Journal article
Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death
Proceedings of the National Academy of Sciences of the United States of America, Vol.115(34), pp.E8077-E8085
2018
Abstract
Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel NaV1.1. Brain NaV1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of NaV1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet syndrome mice without affecting the firing of excitatory neurons. Intracerebroventricular infusion of Hm1a rescues Dravet syndrome mice from seizures and premature death. This precision medicine approach, which specifically targets the molecular deficit in Dravet syndrome, presents an opportunity for treatment of this intractable epilepsy.
Details
- Title
- Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death
- Authors
- K L Richards (Author)C J Milligan (Author)R J Richardson (Author)N Jancovski (Author)M Grunnet (Author)L H Jacobson (Author)E A B Undheim (Author)M Mobli (Author)C Y Chow (Author)Volker Herzig (Author) - University of QueenslandA Csoti (Author)G Panyi (Author)C A Reid (Author)G F King (Author)S Petrou (Author)
- Publication details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.115(34), pp.E8077-E8085
- Publisher
- National Academy of Sciences
- Date published
- 2018
- DOI
- 10.1073/pnas.1804764115
- ISSN
- 0027-8424
- Copyright note
- Copyright © 2018. This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450960502621
- Output Type
- Journal article
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