Personalized ASOs were developed for two children with SCN2A epilepsy; in an open-label study, seizure frequency fell by 90% in the older child
Drugs tailored to the mutations of two boys with severe genetic epilepsy were developed; in an open-label study, seizure frequency fell by 90% in one child
On 21 July 2026, Nature Medicine published a report on two separate studies involving a nine-year-old boy and a 14-year-old boy with epilepsy caused by SCN2A mutations. Each boy received a different antisense oligonucleotide (ASO). These short molecules bind to RNA, which carries the instructions that cells use to make proteins, and help the cell destroy it.
The SCN2A gene encodes the NaV1.2 sodium channel, which neurons use to conduct electrical signals. In the younger boy, the mutation made the channel overactive. In the older boy, the mutation both increased and reduced its activity. In both children, the disease caused severe seizures beginning early in life and arrested development.
Each cell contains two copies of SCN2A. Suppressing both could cause a different problem because reduced activity of both copies is associated with autism and developmental delay. The ASO therefore had to reduce the activity of only the mutated copy without affecting the healthy copy.
The team identified a harmless genetic marker near the mutation that distinguished the affected copy of the gene from the healthy one. The drug binds to RNA produced from that copy, causing the cell to destroy it. In the patients' cells, it suppressed the mutant RNA tens of times more strongly than RNA from the healthy copy.
The younger boy received 12 doses over two years. His seizure frequency decreased by 26%, but this change could have reflected normal variation. The older boy received eight doses over 16 months. His motor seizures fell from two per day to none by month 14; a statistical model specified before the study began estimated a 90% reduction. At 15, he began walking independently for the first time. Both boys were able to reduce their antiseizure medications, and the authors recorded no serious adverse effects related to the ASO.
Doctors administer the ASO into the cerebrospinal fluid every 60–90 days. The DNA remains unchanged because the drug only temporarily reduces the amount of RNA. In the older boy, seizures began increasing again about 60 days after each dose, so the doctors shortened the interval between doses.
The same ASO could be suitable for another child if the mutation affects SCN2A function in the same way and the same genetic marker is present nearby. Among 19 children with this disease, three had this combination; they were not treated with this drug.
Each study involved one child and had no comparison group. These results describe two individual cases. Whether they can be reproduced in children with other SCN2A variants can be determined only through further studies.