**6. Antiepileptic therapy and beyond**

At present, the treatment of epilepsy is still dominated by drugs. More than 35% of marketed antiepileptic drugs target VGICs, such as phenytoin, carbamazepine, oxcarbazepine, and ethosuximide. Phenytoin and carbamazepine are broad-spectrum antiepileptic drugs blocking VGSCs as their primary mechanism of action. For example, phenytoin is a more effective inhibitor of SCN8A-I1327V than other drugs [112], which could be used in treating patients with gain-of-function mutations of SCN8A. Different types of VGCCs play different roles in the pathological process of epilepsy. Decreased expression of P/Q type could induce epilepsy, whereas increased expression of N-type and T-type calcium channels could lead to epilepsy. Calcium blockers including ethosuximide have been widely accepted for the treatment of absence epilepsy [71]. Gain-of-function BK channels contribute to epileptogenesis and seizure generation. BK-blocking agents, like paxilline [49], might be used as potential therapeutic drugs.

In the future, novel techniques might contribute to develop reasonable therapies for treating inherited or acquired epileptic syndromes. For instance, induced pluripotent stem cells (IPS) and genetically engineering animal models could be used for accurate treatments of epilepsy. Single-nucleotide polymorphisms (SNPs) of VGIC genes from hereditary epilepsy patients could be detected by *de novo* genomic sequencing. VGICs of IPS cells could be mutated by CRISPR-Cas9 according to the information of these SNPs [113]. Through inducing IPS cells differentiated into neurons, phenotype of VGIC gene SNPs could be well investigated. It is also a well-detection platform for selecting antiepileptic drugs that would be sensitive to mutated VGICs *in vitro* [112]. For *in vivo*

tests, besides transgenic mice, construction of nematode or zebrafish epileptic models may be creating a shortcut for choosing suitable and personalized antiepileptic drugs [114, 115]. In addition to drug control, optogenetics and ultrasonic control are hopeful to suppress the epileptic seizures induced by VGIC dysfunction [116, 117].
