Protective effect of the ketogenic diet in Scn1a mutant mice

Dutton, Stacey B. B., Sawyer, Nikki T., Kalume, Franck, Jumbo-Lucioni, Patricia, Borges, Karin, Catterall, William A. and Escayg, Andrew (2011) Protective effect of the ketogenic diet in Scn1a mutant mice. Epilepsia, 52 11: 2050-2056. doi:10.1111/j.1528-1167.2011.03211.x

Author Dutton, Stacey B. B.
Sawyer, Nikki T.
Kalume, Franck
Jumbo-Lucioni, Patricia
Borges, Karin
Catterall, William A.
Escayg, Andrew
Title Protective effect of the ketogenic diet in Scn1a mutant mice
Formatted title
Protective effect of the ketogenic diet in Scn1a mutant mice
Journal name Epilepsia   Check publisher's open access policy
ISSN 0013-9580
Publication date 2011-07-29
Sub-type Article (original research)
DOI 10.1111/j.1528-1167.2011.03211.x
Volume 52
Issue 11
Start page 2050
End page 2056
Total pages 7
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2012
Language eng
Formatted abstract
Purpose:  We evaluated the ability of the ketogenic diet (KD) to improve thresholds to flurothyl-induced seizures in two mouse lines with Scn1a mutations: one that models Dravet syndrome (DS) and another that models genetic (generalized) epilepsy with febrile seizures plus (GEFS+).
Methods:  At postnatal day 21, mouse models of DS and GEFS+ were fasted for 12–14 h and then placed on either a 6:1 (fats to proteins and carbohydrates) KD or a standard diet (SD) for 2 weeks. At the end of the 2-week period, we measured thresholds to seizures induced by the chemiconvulsant flurothyl. Body weight, β-hydroxybutyrate (BHB) levels, and glucose levels were also recorded every 2 days over a 2-week period in separate cohorts of mutant and wild-type mice that were either on the KD or the SD.
Key Findings:  Mice on the KD gained less weight and exhibited significantly higher BHB levels compared to mice on the SD. It is notable that thresholds to flurothyl-induced seizures were restored to more normal levels in both mouse lines after 2 weeks on the KD.
Significance:  These results indicate that the KD may be an effective treatment for refractory patients with SCN1A mutations. The availability of mouse models of DS and GEFS+ also provides an opportunity to better understand the mechanism of action of the KD, which may facilitate the development of improved treatments.
Keyword Dravet syndrome
Genetic epilepsy with febrile seizures plus
Mouse models
Ketogenic diet
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Early View. Online 29 JUL 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 26 Sep 2011, 11:00:44 EST by Dr Karin Borges on behalf of School of Biomedical Sciences