Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment.
Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment.
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DOI：
10.1038/ncomms3410
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发表时间：
2013
影响因子：
16.6
通讯作者：
Hortopan, Gabriela A.
中科院分区：
文献类型：
--
作者：
Baraban, Scott C.;Dinday, Matthew T.;Hortopan, Gabriela A.
Dravet syndrome (DS) 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 characterise zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviors. Although scn1Lab expression is reduced, microarray analysis is remarkable for the small fraction of differentially expressed genes (~3%) and lack of compensatory expression changes in other scn subunits. Ketogenic diet, diazepam, valproate, potassium bromide and stiripentol attenuate mutant seizure activity; seven other antiepileptic drugs have no effect. A phenotype-based screen of 320 compounds identifies a US Food and Drug Administration-approved compound (clemizole) that inhibits convulsive behaviors and electrographic seizures. This approach represents a new direction in modeling pediatric epilepsy and could be used to identify novel therapeutics for any monogenic epilepsy disorder.
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影响因子：
46.9
作者：
Einav, Shirit;Gerber, Doron;Bryson, Paul D.;Sklan, Ella H.;Elazar, Menashe;Maerkl, Sebastian J.;Glenn, Jeffrey S.;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
3.8
作者：
Ceulemans, BPGM;Claes, LRF;Lagae, LG
通讯作者：
Lagae, LG
DOI：
10.1002/jps.3030490107
发表时间：
1960-01-01
期刊：
JOURNAL OF THE AMERICAN PHARMACEUTICAL ASSOCIATION
影响因子：
--
作者：
FINKELSTEIN, M;KROMER, CM;DELAHUNT, CS
通讯作者：
DELAHUNT, CS
影响因子：
5.3
作者：
Hunt RF;Hortopan GA;Gillespie A;Baraban SC
通讯作者：
Baraban SC
影响因子：
--
作者：
Jordan, ChaRandle;Li, Hong Hua;Francke, Uta
通讯作者：
Francke, Uta