Individualized ASOs Cut SCN2A Seizures by Up to 90%, Improve Development
Updated
Updated · Nature.com · Jul 23
Individualized ASOs Cut SCN2A Seizures by Up to 90%, Improve Development
2 articles · Updated · Nature.com · Jul 23
Summary
Two first-in-human n=1 studies in 9- and 14-year-old boys with SCN2A-related developmental epileptic encephalopathy found individualized allele-selective ASOs reduced seizures by 26% and 90% and improved neurodevelopment.
The therapy was designed to silence the mutant SCN2A transcript while preserving the healthy copy, a key consideration because SCN2A is dosage-sensitive and standard antiseizure drugs often fail.
Both patients had sustained seizure-free stretches, needed fewer concomitant medications, and had no seizure-related ER visits or hospitalizations after treatment; neither had ASO-related serious adverse events.
Patient 2 also gained independent gait at age 15 and showed improved communication and bowel function, while Patient 1 improved in language, motor skills and autistic behaviors.
A separate rapid-genomics cohort found 16% of SCN2A-related cases carried compatible SNP configurations, suggesting these individualized drugs could be extended from n=1 to more monogenic-disease patients.