Application of metabolomics in drug-resistant epilepsy research

Introduction: Drug resistance is a critical issue in the treatment of epileptic patients. One third of people with epilepsy are resistant to old and new antiepileptic drugs. Metabolomics could provide a tool to investigate possible markers of drug resistance in a population of epileptic subjects suggesting also a possible mechanism. Materials and methods: Blood samples were collected from 3 groups: 1) healthy patients (n=35); 2) patients “responder” (R) to the drug therapy (n=18), and 3) patients “not responder” (NR) (n=17). The samples were analysed by using a Varian UNITY INOVA 500 spectrometer. Multivariate statistical analysis was performed by using SIMCA-P+ software. The metabolites corresponding to the discriminant variables were identified and quantified by using Chenomx software. Results: A different metabolic profile was identified for the three different groups. In particular, the group of the pathological patients were characterized by an increase of acetate, acetoacetate, acetone and scyllo-inositol compared to controls group, and a decrease in lactate, glucose and citrate. The metabolic fingerprint of the class of NR was significantly different from R based on increased levels of ketone bodies. Conclusions: Metabolomics represents an important tool for biomarker discovery in drug-resistant epilepsy and for the study of the pathophysiology of this disease.