Abstract
Background: Ketogenic dietary therapies (KDT) are used as a treatment in childhood epilepsy. However, their mechanism has not yet been established. The main objective of this study was to determine the changes in the transcriptomic profile induced by KDT in children with epilepsy in order to shed light on its possible mechanisms. Methods: Eight children with refractory epilepsy were enrolled in the study. Peripheral blood mononuclear cells were obtained before and after the children were treated with KDT for a minimum of 6 months. RNA was extracted and mRNA and miRNA profiling were performed and analyzed. Results: Our intervention with KDT significantly reduced the seizure number in seven of the eight paediatric patients treated and caused important changes in their gene expression profile. Our study reveals modifications in the transcription of 4630 genes and 230 miRNAs. We found that the genes involved in the protection against epileptic crises were among those mainly changed. These genes collectively encode for ion channels, neurotransmitter receptors, and synapse structural proteins. Conclusions: Together our results explain the possible mechanisms of KDT and reinforce its clinical importance in the treatment of epilepsy.
Highlights
The global incidence of epilepsy is about 60 per 100,000 inhabitants per year, and up to a third of patients may suffer from refractory epilepsy [1, 2]
Eight children with refractory epilepsy were treated with a Ketogenic dietary therapies (KDT) (Table 1 and Supplementary Table 1)
The median number of antiseizure medications (ASM) used before the onset of KDT was 4 and no patient was treated with epilepsy surgery prior to KDT
Summary
The global incidence of epilepsy is about 60 per 100,000 inhabitants per year, and up to a third of patients may suffer from refractory epilepsy [1, 2]. An alternative treatment to antiseizure medications (ASM) are the ketogenic dietary therapies (KDT), which have been used as a treatment for refractory epilepsy in children since the 1920s [3]. Ketogenic dietary therapies (KDT) are used as a treatment in childhood epilepsy. Their mechanism has not yet been established. The main objective of this study was to determine the changes in the transcriptomic profile induced by KDT in children with epilepsy in order to shed light on its possible mechanisms. Our study reveals modifications in the transcription of 4630 genes and 230 miRNAs. We found that the genes involved in the protection against epileptic crises were among those mainly changed. Conclusions: Together our results explain the possible mechanisms of KDT and reinforce its clinical importance in the treatment of epilepsy
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