title: Issues related to development of antiepileptogenic therapies.
abstract: Several preclinical proof-of-concept studies have provided evidence for positive treatment effects on epileptogenesis. However, none of these hypothetical treatments has advanced to the clinic. The experience in other fields of neurology such as stroke, Alzheimer's disease, or amyotrophic lateral sclerosis has indicated several problems in the design of preclinical studies, which likely contribute to failures in translating the positive preclinical data to the clinic. The Working Group on "Issues related to development of antiepileptogenic therapies" of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) has considered the possible problems that arise when moving from proof-of-concept antiepileptogenesis (AEG) studies to preclinical AEG trials, and eventually to clinical AEG trials. This article summarizes the discussions and provides recommendations on how to design a preclinical AEG monotherapy trial in adult animals. We specifically address study design, animal and model selection, number of studies needed, issues related to administration of the treatment, outcome measures, statistics, and reporting. In addition, we give recommendations for future actions to advance the preclinical AEG testing.
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. asla.pitkanen@uef.fi
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
authors.forename: Amy R
authors.initials: AR
authors.lastname: Brooks-Kayal
authors.forename: F Edward
authors.initials: FE
authors.lastname: Dudek
authors.forename: Daniel
authors.initials: D
authors.lastname: Friedman
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
authors.forename: Rafal M
authors.initials: RM
authors.lastname: Kaminski
authors.forename: Jaideep
authors.initials: J
authors.lastname: Kapur
authors.forename: Henrik
authors.initials: H
authors.lastname: Klitgaard
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
authors.forename: Istvan
authors.initials: I
authors.lastname: Mody
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002908:Chronic Disease; D018849:Controlled Clinical Trials as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006801:Humans; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D014481:United States
chemical_list: D000927:Anticonvulsants; D015507:Drugs, Investigational
keywords: Disease modification; Epilepsy; Epileptogenesis; Preclinical; Protocol; Therapy
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