De novo mutations of the voltage-gated sodium channel gene SCN8A cause developmental and epileptic encephalopathy (DEE). Most pathogenic variants result in gain-of-function changes in activity of the sodium channel Na_v1.6, poorly controlled seizures, and significant comorbidities. In previous work, an antisense oligonucleotide (ASO) reduced Scn8a transcripts and increased lifespan after neonatal administration to a mouse model. Here, we tested long-term ASO treatment initiated after seizure onset, as required for clinical application.

中文翻译：

---

钠通道基因 Scn8a 的长期下调对 SCN8A 癫痫小鼠模型具有治疗作用

电压门控钠通道基因SCN8A的从头突变会导致发育性癫痫性脑病 (DEE)。_{大多数致病性变异会导致钠通道 Na v} 1.6活性的功能获得性变化、癫痫发作控制不佳以及严重的合并症。在之前的工作中，反义寡核苷酸 (ASO) 减少了Scn8a转录本，并在新生小鼠模型中给药后延长了寿命。在这里，我们根据临床应用的要求测试了癫痫发作后开始的长期 ASO 治疗。