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Author Notes:

Corresponding Author: Andrew Escayg, Ph.D., Emory University School of Medicine, Department of Human Genetics, 615 Michael Street, Whitehead Building, Suite 301, Atlanta, Georgia 30322, Telephone number: (404) 712-8328, Fax number: (404) 727-3949, aescayg@emory.edu

Subject:

Research Funding:

This study was supported by grants from the NIH (R21 NS06615 to AE, R01 NS25704 to WAC, 1F31 NS065694 to SBBD, and K01 NS062862 to FK) and by a predoctoral fellowship from the Epilepsy Foundation (SBBD).

Keywords:

  • Dravet syndrome
  • genetic epilepsy with febrile seizures plus
  • mouse models
  • ketogenic diet
  • SCN1A

Protective effect of the ketogenic diet in Scn1a mutant mice

Tools:

Journal Title:

Epilepsia

Volume:

Volume 52, Number 11

Publisher:

, Pages 2050-2056

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Summary 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 hours and then placed on either a 6:1 KD or a standard diet (SD) for two weeks. At the end of the two-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 two days over a two-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. Importantly, thresholds to flurothyl-induced seizures were restored to more normal levels in both mouse lines after two 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.

Copyright information:

© 2011 International League Against Epilepsy

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