Brazilian Biosciences National Laboratory (LNBio), Center for Research in Energy and Material (CNPEM), Campinas, SP, Brazil.
Laboratory of Embryonic Genetic Regulation, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Curr Neuropharmacol. 2021;19(6):813-831. doi: 10.2174/1570159X18666200915151909.
Epilepsy is the most common chronic neurologic disorder in the world, affecting 1-2% of the population. Besides, 30% of epilepsy patients are drug-resistant. Genomic mutations seem to play a key role in its etiology and knowledge of strong effect mutations in protein structures might improve prediction and the development of efficacious drugs to treat epilepsy. Several genetic association studies have been undertaken to examine the effect of a range of candidate genes for resistance. Although, few studies have explored the effect of the mutations into protein structure and biophysics in the epilepsy field. Much work remains to be done, but the plans made for exciting developments will hold therapeutic potential for patients with drug-resistance. In summary, we provide a critical review of the perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in light of core elements such as transcriptomics, structural biology, disease model, pharmacogenomics and pharmacokinetics in a manner to improve the success of trial designs of antiepileptic drugs.
癫痫是世界上最常见的慢性神经系统疾病，影响全球 1-2%的人口。此外，30%的癫痫患者对药物治疗无效。基因组突变似乎在其发病机制中起关键作用，对蛋白质结构中强效应突变的了解可能会改善对癫痫的预测和有效治疗药物的开发。已经进行了几项遗传关联研究，以检查一系列候选耐药基因的作用。然而，在癫痫领域，很少有研究探索突变对蛋白质结构和生物物理学的影响。仍有许多工作要做，但为令人兴奋的发展制定的计划将为耐药患者提供治疗潜力。总之，我们根据转录组学、结构生物学、疾病模型、药物基因组学和药代动力学等核心要素，对基于遗传多态性/突变的癫痫个体化医学的发展前景进行了批判性评估，以提高抗癫痫药物试验设计的成功率。
