Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, 417 Wakara Way, Suite 3211, Salt Lake City, UT, 84108, USA,
Drugs. 2015 May;75(7):749-67. doi: 10.1007/s40265-015-0395-9.
Several relevant animal models of epileptogenesis and biomarkers have emerged for evaluating the antiepileptogenic potential of an investigational drug. Although several promising candidate compounds and approaches have been identified in these preclinical models, no treatment has yet successfully navigated the path from preclinical efficacy to clinical validation. Until such an agent can move from preclinical proof of concept to clinical success, the need remains to continually develop and optimize preclinical models and clinical trial design in an effort to guide potential clinical investigations. This review describes several available models of disease modification and/or epileptogenesis, preclinical studies in these models and potential biomarkers useful for evaluating the efficacy of a potential therapeutic agent in the preclinical setting. The results that emerge from such efforts may then guide the clinical evaluation of a candidate compound. This review discusses some of the known limitations and hurdles to moving compounds found effective in these models to clinical practice, in the hope that knowledge of this information will facilitate the design and conduct of clinical studies and effectively facilitate the identification of a first-in-class disease-modifying or antiepileptogenic agent.
已经出现了几种与癫痫发生相关的动物模型和生物标志物，可用于评估研究药物的抗癫痫发生潜力。尽管在这些临床前模型中已经确定了几种有前途的候选化合物和方法，但没有一种治疗方法能够成功地从临床前疗效验证过渡到临床验证。在这种药物能够从临床前概念验证转变为临床成功之前，仍然需要不断开发和优化临床前模型和临床试验设计，以指导潜在的临床研究。这篇综述描述了几种可用的疾病修饰和/或癫痫发生模型，以及这些模型中的临床前研究和潜在的生物标志物，这些标志物可用于评估潜在治疗药物在临床前环境中的疗效。这些努力得出的结果可能会指导候选化合物的临床评估。本文讨论了将在这些模型中发现有效的化合物推向临床实践所面临的一些已知限制和障碍，希望了解这些信息将有助于临床研究的设计和实施，并有效地促进发现一类新型的疾病修饰或抗癫痫发生药物。
