Identification of new epilepsy treatments: Issues in preclinical methodology

Authors

  • Aristea S. Galanopoulou,

    1. Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Montefiore/Einstein Epilepsy Management Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
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  • Paul S. Buckmaster,

    1. Departments of Comparative Medicine and Neurology and Neurological Sciences, Stanford University, Stanford, California, U.S.A.
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  • Kevin J. Staley,

    1. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • Solomon L. Moshé,

    1. Laboratory of Developmental Epilepsy, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Montefiore/Einstein Epilepsy Management Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
    2. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
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  • Emilio Perucca,

    1. Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, and National Neurological Institute IRCCS C. Mondino Foundation, Pavia, Italy
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  • Jerome Engel Jr,

    1. Departments of Neurology, Neurobiology, and Psychiatry & Behavioral Sciences and the Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
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  • Wolfgang Löscher,

    1. Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany
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  • Jeffrey L. Noebels,

    1. Department of Neurology, Baylor College of Medicine, Houston, Texas, U.S.A.
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  • Asla Pitkänen,

    1. Epilepsy Research Laboratory, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, and Department of Neurology, Kuopio University Hospital, Kuopio, Finland
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  • James Stables,

    1. Anticonvulsant Screening Program (ASP), NINDS, NIH, Bethesda, Maryland, U.S.A.
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  • H. Steve White,

    1. Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, U.S.A.
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  • Terence J. O’Brien,

    1. Departments of Medicine and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
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  • Michele Simonato for the American Epilepsy Society Basic Science Committee and the International League Against Epilepsy Working Group on Recommendations for Preclinical Epilepsy Drug Discovery

    1. Section of Pharmacology, Department of Clinical and Experimental Medicine, and Neuroscience Center, University of Ferrara, Ferrara, Italy, and National Institute of Neuroscience, Italy.
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Address correspondence to Aristea S. Galanopoulou, Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine,1410 Pelham Parkway South, Kennedy Center Rm 306, Bronx, NY 10461, U.S.A. E-mail: aristea.galanopoulou@einstein.yu.edu

Summary

Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities.

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