Portal de Periódicos da CAPES

Joint AES / ILAE translational workshop to optimize preclinical epilepsy research

2013; Wiley; Volume: 54; Issue: s4 Linguagem: Inglês

10.1111/epi.12293

1528-1167

Aristea S. Galanopoulou, Michele Simonato, Jacqueline A. French, Terence J. O’Brien,

Innovative Microfluidic and Catalytic Techniques Innovation

The articles in this supplement summarize the outcomes of a joint International League Against Epilepsy (ILAE) – American Epilepsy Society (AES) translational workshop to optimize and accelerate preclinical epilepsy therapy discovery that was held in Customs House Hotel, London, United Kingdom, on September 28–29, 2012. The workshop was attended by 49 international investigators, representing basic and clinical researchers, as well as representatives from the pharmaceutical industry, consumer organizations, and government research funders. The purpose of the workshop was to identify and recommend optimal methodologies, strategies, and infrastructure developments to accelerate and derisk the discovery, validation, and translation of preclinical discoveries into clinically successful therapies for seizures, epilepsies, and their comorbidities. The motivation behind this initiative was the realization that, despite the significant progress and the introduction of many antiseizure drugs into clinical practice, there are still major urgent needs to find treatments for drug-resistant seizures, as well as antiepileptogenic and disease-modifying therapies for epilepsies and their comorbidities. Therapy discovery and validation is associated with a staggering cost. The growing concern that a large number of preclinical discoveries fail to pass clinical testing, and that those that have passed have not substantially changed the number of patients with treatment resistant epilepsy, and have not made any inroads into disease modification or antiepileptogenesis, have raised the need for new strategies and methods to optimize and derisk the process of antiepilepsy therapy discovery. These issues were summarized in a recently published Joint AES/ILAE report (Galanopoulou et al., 2012). The joint ILAE/AES effort to address these issues progressed through the ongoing collaboration of two task forces: the Preclinical Epilepsy Drug Discovery Task Force of the ILAE Commission on Neurobiology and the AES Translational Task Force. In preparation for the London workshop, seven working subgroups were created to address specific topics through a series of teleconferences. At the workshop, each working subgroup presented its summary presentation and proposal, followed by a general discussion of all participants. Based on this discussion, each of the working groups has subsequently authored a paper highlighting the issues relevant to their topic and suggesting ways to progress the field forward. Working Group 1, chaired by Jacqueline French, outlined the common epilepsy syndromes that present clinical "gaps to care" and/or provide opportunities to test new therapies, and discussed whether the existing animal models and preclinical behavioral tests may predict a drug's efficacy and tolerability in human patients. Working Group 2, chaired by Aristea Galanopoulou, addressed technical and methodologic issues related to the conduct and reporting of preclinical antiepilepsy therapy studies, the regulatory requirements that need to be addressed, and improvements in the infrastructure that would optimize and accelerate these studies. Working Group 3, chaired by Karen Wilcox, discussed the specific challenges in the identification and validation of treatments for drug-resistant seizures. Working Group 4, chaired by Asla Pitkänen, proposed strategies for optimizing preclinical antiepileptogenesis studies, and discussed the challenges and the possible opportunities to achieve these goals. Working Group 5, chaired by Amy Brooks-Kayal, dealt with the complex interactions between epilepsies and comorbidities, summarized the current state of preclinical testing for anticomorbidity treatments, and proposed initiatives that may optimize this process. Working Group 6, chaired by Jerome (Pete) Engel Jr, identified the needs and strategies for the discovery and validation of biomarkers for epileptogenicity, epileptogenesis, and