Department of Neurosciences, Faculty of Medicine and Pharmacy, University of Mons, Ave. Champ de Mars 6, B-7000 Mons, Belgium.
Epilepsy Res. 2012 Feb;98(2-3):104-15. doi: 10.1016/j.eplepsyres.2011.10.006. Epub 2011 Nov 3.
Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs.
系统生物学（SB）是一种新兴的生物科学研究趋势，它从整体的角度来考虑生物系统中的复杂相互作用，将疾病视为相互作用网络的紊乱，而不是单个分子成分的改变。依赖于 SB 的网络药理学取代了传统的关注特定药物-受体相互作用和合理药物设计的“神奇子弹”，转而寻找多靶点药物，这些药物将作为“神奇猎枪”作用于生物网络。癫痫是一种多因素、多基因和动态的病理，因此 SB 方法似乎特别适合并有望用于抗癫痫药物（AED）的发现。事实上，早在 SB 出现之前，AED 的发现就已经涉及到一些类似 SB 的元素。一个报道的 SB 项目旨在发现癫痫的新药物靶点，它依赖于一个关系数据库，该数据库整合了临床信息、深部电极记录和 3D 大脑图像，以及大脑区域中特定基因表达修饰的组织学和分子生物学数据，这些区域显示出自发性癫痫活动。由于单一靶点并不能治疗复杂疾病，适当的药理学混杂可能会使 AED 具有多效性的优点。然而，多靶点药物发现需要复杂的任务来优化化合物的多种活性，同时必须平衡药物的性质并控制不良影响。这种新的药物发现方法的特定设计工具几乎没有出现，但是出现了能够可靠地进行多药理学计算预测的方法，而且它们的进展可能非常迅速。目前从还原论向网络药理学的转变，使得人们有望在 AED 发现中适当整合癫痫病理的内在复杂性，从而产生真正的抗癫痫药物。
