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| 2019/03/16 |
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in vivo Phenomic Screening System for Antiepileptic Drugs using Dravet Syndrome Zebrafish Model
in vivo Phenomic Screening System for Antiepileptic Drugs
using Dravet Syndrome Zebrafish Model
Mina Okamura1,2, Ikuko Mikami1,2, Junko Koiwa1,2, Yuka Takahashi1,2
,Erina Kitahara1,2, Mayuko Okuno1,2, Shota Sasagawa1,2, Yuhei Nishimura3 ,Toshio Tanaka1,2
1Dept. Systems Pharmacology, Grad. Sch. Med., Mie University, 2Medical Zebrafish Research
Center, Mie Univ., 3Dept. Integrative Pharamacology, Grad. Sch. Med., Mie Univ.
in vivo Phenomic Screening System for Antiepileptic Drugs using Dravet Syndrome Zebrafish Model
Epilepsy is a common chronic neurological disease affecting almost 1 million people in Japan and 50million people worldwide. Despite availability of more than two dozen FDA-approved antiepileptic
drugs, one-third of patients fail to receive adequate seizure control. Specifically, pediatric genetic epilepsies are often the most severe, debilitating and pharmaco-resistant forms of epilepsy.
The discovery of epilepsy associated genes suggests varied underlying pathologies and opens the door for development of precision medicine for each genetic epilepsy. Over 80% of patients diagnosed with Dravet syndrome carry a de novo mutation within the voltage-gated sodium channel gene SCN1A and these patients suffer with drug resistant and life-threatening seizures. Here we have developed zebrafish models for Dravet syndrome featuring inactivation of SCN1A with an emphasis
on phenomics. we will also report recent drug screening efforts using our models with a focus on assay protocols and predictive pharmacological profiles. As the discovery and development phase
rapidly moves from the lab-to-the-clinic for Dravet syndrome, it is hoped that this zebrafish-based drug discovery strategy offers a platform for how to approach any genetic epilepsy.
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