pharmacoresistance. Working Group 7, chaired by Michele Simonato and Terence O'Brien, presented a proposal for multicenter preclinical trials and criteria to select candidate therapies for transition to clinical testing. At the end of the workshop, to carve a roadmap to achieve the goals, a panel discussion was planned to set priorities, goals, and next steps. Panelists included representatives of the sponsors of the London workshop, Nico Moshé (ILAE), Frances Jensen (AES), Steve White (Citizens United for Research in Epilepsy, CURE), Roger Porter (Epilepsy Therapy Project), and Daniel Smith (Autism Speaks); Vicky Whittemore as a representative of the National Institute of Neurological Disorders and Stroke (NINDS); as well as two international investigators involved in antiepilepsy therapy discovery, Emilio Perucca and Terence O'Brien. The outcome of the meeting was the consensus on the long-term goals (vision) and on the immediate initiatives (five primary next steps) to be undertaken. It was noted that achieving the first goal may also address the other two. The workshop was organized by Jackie French, Aristea Galanopoulou, Terence O'Brien, and Michele Simonato, and was made possible through the generous co-sponsorship by the ILAE, AES, CURE, Epilepsy Therapy Project, and Autism Speaks. The active participation of Drs Whittemore, Fureman, and Ranganathan was also valuable in interfacing with the parallel initiatives from NINDS. Other contributors to the working groups included the following: Alexis Arzimanoglou, Kevin Bath, Elinor Ben-Menachem, Ann Berg, Edward H. Bertram III, Amy Brooks-Kayal, Jim Cloyd, Andrew Cole, Stephen Collins, Mark Dichter, Tracy Dixon-Salazar, Ed Dudek, Jerome Engel Jr., Dan Friedman, Brandy Fureman, Greg Holmes, John Huguenard, Frances Jensen, Rafal Kaminski, Andres Kanner, Jaideep Kapur, Henrik Klitgaard, Merab Kokaia, Holger Lerche, Jeffrey Loeb, Wolfgang Loescher, John Messenheimer, Istvan Mody, Solomon L. Moshé, Astrid Nehlig, Jeffrey L. Noebels, Manisha Patel, Emilio Perucca, Asla Pitkanen, Roger Porter, Michael Privitera, Jong Rho, Robert Ring, Michael Rogawski, Dieter Schmidt, Graeme Sills, Daniel Smith, Helen Scharfman, Kevin Staley, Eugene Trinka, Elisabetta Vaudano, Annamaria Vezzani, Matthew Walker, Steve H. White, Samuel Wiebe, and Karen S. Wilcox. A briefer version of this workshop summary was included in the ILAE Epigraph: http://www.ilae.org/Visitors/Publications/Fall_winter2012.cfm. TOB has received research grant support from the NHMRC (Australia), the Royal Melbourne Hospital Neuroscience Foundation, Sanofi-Aventis, UCB, SciGen, GlaxoSmithKline, Novartis and Janssen-Cilag, and speaker honorarium from Sanofi-Aventis, UCB, SciGen, Glaxo-Smith-Kline, and Janssen-Cilag. HK is an employee at UCB Pharma. MS has received research funding from the European Union (Epixchange), the Italian Ministry for Research and the University (Prin 2010-11), GlaxoSmithKline, Chiesi Pharmaceuticals (Italy), Sanofi-Synthelabo, and Schering-Plough. ASG has received research grant support from NINDS (NS078333 and NS020253), Autism Speaks, CURE, and the Heffer and Siegel Families Foundations. ASG has received speaker honorarium from Novartis and royalties from Morgan and Claypool Publishers and John Libbey Eurotext. JF serves as the President of The Epilepsy Study Consortium, a nonprofit organization. NYU, where Dr. French is employed, receives a fixed amount from the Epilepsy Study Consortium toward Dr. French's salary. The money is for work performed by Dr. French on behalf of The Epilepsy Study Consortium, for consulting and clinical trial related activities. Dr. French receives no personal income for these activities. Within the past year, The Epilepsy Study Consortium received payments from the following: Cyberonics, Eisai Medical Research, EntraPharmaceuticals, GlaxoSmithKline, Icagen, Inc., Johnson & Johnson, Marinus, Neurotherapeutics, NeuroVista Corporation, Ono Pharma U.S.A., Inc., Lundbeck, Pfizer, Sepracor, Sunovion, SK Life Science, Supernus Pharmaceuticals, UCB Inc/Schwarz Pharma, Upsher Smith, Valeant, and Vertex. JF also received funding from NINDS, Milken Foundation, and the Epilepsy Therapy Project. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.