Multi-omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy

Author(s)

Bruxel, Estela M. ^{[1, 2]} ; do Canto, Amanda M. ^{[1, 2]} ; Bruno, Danielle C. F. ^{[1, 2]} ; Geraldis, Jaqueline C. ^{[1, 2]} ; Lopes-Cendes, Iscia ^{[1, 2]}

Affiliation

^[1] Brazilian Inst Neurosci & Neurotechnol BRAINN, Campinas - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Dept Translat Med, Sch Med Sci, Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

• Document type: Review article
• Source: EPILEPSIA OPEN; OCT 2021.
• Web of Science Citations: 0

Abstract

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults, and hippocampal sclerosis (HS) is a frequent histopathological feature in patients with MTLE. Pharmacoresistance is present in at least one-third of patients with MTLE with HS (MTLE+HS). Several hypotheses have been proposed to explain the mechanisms of pharmacoresistance in epilepsy, including the effect of genetic and molecular factors. In recent years, the increased knowledge generated by high-throughput omic technologies has significantly improved the power of molecular genetic studies to discover new mechanisms leading to disease and response to treatment. In this review, we present and discuss the contribution of different omic modalities to understand the basic mechanisms determining pharmacoresistance in patients with MTLE+HS. We provide an overview and a critical discussion of the findings, limitations, new approaches, and future directions of these studies to improve the understanding of pharmacoresistance in MTLE+HS. However, it is important to point out that, as with other complex traits, pharmacoresistance to anti-seizure medications is likely a multifactorial condition in which gene-gene and gene-environment interactions play an important role. Thus, studies using multidimensional approaches are more likely to unravel these intricate biological processes. (AU)

• FAPESP's process: 19/25948-3 - Analysis of synaptosomes isolated from hippocampus tissue of patients with Mesial Temporal Lobe Epilepsy using proteomics and metabolomics
• Grantee: Amanda Morato Do Canto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/06168-4 - Studying the role of genomic cis-regulatory elements in the mechanisms underlying Mesial Temporal Lobe Epilepsy
• Grantee: Jaqueline Cruz Geraldis
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/03254-7 - Using expression quantitative-trait association studies (eGWAS) to identify loci for mesial temporal lobe epilepsy
• Grantee: Estela Maria Bruxel
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/26167-0 - Detection of methylated circulating DNA as a non-invasive biomarker for the identification of patients with mesial temporal lobe epilepsy and ischemic stroke
• Grantee: Danielle do Carmo Ferreira Bruno
• Support Opportunities: Scholarships in Brazil - Post-Doctoral