An integrated systems-level framework for deciphering multidrug resistant epilepsy.

癫痫是一种严重的、常见的神经系统疾病——每26个人中就有一人会在一生中的某个阶段患上癫痫。癫痫具有巨大的公共卫生意义——在世界卫生组织的疾病致残排名中，癫痫是第五大致残疾病，仅在英国国家医疗服务体系（NHS）的急诊人数中，癫痫就占了3%。最大的负担落在20-30%的癫痫患者身上，尽管目前有所有可用的抗癫痫药物，他们的癫痫发作仍然无法控制。这些人的死亡风险以及癫痫的其他并发症（如记忆和认知困难）以及疲劳和失业的风险显著增加。令人惊讶的是，在过去50年的抗癫痫药物开发中，在改善癫痫发作控制方面没有取得任何进展，目前的抗癫痫药物都没有改善或治愈疾病的作用。尽管进行了数十年的研究，但仍未取得进展，这要求我们采取一种新的科学方法。我们的项目汇集了英国三所顶尖大学（帝国理工学院、伦敦大学学院、剑桥大学），将数据和专业知识结合起来，以解决这一未被满足的主要临床需求。我们的目标很远大——找到更好的治疗癫痫的药物。我们的项目结合了世界上最大和最全面的癫痫药物反应基因数据集，以及经过验证的“大数据”计算方法，用于研究基因如何相互作用导致疾病。然后，利用最新的方法将疾病机制与药物靶点联系起来，我们的目标是将这些见解转化为耐药性癫痫患者的新疗法。我们的项目有可能改变耐药癫痫患者的生活，并为健康和疾病中人类大脑功能的基本机制提供信息。

Epilepsy is a serious, common neurological disease - one in 26 people will develop epilepsy at some point in their life. Epilepsy has huge public health significance - it is the 5th most disabling disease in the World Health Organisation's rankings of disability by illness and accounts for 3% of all A&E attendances in the UK NHS alone. The greatest burden falls on the 20-30% of people with epilepsy who continue to have uncontrolled seizures despite all currently available antiepileptic drugs. These people are at a significantly increased risk of dying, as well as from other complications of their epilepsy such as memory and cognitive difficulties, and under and unemployment. Surprisingly, there has been no progress in improving seizure control in the last 50 years of anti-epileptic drug development, and none of the current antiepileptic drugs are disease modifying or curative. This absence of progress despite decades of research mandates a new scientific approach. Our project brings together three leading universities in the UK (Imperial College, University College London, Cambridge University) to combine data and expertise in order to address this major unmet clinical need. Our goal is ambitious - to find better drugs for treating epilepsy. Our project combines the largest and most comprehensive genetic datasets on drug response in epilepsy worldwide with proven "big-data" computational methods for working out how genes interact with each other to cause disease. Then, using the latest methods to connect disease mechanisms to drug targets, we aim to translate these insights to new therapies for people living with drug resistant epilepsy. Our project has the potential to transform the lives of people with drug resistant epilepsy, and to inform fundamental mechanisms of human brain function in health and disease generally.