Drug repurposing for Dravet syndrome in scn1Lab −/− mutant zebrafish

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Behavioral Comorbidities and Drug Treatments in a Zebrafish scn1lab Model of Dravet Syndrome

Loss-of-function mutations in SCN1A cause Dravet syndrome (DS), a catastrophic childhood epilepsy in which patients experience comorbid behavioral conditions, including movement disorders, sleep abnormalities, anxiety, and intellectual disability. To study the functional consequences of voltage-gated sodium channel mutations, we use zebrafish with a loss-of-function mutation in scn1lab, a zebra...

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Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment.

Dravet syndrome is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterize zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneou...

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Altered Glycolysis and Mitochondrial Respiration in a Zebrafish Model of Dravet Syndrome.

Altered metabolism is an important feature of many epileptic syndromes but has not been reported in Dravet syndrome (DS), a catastrophic childhood epilepsy associated with mutations in a voltage-activated sodium channel, Nav1.1 (SCN1A). To address this, we developed novel methodology to assess real-time changes in bioenergetics in zebrafish larvae between 4 and 6 d postfertilization (dpf). Base...

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A Novel Long-term, Multi-Channel and Non-invasive Electrophysiology Platform for Zebrafish

Zebrafish are a popular vertebrate model for human neurological disorders and drug discovery. Although fecundity, breeding convenience, genetic homology and optical transparency have been key advantages, laborious and invasive procedures are required for electrophysiological studies. Using an electrode-integrated microfluidic system, here we demonstrate a novel multichannel electrophysiology un...

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Dravet syndrome

"Dravet syndrome" (DS) previously named severe myoclonic epilepsy of infancy (SMEI), or epilepsy with polymorphic seizures, is a rare disorder characterized by an early, severe, generalized, epileptic encephalopathy.DS is characterized by febrile and afebrile seizures beginning in the 1st year of life followed by different types of seizures (either focal or generalized), which are typically res...

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ژورنال

عنوان ژورنال: Epilepsia

سال: 2019

ISSN: 0013-9580,1528-1167

DOI: 10.1111/epi.14647