Allele-Specific Antisense Therapy Reduces Seizures in SCN2A-Linked Epilepsy

Researchers report that allele-specific antisense oligonucleotides targeting faulty SCN2A mRNA in two boys with severe epileptic encephalopathy dramatically reduced seizures and improved development, by selectively silencing the mutant gene while sparing the healthy copy. The 9‑year‑old needed 12 ASO doses over 24 months and could discontinue phenytoin; the 14‑year‑old received 8 doses over 16 months, with seizures dropping from about two per day to zero and notable gains in language and motor skills. This precision approach offers a middle ground between DNA editing and conventional meds and could be applicable earlier in development, though broader use and long-term effects remain to be seen.