Prevention and Cure How to achieve the goal European perspective*

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1 The rollercoaster perspective of epilepsy Prevention and Cure How to achieve the goal European perspective* Professor Dieter Schmidt Epilepsy Research Group Berlin *1 in 26 individuals will have epilepsy at some point in their lifetime a. Epilepsy is like a rollercoaster. a (Institute of Medicine. 2012).

2 Roadmap: How to achieve the goal Prevention of epileptogenic brain injury Discovery and preclinical development of antiepileptogenic drugs (AEG) Innovative clinical AEG trial design Summary and Conclusions

3 Roadmap: How to achieve the goal Prevention of epileptogenic brain injury Discovery and preclinical development of antiepileptogenic drugs (AEG) Innovative clinical AEG trial design Summary and Conclusions

4 Epilepsies of unknown etiology Symptomatic Epilepsies TBI WANTED: Biomarkers Prevention Disease modification Stroke ICH Tumor Infection Genetic Epilepsies Prevent insult Prevent epileptogenesis during latent period Don t miss the therapeutic window! Disease modification (mod. French et al, 2013) Pre-Symptomatic First seizure Epilepsy

5 Roadmap: How to achieve the goal Prevention of epileptogenic brain injury Discovery and preclinical development of antiepileptogenic drugs (AEG) Innovative clinical AEG trial design Summary and Conclusions

6 Prevention of epilepsy: animal model AEG = antiepileptogenic (Blumenfeld et al 2008) Control AEG Issues: Control: Active drug? Epilepsy model? Counting seizures? Antiseizure

7 Roadmap: How to achieve the goal Prevention of epileptogenic brain injury Discovery and preclinical development of antiepileptogenic drugs (AEG) Innovative clinical AEG trial design Summary and Conclusions

8 % without seizure Prevention: Clinical proof-of-concept(target) trial Epileptogenic insult (Schmidt and Friedmann, 2012) treatment Observation period 100% Antiepileptogenic drug effect (AEG) Video-EEG monitoring week Issues: Controls-active drug? Issues: Biomarkers Issues: Remote seizure count? Antiseizure drug effect

9 Opportunities for disease modification: natural history of treated new-onset epilepsy 37 years of follow-up from the first seizure on 48% Terminal remission from the start 19% Late remission (Relapsing-remitting course) = 67% Good outcome with terminal remission 14% Worsening course (Remitting-relapsing) 19% Drug resistant epilepsy from the start = 33% Poor outcome without remission (Sillanpää and Schmidt, Brain, 2006)

10 % seizure Disease modification: Clinical proof-of-concept(target) trial Epileptogenic insult Observation period treatment 100% (Schmidt and Friedmann, 2012) Antiepileptogenic effect Antiseizure effect 0% Baseline AED Video-EEG monitoring Issues: Control by active drug? Issues: Biomarkers? Issues: Remote seizure count? weeks

11 European Study of Epilepsy Prevention (ESEP) and Disease Modification (ESDM) Prevent insult: stroke, cancer, injury etc Prevent epilepsy in latent period Comparative preclinical and clinical proof of concept (target) studies of antiepileptogenic drugs using biomarkers for the risk of epilepsy Prevent epilepsy after first seizure (Disease modification) Comparative preclinical and clinical proof of concept (target) studies of antiepileptogenic drugs using biomarkers for the risk of worsening of epilepsy Identify better methods to follow the course of epilepsy

12 European Study of Epilepsy Cure (ESEC) Prevent or control drug resistant epilepsy Prevent or control relapse following remission on AEDs and off AEDs Prevent or control relapse following surgical remission on and off AEDs

13 Cure of childhood-onset epilepsy: now C( Cure = sustained remission off AEDs = 81/90 (90%)

14 % of Patients Surgical cure: Seizure free off AEDs after temporal lobe surgery Kelley and Theodore year (48) 5 years (48) 10 years (48) 30 years (45) SF no AEDs SF on AEDs NSF dead 104 of 365 (28%) seizure-free adults had discontinued AEDs after epilepsy surgery (de Tisi et al. 2011)

15 Roadmap: How to achieve the goal Prevention of epileptogenic brain injury Discovery and preclinical development of antiepileptogenic drugs (AEG) Innovative clinical AEG trial design Summary and Conclusions

16 Roadmap: How to achieve the goal of prevention and cure of epilepsy Establish a European Consortium for Prevention of Epilepsy Studies: preclinical and clinical Establish a European Consortium for Cure and Disease Modification of Epilepsy Studies: preclinical and clinical Support target-driven discovery and development of antiepileptogenic drugs (AEG) Support innovative clinical AEG trial design