Epileptogenesis, biomarkers and post-traumatic epilepsy

• Grant number: 18/24561-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2020
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luiz Eugenio Araujo de Moraes Mello
• Grantee: Luiz Eugenio Araujo de Moraes Mello
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais:( Atuais ): Beatriz de Oliveira Monteiro ; Síntia Iole Nogueira Belangero
• Pesquisadores principais:( Anteriores ): Maria da Graca Naffah Mazzacoratti
• Associated researchers: Almir Ferreira de Andrade ; Carla Baise ; Claudia da Costa Leite ; Eliana Garzon ; Maira Licia Foresti ; Manoel Jacobsen Teixeira ; Marimélia Aparecida Porcionatto ; Michele Longoni Calió ; Paulo Eduardo Luiz de Mattos ; Síntia Iole Nogueira Belangero ; Wellingson Silva Paiva
• Associated scholarship(s): 25/01988-7 - Evaluation of Biperiden Administered Post-Traumatic Brain Injury: Electroencephalographic Recording of High-Frequency Oscillations, BP.TT; 25/01841-6 - Evaluation of Biperiden Administered Post-Traumatic Brain Injury: Medication Administration, Blood Collection, and Participant Monitoring During the Intervention Phase, BP.TT; 25/02647-9 - Evaluation of biperiden administered after traumatic brain injury: electroencephalographic recording of high frequency oscillations VI, BP.TT; + associated scholarships 24/03271-0 - Evaluation of biperiden administered after traumatic brain injury: electroencephalographic recording of high frequency oscillations, BP.TT; 24/01766-1 - Evaluation of biperiden administered after traumatic brain injury: operational support activities for the project and nursing, BP.TT; 23/14992-7 - Evaluation of biperiden administered after traumatic brain injury: quality of life assessment, BP.IC; 23/11687-9 - Evaluation of biperiden administered after traumatic brain injury: comparison of clinical data with data obtained from experimental models., BP.TT; 23/04184-0 - Search for miRNAs from extracellular vesicles relevant to epileptogenesis and polygenic risk score of patients who suffered traumatic brain injury, BP.DD; 22/14055-0 - Evaluation of the prognostic potential of MicroRNAs in the development of epilepsy after traumatic brain injury, BP.PD; 22/12340-0 - Assessment of post-traumatic brain injury administered biperiden: electroencephalographic recording of high-frequency oscillations, BP.TT; 22/12399-4 - Assessment of biperiden administered after traumatic brain injury: medication administration and blood collection 2, BP.TT; 22/10520-0 - Post-traumatic Epilepsy model induced by lateral fluid percussion in non-human primates, BP.PD; 21/14564-0 - Search for miRNAs from exosomes relevant to epileptogenesis, BP.IC; 22/01718-1 - Evaluation of the effects of biperiden on convulsive behavior and microglial activation after induction of traumatic brain injury in rats, BP.IC; 20/13586-7 - Evaluation of biperiden administration in post-traumatic brain injury: post-processing of functional magnetic resonance imaging, BP.TT; 20/03377-1 - Evaluation of biperiden administered after traumatic brain injury: research management and data analysis, BP.TT; 17/05242-3 - STUDY OF THE ANTICONVULSANT EFFECT OF CANNABIDIOL AFTER TRAUMATIC BRAIN INJURY., BP.PD - associated scholarships

Abstract

Traumatic brain injury (TBI) is a public health problem, with considerable social and economic burden. TBI is one of the most important causes of secondary epilepsy. TBI leads to post-traumatic epilepsy (PTE) most likely by means of direct damage to the brain parenchyma, which in turn leads to neurodegeneration and inflammatory responses, as well as molecular, structural and electrophysiological changes (such as high frequency oscillations and cortical spreading depression). All of these changes produce anomalous circuitries that will occasionally lead to hyperexcitability. Although different classes of drugs and/or surgical procedures constitute therapeutic options for TBI damage, there is currently no treatment that prevents the development of PTE. In the course of 2 decades of experiments our group tested biperiden in order to move forward with a deeper investigation. Biperiden is an anticholinergic molecule, commonly used to treat Parkinson's disease. Biperiden was able to reduce the frequency and severity of spontaneous seizures and increase the latency for the first spontaneous seizure in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as a disease-modifying agent after TBI. In this study, we aim to investigate the safety and efficacy of biperiden in adult patients, who suffered moderate and severe TBI. Patients will be treated during the acute phase, just after trauma, as a means to avoid the epileptogenic process. Assuming we confirm our hypothesis this project will allow for: 1) characterizing a mechanism of action for treating this condition; 2) this, in turn, would open the opportunity to develop and test new molecules; 3) provide an affordable treatment option (the use of biperiden in this condition would characterize second use of a drug already available at SUS). (AU)

Scientific publications

(9)

(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)

