TY - JOUR
T1 - The challenge and promise of anti-epileptic therapy development in animal models
AU - Simonato, Michele
AU - Brooks-Kayal, Amy R.
AU - Engel, Jerome
AU - Galanopoulou, Aristea S.
AU - Jensen, Frances E.
AU - Moshé, Solomon L.
AU - O'Brien, Terence J.
AU - Pitkanen, Asla
AU - Wilcox, Karen S.
AU - French, Jacqueline A.
N1 - Funding Information:
JE has a patent pending for a magnetonanoparticle for functional MRI; JE has received no fees to date. (WO2009/123734A1 and WO2009/123735A1). ASG has received royalties from Morgan & Claypool Publishers and John Libbey Eurotext, and consultancy honorarium from Viropharma. FEJ has received investigator-initiated grant support from Eisai Pharma and Lundbeck Pharma. SLM has received consultancy honorarium from Lundbeck and UCB Pharma. TO'B has received research funding from Sanofi-Aventis, UCB, SciGen, GlaxoSmithKline, Novartis, and Janssen-Cilag, and speakers' honoraria from Sanofi-Aventis, UCB, SciGen, GlaxoSmithKline, and Janssen-Cilag. JAF is the president of The Epilepsy Study Consortium, a non-profit organisation; New York University (NYU) receives a fixed amount from the Epilepsy Study Consortium towards her salary. The money is for work by JAF on behalf of The Epilepsy Study Consortium, for consulting and clinical trial-related activities. She receives no personal income for these activities. Within the past year, The Epilepsy Study Consortium received payments for research services from: Acorda, Eisai Medical Research, GlaxoSmithKline, Impax, Johnson & Johnson, Mapp Pharmaceuticals, Marinus, Novartis, Lundbeck, Pfizer, Sepracor, Sunovion, SK Life Science, Supernus Pharmaceuticals, UCB/Schwarz Pharma, Upsher Smith, Vertex. JAF is an investigator at NYU on studies for Eisai Medical Research, LCGH, Impax, Mapp Pharmaceuticals, Novartis, UCB/Schwarz Pharma, Upsher Smith, and Vertex. MS, ARB-K, SLM, AP, and KSW declare no competing interests.
Funding Information:
The contents of this article are based on proposals made at a workshop of the Joint International League Against Epilepsy (ILAE) and American Epilepsy Society (AES) Translational Task Force to optimise and accelerate preclinical epilepsy research (London, UK, Sept 28–29, 2012). MS, ASG, TJO'B, and JAF organised the workshop. The work of this Task Force has received co-sponsorship from the ILAE, AES, Citizens United for Research in Epilepsy (CURE), Epilepsy Therapy Project, and Autism Speaks. The opinions expressed in this manuscript are ours and do not necessarily reflect the individual opinions of the workshop participants. We thank contributors to the Task Force for the wonderful discussions at the London workshop. We also thank Andrea Pizzirani for preparation of the figures before submission. MS has received funding from the European Community (FP7-PEOPLE-2011-IAPP project 285827 [EPIXCHANGE] and FP7-HEALTH project 602102 [EPITARGET]) and the Italian Ministry for Education, University and Research (PRIN 2010–11 project 2010N8PBAA [INBDNF]). ARB-K has received funding from the US National Institute of Neurological Disorders and Stroke (NINDS; R01NS38595; 1R21NS083057-02) and the US Department of Defense (W81XWH-11-1-0501). JE has received funding from the US National Institutes of Health (NIH; P01 NS02808, R01 NS33310, U01 NS42372, and P20 NS80181), AES, CURE, and the Epilepsy Therapy Project. ASG has received funding from NINDS (NS078333), CURE, Autism Speaks, the US Department of Defense (W81XWH-13-1-0180), and the Heffer Family and Segal Family Foundations. FEJ has received grants from NINDS (NS031718, NS 080268, NS-080565). SLM has received grants from NINDS (NS20253, NS43209, NS45911, NS78333), the US Department of Defense (W81XWH-13-1-0180), CURE, and the Heffer Family and Segal Family Foundations. TJO'B has received funding from the National Health and Medical Research Council, Australia (grants 1059858, 1059860, 1075117, 1017063, 1006077, and 1001206), and the Royal Melbourne Hospital Neuroscience Foundation. AP has received funding from the European Community (FP7-HEALTH project 602102 [EPITARGET]), the Academy of Finland (grant numbers 272249, 273909, 267199), the Sigrid Juselius Foundation, the European Science Foundation (EpiGENet), and ERA-NET Neuron II. KSW has received funding from NINDS (contract 271201100029C; grants NS078331 and NS065434). JAF has received funding from The Milken Foundation, the Epilepsy Research Foundation, and NINDS (2U01NS038455-11A1).
PY - 2014/9
Y1 - 2014/9
N2 - Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies-complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed.
AB - Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies-complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed.
UR - http://www.scopus.com/inward/record.url?scp=84906280998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906280998&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(14)70076-6
DO - 10.1016/S1474-4422(14)70076-6
M3 - Comment/debate
C2 - 25127174
AN - SCOPUS:84906280998
SN - 1474-4422
VL - 13
SP - 949
EP - 960
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 9
ER -