Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy

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Godoi, Alexandre B. ; do Canto, Amanda M. ; Donatti, Amanda ; Rosa, Douglas C. ; Bruno, Danielle C. F. ; Alvim, Marina K. ; Yasuda, Clarissa L. ; Martins, Lucas G. ; Quintero, Melissa ; Tasic, Ljubica ; Cendes, Fernando ; Lopes-Cendes, Iscia

• Tipo de documento: Artigo Científico
• Fonte: METABOLITES; v. 12, n. 5, p. 16-pg., 2022-05-01.

Resumo

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of disease in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi-and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), beta-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores > 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE. (AU)

• Processo FAPESP: 21/04451-3 - Treinamento técnico em análise metabolômica na busca por biomarcadores em doenças neurológicas
• Beneficiário: Melissa Quintero Escobar
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
• Beneficiário: Fernando Cendes
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/00213-0 - Análise metabolômica do plasma de pacientes com epilepsia do lobo temporal mesial: busca por biomarcadores de refratariedade medicamentosa
• Beneficiário: Alexandre Barcia de Godoi
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/24069-3 - Do biomonitoramento ao reconhecimento de assinaturas do exposoma humano visando antecipar riscos para uma saúde contínua
• Beneficiário: Fernando Barbosa Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/04441-8 - Análise de biomarcadores moleculares em pacientes com acidente vascular cerebral
• Beneficiário: Amanda Donatti
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 19/00048-0 - Perfil metabólico de pacientes com acidente vascular cerebral isquêmico: busca por biomarcadores
• Beneficiário: Douglas Cescon da Rosa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 19/25948-3 - Análise de sinaptossomos isolados do hipocampo de pacientes com Epilepsia Do Lobo Temporal Mesial utilizando ferramentas de proteômica e metabolômica
• Beneficiário: Amanda Morato Do Canto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/26167-0 - Detecção de DNA circulante metilado como biomarcador não invasivo para identificação de pacientes com epilepsia do lobo temporal mesial e acidente vascular cerebral isquêmico
• Beneficiário: Danielle do Carmo Ferreira Bruno
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado