Personalized translational epilepsy research — Novel approaches and future perspectives

• Published in: Epilepsy & behavior Vol. 76; pp. 7 - 12
• Main Authors: Bauer, Sebastian, van Alphen, Natascha, Becker, Albert, Chiocchetti, Andreas, Deichmann, Ralf, Deller, Thomas, Freiman, Thomas, Freitag, Christine M., Gehrig, Johannes, Hermsen, Anke M., Jedlicka, Peter, Kell, Christian, Klein, Karl Martin, Knake, Susanne, Kullmann, Dimitri M., Liebner, Stefan, Norwood, Braxton A., Omigie, Diana, Plate, Karlheinz, Reif, Andreas, Reif, Philipp S., Reiss, Yvonne, Roeper, Jochen, Ronellenfitsch, Michael W., Schorge, Stephanie, Schratt, Gerhard, Schwarzacher, Stephan W., Steinbach, Joachim P., Strzelczyk, Adam, Triesch, Jochen, Wagner, Marlies, Walker, Matthew C., von Wegner, Frederic, Rosenow, Felix
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2017
• Subjects: Biomarkers; New treatment targets; Personalized medicine; Precision medicine; Treatment targets; Biomarkers; Precision medicine; New treatment targets; Personalized medicine; Treatment targets
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2017.06.040

Despite the availability of more than 15 new “antiepileptic drugs”, the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20–30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood–brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. •Pharmacological interventions targeting the Zn2+–MTF1–CaV3.2 cascade may provide novel treatment approaches for drug-resistant TLE.•The innate immune system can mediate tissue remodeling, inducing epileptogenesis. This can be studied by cerebral microdialyis in models of TLE.•MiRNA-dependent regulation of synaptic plasticity is a widespread mechanism in epileptogenesis making miRNA suitable epilepsy-biomarkers.•Blood-brain barrier dysfunction may play a relevant role in epileptogenesis and vessel stabilization might be a valuable therapeutic target.•Tissuemodification by focal viral gene transfection or optogenetic interventions may play a role in future personalized epilepsy treatment.