Advancing epilepsy treatment through personalized genetic zebrafish models.
With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts.
Epilepsy Research Laboratory, University of California, San Francisco, CA, United States.
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Griffin
Epilepsy Research Laboratory, University of California, San Francisco, CA, United States.
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Krasniak
Epilepsy Research Laboratory, University of California, San Francisco, CA, United States. Electronic address: scott.baraban@ucsf.edu.
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Baraban
D000818:Animals; D030801:Animals, Genetically Modified; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D000927:Anticonvulsants; D029961:Zebrafish Proteins
Antiepileptic; Drug discovery; Epilepsy; High throughput; Pharmacology; Zebrafish