Issues related to development of antiepileptogenic therapies

Epilepsia. 2013 Aug;54 Suppl 4(0 4):35-43. doi: 10.1111/epi.12297.

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.

Keywords: Disease modification; Epilepsy; Epileptogenesis; Preclinical; Protocol; Therapy.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Child
  • Chronic Disease
  • Controlled Clinical Trials as Topic
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Approval
  • Drug Discovery*
  • Drug Evaluation, Preclinical*
  • Drug Resistance
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / therapeutic use*
  • Evidence-Based Medicine
  • Humans
  • National Institute of Neurological Disorders and Stroke (U.S.)
  • United States

Substances

  • Anticonvulsants
  • Drugs, Investigational