Translational Platform for Epilepsy Therapy and Biomarker Discovery

癫痫治疗和生物标志物发现的转化平台

• 批准号: 10605283
• 负责人: Denes V. Agoston
• 金额: $ 212.24万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605283
• 关键词: Acceleration; Acute; Advisory Committees; Advocate; Anatomy; Animal Model; Anticonvulsants; Antiepileptogenic; Autophagocytosis; Axon; Bioinformatics; Biological Markers; Blood; Blood Vessels; Brain; Brain Pathology; Calcium-Binding Proteins; California; Caring; Cell Death; Cessation of life; Classification; Clinical; Collaborations; Corpus Callosum; Data; Deposition; Development; Discriminant Analysis; Disease; Double-Blind Method; Early Post-Traumatic Seizures; Early treatment; Electroencephalography; Epilepsy; Epileptogenesis; External Capsule; Free Radicals; Funding; Future; Glial Fibrillary Acidic Protein; Guidelines; HMGB1 gene; Health Services; Hemorrhage; High Frequency Oscillation; Image; Inflammatory; Injury; Interferon Type II; Interleukin-1 beta; International; Intervention; Investigation; Iron; Iron Chelation; Isoenzymes; Laboratories; Lateral; Learning; Levetiracetam; Link; Machine Learning; Magnetic Resonance Imaging; Medicine; Memory; Metabolic; Minnesota; Modeling; Modification; Molecular; Monitor; Motor; National Institute of Neurological Disorders and Stroke; Neuroglia; Neurons; Oxidative Stress; Pathologic; Pathology; Patients; Peripheral; Persons; Physiological; Plasma; Populations at Risk; Post-Traumatic Epilepsy; Pre-Clinical Model; Preclinical Testing; Predictive Value; Process; Randomized; Rattus; Recovery of Function; Research; Risk; Risk Factors; Seizures; Site; Testing; Therapeutic; Time; Tissues; Translational Research; Traumatic Brain Injury; Universities; University Health Services; Visuospatial; acquired epilepsy; biomarker discovery; biomarker identification; biomarker panel; biomarker selection; brain magnetic resonance imaging; candidate marker; clinical practice; college; design; early detection biomarkers; efficacy testing; experience; fluid percussion injury; functional outcomes; high standard; histological stains; improved; in vivo; multimodality; neuroimaging; novel; novel marker; pharmacokinetic model; pre-clinical; predictive marker; prevent; primary endpoint; prophylactic; protein biomarkers; standard of care; synergism; tau Proteins; tau-1; treatment response; ubiquitin C-terminal hydrolase

PROJECT SUMMARY There is currently no validated treatment to prevent the development of acquired epilepsies, such as post- traumatic epilepsy. The availability of biomarker that predicts, at an early stage, people at risk to develop epilepsy and benefit from treatment interventions would significantly accelerate and de-risk the process of identifying an antiepileptogenic therapy. In this study, that is based on collaborations and preliminary data derived from EpiBioS4Rx, an NINDS funded Center without Walls, we aim to create a rigorous and effective preclinical model to screen a new candidate treatment to prevent posttraumatic epilepsy in the lateral fluid percussion injury model as well as identify biomarkers to guide treatment implementation. We will follow a multicenter, double-blinded, vehicle-controlled, randomized preclinical antiepileptogenesis study following the high standards of rigor advocated by NINDS, the AES/ILAE Translational Research Task Force and the ARRIVE guidelines. We have formed a collaborative group of four international preclinical testing centers (Albert Einstein College of Medicine, University of Melbourne, two UCLA sites), supported by experts in pharmacokinetic modeling (University of Minnesota), protein biomarker research (Uniformed Services University of the Health Services) and bioinformatics (University of Southern California). We plan to test a compound that removes pathological iron stores from the brain and test whether it can modify early biomarkers of epileptogenesis and injury. We aim to identify (a) at least one panel of multimodal biomarkers that can predict early on treatment response to the iron chelator, including the development of post-traumatic epileptogenesis, (b) at least one biomarker of epileptogenesis, (c) and determine whether iron chelator treatment can prevent post-traumatic epilepsy development.

项目总结