SCN8A-ABE

SCN8A-ABE is an experimental gene therapy designed to treat SCN8A developmental and epileptic encephalopathy (DEE) by utilizing adenine base editing technology. The therapy consists of an adenine base editor and a guide RNA packaged within an adeno-associated virus (AAV) vector, specifically the PhP.eB variant for efficient CNS delivery. It targets the R1872W gain-of-function mutation in the SCN8A gene, which encodes the Nav1.6 sodium channel. By converting the pathogenic adenine to guanine, SCN8A-ABE restores the wild-type sequence, thereby normalizing the pathological persistent sodium current (INaP) and reducing neuronal hyperexcitability. Preclinical studies in mouse models have demonstrated that this approach can significantly reduce seizure frequency, prevent sudden unexpected death in epilepsy (SUDEP), and improve behavioral comorbidities.