A UC San Diego-led team reported in Nature Medicine that personalized antisense oligonucleotides (ASOs) reduced seizure frequency in boys with rare SCN2A-related developmental and epileptic encephalopathies. The approach uses individualized ASO designs based on the specific inherited variant, including gain-of-function and mixed loss-/gain-of-function configurations. The study describes two boys who had seizures refractory to more than 10 antiseizure medications. Researchers said ASO treatment decreased seizure burden and enabled one patient to walk independently, while also positioning the strategy as disease-root targeting for single-variant disorders. Ionis Pharmaceuticals supported the development and testing of the ASOs used in the work. Researchers framed the technique as especially suited to rare and ultra-rare neurological diseases where variant-specific biology is actionable.