Individualized Antisense Oligonucleotides for SCN2A Related Developmental Epileptic Encephalopathy

The research operates within the established paradigm of precision medicine, specifically using antisense oligonucleotide (ASO) technology to treat monogenic neurological disorders. It further relies on the paradigm of using whole-genome sequencing to identify patient-specific genetic variants that enable highly targeted therapeutic design. The study aims to solve the puzzle of treating SCN2A gain-of-function variants, where non-selective gene suppression is undesirable.

This paper is classified as Normal Science because it does not challenge the fundamental principles of ASO therapy but rather articulates and extends them. The researchers apply existing concepts to a new, highly specific problem by designing individualized, allele-selective ASOs for two patients. This "n-of-1" approach is a sophisticated form of puzzle-solving within the current precision medicine paradigm. The successful clinical outcomes reinforce the paradigm's efficacy and demonstrate its potential for extreme personalization, expanding its scope without introducing revolutionary concepts or revealing critical anomalies in the existing framework.