Voltage-Gated Sodium Channels as Drug Targets in Epilepsy-Related Sodium Channelopathies

Voltage-gated sodium channels (VGSCs) drive cellular excitability in various cells including the neurons of the central nervous system. Genetic variants in the genes encoding the brain-expressed VGSCs have been identified in patients with severe epilepsy syndromes making clear that proper VGSC activity is required for normal neurological development and function. Given this central role in determining neuronal physiology, VGSCs are one of the most common molecular targets for currently available antiseizure medications. Yet the significant limitations of existing medications indicate a need for novel therapeutic strategies, including more precise modulation of VGSC function. In this chapter, we discuss ongoing precision medicine approaches targeting VGSCs in the treatment of epilepsy-related sodium (Na) channelopathies. Notwithstanding significant technical hurdles, modulators of VGSCs are likely to remain a mainstay in the treatment of epilepsy-related channelopathies and epilepsy more generally.