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- Frontiers in Systems Pharmacogy
| 2018/11/07 |
|
phenomic screening by Dravet syndrome zebrafish model
Epilepsy is a common chronic neurological disease affecting almost 1 million people in Japan and 50 million 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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