Identification of new epilepsy treatments: Issues in preclinical methodology
Identification of new epilepsy treatments: Issues in preclinical methodology
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DOI：
10.1111/j.1528-1167.2011.03391.x
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发表时间：
2012-03-01
期刊：
影响因子：
5.6
通讯作者：
Simonato, Michele
中科院分区：
文献类型：
--
作者：
Galanopoulou, Aristea S.;Buckmaster, Paul S.;Simonato, Michele
临床前研究促进了发现有价值的药物用于癫痫的对症治疗。然而，尽管有这些治疗，癫痫发作在三分之一的受影响个体中没有得到充分控制，并且合并症仍然对生活质量造成重大负担。在过去的二十年里，多种新疗法的引入并没有改变这一点。迫切需要解决以下未满足的临床需求：（1）具有改善疗效/耐受性特征的耐药性癫痫发作的新对症抗癫痫治疗，（2）预防或改善癫痫发生过程的疾病改善治疗，以及（3）导致癫痫患者残疾的常见合并症的治疗。新疗法还需要满足某些亚群的特殊需求，即针对年龄或性别的治疗。由于表现和病因的异质性，这些治疗领域的临床前开发很复杂，可能需要根据特定的癫痫发作、癫痫综合征或合并症进行制定。本报告的目的是提供一个框架，将有助于定义未来的指南，以改善和标准化的设计，报告和验证数据的临床前抗癫痫治疗开发研究，针对耐药性癫痫发作，癫痫发生和合并症。
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.