SANABRIA, VIVIAM; ROMARIZ, SIMONE; BRAGA, MATHEUS; FORESTI, MAIRA LICIA; NAFFAH-MAZZACORATTI, MARIA DA GRACA; MELLO, LUIZ EUGENIO; LONGO, BEATRIZ M. M.. Anticholinergics: A potential option for preventing posttraumatic epilepsy. FRONTIERS IN NEUROSCIENCE, v. 16, p. 8-pg., 2023-02-24. (17/05242-3, 18/24561-5, 22/10520-0)

FORESTI, MAIRA LICIA; GARZON, ELIANA; DE MORAES, MARIANA TEICHNER; VALERIANO, RAFAEL P. S.; SANTIAGO, JOAO PAULO; DOS SANTOS, GUSTAVO MERCENAS; LONGO, NATALIA MATA; BAISE, CARLA; ANDRADE, JOAQUINA C. Q. F.; SUSEMIHL, MARIA ALICE; et al. Initial clinical evidence on biperiden as antiepileptogenic after traumatic brain injury-a randomized clinical trial. FRONTIERS IN NEUROLOGY, v. 15, p. 10-pg., 2024-08-07. (18/24561-5)

VILLENA-RUEDA, BEATRIZ ENGUIDANOS; KAJITANI, GUSTAVO SATORU; OTA, VANESSA KIYOMI; HONORATO-MAUER, JESSICA; SANTORO, MARCOS LEITE; BUGIGA, AMANDA VICTORIA GOMES; ROSA, JOICE SANTOS; ASPRINO, PAULA FONTES; MENEGHETTI, PAULA; TORRECILHAS, ANA CLAUDIA; et al. miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury. Molecular Neurobiology, v. 61, n. 11, p. 13-pg., 2024-04-26. (23/04184-0, 22/14055-0, 18/24561-5, 21/14564-0)

A.C. MOSINI; M.L. CALIÓ; M.L. FORESTI; R.P.S. VALERIANO; E. GARZON; L.E. MELLO. Modeling of post-traumatic epilepsy and experimental research aimed at its prevention. Brazilian Journal of Medical and Biological Research, v. 54, n. 2, 2020-12-18. (18/24561-5)

BENASSI, SIMONE KASTROPIL; SILVA MACEDO ALVES, JULIETA GONCALVES; GUIDORENI, CRISTIANE GORGATTI; MASSANT, CRISTINA GONCALVES; QUEIROZ, CLAUDIO M.; GARRIDO-SANABRIA, EMILIO; DE SOUZA LODUCA, RAFAEL DUARTE; SUSEMIHL, MARIA ALICE; PAIVA, WELLINGSON SILVA; DE ANDRADE, ALMIR FERREIRA; et al. Two decades of research towards a potential first anti-epileptic drug. SEIZURE-EUROPEAN JOURNAL OF EPILEPSY, v. 90, n. SI, p. 99-109, AUG 2021. (18/24561-5)

MOSINI, AMANDA C.; SANABRIA, VIVIAM; NAKAMURA, THABATTA K. E.; CALIO, MICHELE L.; POMPEU, CLARA; SILVA, CLIVANDIR S.; NICOLICHT-AMORIM, PRISCILA; NAFFAH-MAZZACORATTI, MARIA DA GRACA; PORCIONATTO, MARIMELIA A.; MELLO, LUIZ EUGENIO; et al. Posttraumatic epilepsy: Integrating clinical, inflammatory, and genetic profiles in traumatic brain injury patients. Epilepsy Research, v. 205, p. 8-pg., 2024-07-17. (22/10520-0, 18/24561-5)

SANABRIA, VIVIAM; ROMARIZ, SIMONE A. A.; BRAGA, MATHEUS; PIRES, JAIME MOREIRA; NAFFAH-MAZZACORATTI, MARIA DA GRACA; MELLO, LUIZ EUGENIO; LONGO, BEATRIZ M.; FORESTI, MAIRA LICIA. What we have learned from non-human primates as animal models of epilepsy. Epilepsy & Behavior, v. 154, p. 10-pg., 2024-03-21. (18/24561-5, 17/05242-3, 22/00249-8)

FORESTI, MAIRA LICIA; GARZON, ELIANA; GOMES PINHEIRO, CARLA CRISTINA; PACHECO, RAFAEL LEITE; RIERA, RACHEL; MELLO, LUIZ EUGENIO. Biperiden for prevention of post-traumatic epilepsy: A protocol of a double-blinded placebo-controlled randomized clinical trial (BIPERIDEN trial). PLoS One, v. 17, n. 9, p. 11-pg., 2022-09-09. (18/24561-5)

MOSINI, A. C.; MAZZONETTO, P. C.; CALIO, M. L.; POMPEU, C.; MASSINHANI, F. H.; NAKAMURA, T. K. E.; PIRES, J. M.; SILVA, C. S.; PORCIONATTO, M. A.; MELLO, L. E.. Temporal pattern of Fos and Jun families expression after mitogenic stimulation with FGF-2 in rat neural stem cells and fibroblasts. Brazilian Journal of Medical and Biological Research, v. 56, p. 8-pg., 2023-01-01. (18/24561-5)