title: Protective effect of the ketogenic diet in Scn1a mutant mice.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Stacey B B
authors.initials: SB
authors.lastname: Dutton
authors.forename: Nikki T
authors.initials: NT
authors.lastname: Sawyer
authors.forename: Franck
authors.initials: F
authors.lastname: Kalume
authors.forename: Patricia
authors.initials: P
authors.lastname: Jumbo-Lucioni
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
authors.forename: Andrew
authors.initials: A
authors.lastname: Escayg
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D003292:Convulsants / Q000494:pharmacology; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004829:Epilepsy, Generalized / Q000178:diet therapy* / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000235:genetics; D005481:Flurothyl / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D015430:Weight Gain
chemical_list: D003292:Convulsants; D053503:Epithelial Sodium Channels; C507047:Scnn1a protein, mouse; D005481:Flurothyl; D020155:3-Hydroxybutyric Acid