucleotide (ASO) drugs for mutations found in as few as one to 30 people worldwide, said Nature Medicine published treatment results from two first-in-human, single-patient trials targeting pathogenic mutations in SCN2A, a gene that encodes an essential sodium channel. Each trial used a modified cross-over design and an allele-selective ASO, a drug engineered to suppress only the mutant copy of the gene while sparing the normal copy. The studies were run with principal investigators Olivia Kim-McManus at the University of California San Diego and Rady Children's Institute for Genomic Medicine, and Elizabeth Berry-Kravis at Rush University Medical Center. One of the two trials is registered as NCT06314490, a Phase 1/2, open-label study with a single enrolled patient that started February 16, 2024, and reached its primary completion date on February 16, 2026. Impressive+1

The design

SCN2A mutations are a recognized cause of severe early-life epilepsy, often producing uncontrolled seizures in infancy and lasting developmental impairment. Because these mutations occur in gain-of-function form, meaning the mutant protein disrupts normal channel activity rather than simply losing function, a therapy has to knock down the mutant copy while leaving the healthy copy intact. n-Lorem's allele-selective ASO platform is built to do that, and the company described it as the only technology that can routinely deliver this degree of mutation-specific selectivity. The registered trial's primary outcome measure was a gastrointestinal assessment using the Bristol Stool Chart, reflecting the autonomic and gut symptoms that accompany severe SCN2A disease. Impressive+1

The results

n-Lorem reported reductions in seizures, motor and developmental gains including newly independent walking, improved autistic symptoms in one child, and improved gastrointestinal and autonomic function in the other, after more than two years of treatment. No ASO-related adverse events or serious adverse events were reported in either patient. Stanley Crooke, n-Lorem's CEO, said the foundation is observing an excellent safety and tolerability profile across more than 50 patients treated with its personalized ASOs. Elizabeth Berry-Kravis said the data are reshaping expectations for neurodevelopmental disorders, since patients who began treatment with developmental impairment reached milestones some had not previously achieved. Impressive

How to weigh it

Each trial enrolled one patient, with the registered study showing actual enrollment of one against a target of one. That single-patient, open-label structure means the reported seizure reduction and developmental gains describe what happened in these two children rather than an effect measured against a placebo or an untreated comparator. The trial's registry history shows no protocol amendments since its 2024 initial posting, a stable record consistent with a single-patient study that did not need enrollment or eligibility changes. NCT06314490

The broader program

n-Lorem's pipeline record lists this SCN2A program as active and not recruiting, consistent with a personalized program that closes to enrollment once its one intended patient is dosed. The foundation is a nonprofit that builds a separate bespoke ASO for each patient's mutation rather than running a single trial meant to generalize across a patient population, so competitive or field-wide efficacy benchmarks for allele-selective ASOs in SCN2A disease do not apply in the way they would for a conventional multi-patient program. NCT06314490

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