Fig. 1.

Aquarium-to-bedside drug development for epilepsy. Genes associated with rare genetic epilepsies, such as Dravet syndrome (DS), have been identified in patients. Genetically modified zebrafish models generated using ENU-mutagenesis or CRISPR-Cas9 technology can recapitulate these rare genetic epilepsies. Locomotion-based and local field potential (LFP) recording techniques adapted to larval zebrafish can then be used to study these rare genetic epilepsy models. Sensitive phenotype-based screening of hundreds to thousands of drugs can be achieved using a combination of these behavioral and electrophysiological assays in genetically modified zebrafish models, and use of a DS zebrafish model identified several drugs that progressed directly into clinical or compassionate-use trials.