Identification of new epilepsy treatments: issues in preclinical methodology.

Abstract

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.

• Authors: Aristea S Galanopoulou, Paul S Buckmaster, Kevin J Staley, Solomon L Moshé, Emilio Perucca, Jerome Engel Jr, Wolfgang Löscher, Jeffrey L Noebels, Asla Pitkänen, James Stables, H Steve White, Terence J O'Brien, Michele Simonato, American Epilepsy Society Basic Science Committee And The International League Against Epilepsy Working Group On Recommendations For Preclinical Epilepsy Drug Discovery
• Journal: Epilepsia (Epilepsia) Vol. 53 Issue 3 Pg. 571-82 (Mar 2012) ISSN: 1528-1167 [Electronic] United States
• PMID: 22292566 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Chemical References

• Anticonvulsants

Topics

• Animals
• Anticonvulsants (isolation & purification, pharmacology)
• Comorbidity (trends)
• Disease Models, Animal
• Drug Evaluation, Preclinical (methods, standards, trends)
• Drug Resistance (physiology)
• Epilepsy (drug therapy, epidemiology)
• Humans
• Translational Research, Biomedical (methods, standards, trends)