title: Systems biology impact on antiepileptic drug discovery.
abstract: 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.
authors: Department of Neurosciences, Faculty of Medicine and Pharmacy, University of Mons, Ave. Champ de Mars 6, B-7000 Mons, Belgium. doru.margineanu@skynet.be
authors: Doru Georg
authors: DG
authors: Margineanu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D049490:Systems Biology
chemical_list: D000927:Anticonvulsants