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Published on: July 12, 2021
Protective effect of the ketogenic diet in Scn1a mutant mice
Stacey B B Dutton1, Nikki T Sawyer, Franck Kalume
1Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA.
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.
