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Detection of methylated circulating DNA as a non-invasive biomarker for the identification of patients with mesial temporal lobe epilepsy and ischemic stroke

Grant number: 17/26167-0
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2019
Effective date (End): March 21, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Iscia Teresinha Lopes Cendes
Grantee:Danielle do Carmo Ferreira Bruno
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID
Associated scholarship(s):20/16213-7 - Multiomics analysis of the regulome and transcriptome at the single-cell resolution in mesial temporal lobe epilepsy with hippocampal sclerosis, BE.EP.PD


Currently, the diagnosis of patients with stroke and epilepsy is still a great challenge, since it is based on subjective clinical signs and symptoms. Therefore, the identification of biomarkers for the diagnosis and for the establishment of prognosis becomes essential. Methylated cell free circulating DNAs (cfDNAs) have recently emerged as candidates for biomarkers, since they can be easily analyzed and quantified noninvasively. In addition, disease-specific DNA methylation patterns may undergo changes in response to treatment, increasing the possibility that biomarkers based on DNA methylation are used for monitoring treatment efficacy. In this context, the main objective of this project is to investigate whether differentially methylated cfDNA can be used to aid in the diagnosis, in the establishment of prognosis and in the prediction of treatment response in epilepsy and stroke. We will study 100 patients with epilepsy, 100 with stroke, and 100 control subjects. All patients included in the study are prospectively followed at the UNICAMP university hospital according to a detailed research protocol that includes extensive clinical and neuroimaging evaluation. All phenotypic information is included in a database built especially for the research projects. Determination of overall methylation pattern of cfDNA will be performed by whole genome sequencing of bisulphite-treated plasma free DNA. Subsequently, patients will be sub-divided into groups according to response to treatment and prognosis. If necessary, additional patients may be included in confirmatory studies, since our biobank has currently samples of more than 700 patients with epilepsy and 300 patients with stroke. Studies on epilepsy and stroke are the main focus of the BRAINN group. In addition, the comparison of the methylation pattern of cfDNA between these two neurological conditions is of interest in the study of the mechanisms of brain damage and plasticity.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
D.C.F. BRUNO; A. DONATTI; M. MARTIN; V.S. ALMEIDA; J.C. GERALDIS; F.S. OLIVEIRA; D.B. DOGINI; I. LOPES-CENDES. Circulating nucleic acids in the plasma and serum as potential biomarkers in neurological disorders. Brazilian Journal of Medical and Biological Research, v. 53, n. 10, . (15/19768-1, 17/26167-0, 13/07559-3, 17/23954-0, 15/25607-0, 16/26172-0)
BRUXEL, ESTELA M.; DO CANTO, AMANDA M.; BRUNO, DANIELLE C. F.; GERALDIS, JAQUELINE C.; LOPES-CENDES, ISCIA. Multi-omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy. EPILEPSIA OPEN, . (19/25948-3, 20/06168-4, 13/07559-3, 18/03254-7, 17/26167-0)
BRUXEL, ESTELA M.; BRUNO, DANIELLE C. F.; DO CANTO, AMANDA M.; GERALDIS, JAQUELINE C.; GODOI, ALEXANDRE B.; MARTIN, MARIANA; LOPES-CENDES, ISCIA. Multi-omics in mesial temporal lobe epilepsy with hippocampal sclerosis: Clues into the underlying mechanisms leading to disease. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, v. 90, n. SI, p. 34-50, . (20/06168-4, 19/25948-3, 18/03254-7, 19/20953-9, 19/00213-0, 17/26167-0)

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