Dados do Trabalho

Título

Using ¹H-NMR-based metabolomics to identity candidate biomarkers of drug resistance in patients with mesial temporal lobe epilepsy

Introdução

The most prevalent type of epilepsy in adults is mesial temporal lobe epilepsy (MTLE), which stands out due to the high frequency of patients with refractory seizures. Because of the challenge of predicting which patients will respond to treatment with antiseizure medication (ASM), alternative therapies such as epilepsy surgery may take many years to be indicated.

Objetivo

Using metabolomics, we aim to identify biomarkers of drug-resistant epilepsy among patients with MTLE.

Método

We studied patients with MTLE, divided into two groups according to their response to pharmacological treatment: responsive and resistant to ASMs. We also included samples from controls. All patients in this study were using the same ASDs, clobazam combined with carbamazepine. The plasmatic metabolic profile of these groups was determined by liquid-state NMR data acquisition combined with chemometric analysis. The obtained spectra were processed using MestreNova and Matlab software and then analyzed using Metaboanalyst and the HMDB database. The discriminant metabolites were determined based on the VIP score's highest values from the PLS-DA model.

Resultados

We analyzed 56 samples, 18 patients resistant to ASM, ten responsive, and 28 controls. Overall, we identified 27 known metabolites belonging to several classes of biomolecules, such as amino acids, lipids, carbohydrates, and others. However, only a few metabolites could discriminate patients from controls, glucose (p=0.01), saturated lipids (p=0.0002), isoleucine (p=0.0001) and beta-hydroxybutyrate (p=0.0003) and proline (p=0.02). Most importantly, when comparing the two groups of patients, we found suggestive discrimination power for lactate, glucose, lipoproteins, unsaturated lipids, isoleucine, and proline.

Conclusão

Albeit none of the metabolites identified in our study could conclusively identify patients with resistant MTLE, we found several metabolic biomarkers which can be further explored in a larger group of patients with MTLE.

Palavras-chave

Mesial Temporal Lobe Epilepsy; Metabolomics; Drug resistance; ¹H-NMR Spectroscopy