A UC San Diego-led team reported personalized antisense oligonucleotide (ASO) approaches for two boys with rare SCN2A-related developmental and epileptic encephalopathies, with results published in Nature Medicine. Researchers designed individualized ASOs based on inherited pathogenic SCN2A variants and reported seizure reductions and functional gains. The study included a nine-year-old with a heterozygous SCN2A gain-of-function variant and a 14-year-old with a mixed loss- and gain-of-function variant. Both children had nonverbal status and seizures that failed to respond to more than 10 antiseizure medications. Ionis Pharmaceuticals supported aspects of ASO design and testing, according to communications tied to the research. The team described reductions in seizure frequency and reported one patient was able to walk independently, aligning with the intended disease-modifying mechanism of targeting disease-driving gene expression. The work underscores how variant-specific ASO design can be leveraged for ultra-rare neurological conditions where multiple pathogenic variants can produce distinct clinical phenotypes.