WORKSHOP REPORT WONOEP XI: Workshop summary by the Scientific Organizing Committee The Workshop on Neurobiology of the Epilepsies (WONOEP), a satellite event of the ILAE Congress since 1989, represents an important biannual arena for discussion of issues related to experimental epileptology. The eleventh edition of WONOEP (Villa Grazioli, Grottaferrata, Italy; August 24–27, 2011) focused on Finding a better drug for epilepsy. A new workshop format proposed by an ad hoc Task Force of the Neurobiology Commission was success- fully tested. Among the key changes was an emphasis on par- ticipation of young independent scientists with a solid and original approach to preclinical research on neurobiology of epilepsy. During the 3-day meeting, four panel sessions were organized on specific topics related to the main theme: Panel Session I—Preclinical screening strategies and experimental trial design. Panel Session II—Antiepileptogenesis targets. Panel Session III—Antiinflammatory targets. Panel Session IV—Channels, synapses, receptors, and ions as new targets. The goal of the first panel on preclinical screening strat- egies and experimental trial design was to consider the need for improved preclinical screening strategies to iden- tify antiepileptic drugs (AEDs) that target unmet medical needs with respect to drug-refractory epilepsies. New tech- nologies should be adopted to develop medium- to high- throughput screening preclinical models. One option is to perform in vivo AED testing in relevant models mimicking different aspects of drug refractory epilepsy and/or epileptogenesis, guided by the expression of relevant bio- markers of ictogenesis and/or epileptogenesis. This proof- of-concept approach should help confirm preclinical findings, thereby facilitating clinical testing and lowering the risk of the overall development effort. The session on antiepileptogenic targets, broadly inclu- sive of the current state of research activity in this area of experimental therapeutics, discussed both older and newer molecular targets within innovative and thought-provok- ing therapeutic frameworks. Glutamate receptors, throm- bospondin receptors, epigenetic regulation, granular ‘‘hub’’ cells, magnetic resonance imaging, neurotrophic factors, erythropoietin-derived peptide mimetics, ketogen- ic diet, and bumetanide derivatives were revisited and reevaluated, with a goal of weaving the seemingly unre- lated topics into a common ‘‘neurometabolic’’ fabric. A panel on antiinflammatory targets focused on the analysis of distinct signal-transduction inflammatory path- ways involved in the epileptogenic process. The contribu- tion of specific inflammatory molecules to the progression of both epilepsy and epilepsy-related morbidities, and the multifaceted roles of inflammatory mediators in ictogene- sis and epileptogenesis, are discussed. These complexities highlight the current challenge to define inflammatory molecules as promising targets for epilepsy prevention and treatment. A subpanel of the inflammatory targets session focused on the mammalian target of rapamycin (mTOR) pathway as a potential antiepileptogenic target for future epilepsy treatment. The mTOR pathway regulates cell growth, differentiation, proliferation, and metabolism; dysregulation of the pathway has been implicated in sev- eral genetic and acquired forms of epilepsy/epileptogene- sis. Loss-of-function mutations in upstream mTOR regulators are associated with epileptic syndromes, such as tuberous sclerosis and Cowden disease. Preclinical studies suggest that inhibition of mTOR pathway prevents epi- lepsy and improves underlying pathology in mouse models of these diseases and in post–status epilepticus models of temporal lobe epilepsy, although these effects depend upon the timing and dose of administration. Panel session IV addressed the usefulness of targeting specific molecular pathways in preventing/delaying epile- ptogenesis or in improving seizure control. Epileptogene- sis is associated with multiple molecular modifications at the level of channels, synapses, receptors, and ion trans- porters, and it is therefore difficult to establish causality between a given modification and epileptogenesis. One approach to this problem is to identify general upstream mechanisms responsible for large network modifications. Another possibility is to target general pathways that will affect network activities. The validation of both approaches is determined by a key functional readout—the disease-modifying effect of the manipulation/treatment. The study of human tissue and its value for the understand- ing of ictogenesis and the identification of potential targets was also discussed in this session. Each panel was introduced by a keynote speaker and included data presentations and extensive discussion. The proceedings of the workshop will be summarized in five review articles planned for publication this year. The first two WONOEP appraisals (on ‘‘antiinflammatory targets’’ and ‘‘the mTOR pathway’’) are published in the current issue of Epilepsia. WONOEP XI was sponsored by International League Against Epilepsy Commission on Neurobiology, and was GRAY M ATTERS 1275