Balestrini Simona, Sisodiya Sanjay M
NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, and Epilepsy Society, Chalfont-St-Peter, Bucks, United Kingdom; Neuroscience Department, Polytechnic University of Marche, Ancona, Italy.
NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, and Epilepsy Society, Chalfont-St-Peter, Bucks, United Kingdom.
Neurosci Lett. 2018 Feb 22;667:27-39. doi: 10.1016/j.neulet.2017.01.014. Epub 2017 Jan 10.
There is high variability in the response to antiepileptic treatment across people with epilepsy. Genetic factors significantly contribute to such variability. Recent advances in the genetics and neurobiology of the epilepsies are establishing the basis for a new era in the treatment of epilepsy, focused on each individual and their specific epilepsy. Variation in response to antiepileptic drug treatment may arise from genetic variation in a range of gene categories, including genes affecting drug pharmacokinetics, and drug pharmacodynamics, but also genes held to actually cause the epilepsy itself. From a purely pharmacogenetic perspective, there are few robust genetic findings with established evidence in epilepsy. Many findings are still controversial with anecdotal or less secure evidence and need further validation, e.g. variation in genes for transporter systems and antiepileptic drug targets. The increasing use of genetic sequencing and the results of large-scale collaborative projects may soon expand the established evidence. Precision medicine treatments represent a growing area of interest, focussing on reversing or circumventing the pathophysiological effects of specific gene mutations. This could lead to a dramatic improvement of the effectiveness and safety of epilepsy treatments, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Whilst much has been written about epilepsy pharmacogenetics, there does now seem to be building momentum that promises to deliver results of use in clinic.
癫痫患者对抗癫痫治疗的反应存在很大差异。遗传因素对这种差异有显著影响。癫痫遗传学和神经生物学的最新进展正在为癫痫治疗的新时代奠定基础，该时代聚焦于每个个体及其特定的癫痫类型。对抗癫痫药物治疗反应的差异可能源于一系列基因类别的遗传变异，包括影响药物药代动力学和药效学的基因，以及实际上导致癫痫本身的基因。从纯粹的药物遗传学角度来看，在癫痫领域几乎没有确凿证据支持的可靠遗传发现。许多发现仍存在争议，证据多为轶事性或不太可靠的，需要进一步验证，例如转运体系统基因和抗癫痫药物靶点的变异。基因测序的日益广泛应用以及大规模合作项目的结果可能很快会扩大已有的证据。精准医学治疗是一个越来越受关注的领域，专注于逆转或规避特定基因突变的病理生理效应。通过针对每个特定个体中导致癫痫的生物学机制，这可能会显著提高癫痫治疗的有效性和安全性。虽然关于癫痫药物遗传学已经有很多著述，但现在似乎确实有越来越多的势头，有望产生可用于临床的结果。
