Precision medicine in genetic epilepsies: break of dawn?

ABSTRACT

Introduction: Therapy with current antiepileptic drugs aims at reducing the likelihood of seizure occurrence rather than influencing the underlying disease process. Therefore, antiepileptic drugs have an anticonvulsant rather than antiepileptic property.

Areas covered: The increasing identification of genetic causes for epilepsy over the recent years improves the understanding of the underlying epileptogenic process and allows for the possibility of directed therapeutic approaches. An ideal antiepileptic therapy consists of a drug which is able to influence the functional changes caused by a specific pathogenic variant. In this review we will describe the current precision medicine approaches in genetic epilepsies in reference to the identified genetic etiologies. References for this review were identified through searches of PubMed and the authors’ own files.

Expert commentary: Currently established or investigated precision medicine treatments include the ketogenic diet in patients with GLUT1 deficiency, sodium channel blockers in patients with KCNQ2, SCN2A and SCN8A mutations as well as mTOR-inhibitors in mTORopathies. These predominantly represent already available treatments that were repurposed for use in epilepsy. The development of new therapeutic agents aiming at targets identified in genetic epilepsies will advance epilepsy treatment considerably.

KEYWORDS:

• Epilepsy genetics
• precision medicine
• personalized medicine
• translational epilepsy research

Declaration of interest

P.S. Reif reports a grant from the P.E. Kempkes foundation Marburg. M.H. Tsai reports personal fees from Eisai, GSK, Eli Lilly, Sanofi, Medtronic, Novartis, Takeda and UCB, Taiwan. I. Helbig was supported by intramural funds of the University of Kiel, by a grant from the Deutsche Forschungsgemeinschaft (HE5415/3-1) within the EuroEPINOMICS framework of the European Science Foundation and grants of the Deutsche Forschungsgemeinschaft (DFG, HE5415/5-1, HE5415/6-1), Bundesministerium für Bildung und Forschung (01DH12033, MAR 10/012), and by the German chapter of the International League against Epilepsy (DGfE). He has also received support through the International League Against Epilepsy (ILAE) within the Epilepsiome initiative of the ILAE Genetics Commission (www.channelopathist.net). K.M. Klein reports personal fees from UCB Pharma, Novartis Pharma AG and Eisai as well as grants from the Deutsche Forschungsgemeinschaft and The University of Melbourne. F. Rosenow reports personal fees from Eisai, grants and personal fees from UCB, grants and personal fees from Desitin Pharma, personal fees and other from Novartis, personal fees from Medronic, personal fees from Cerbomed,personal fees from ViroPharma and Shire, grants from European Union, grants from Deutsche Forschungsgemeinschaft. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The contributions of K.M. Klein and F. Rosenow were supported by the European Union’s ‘Seventh Framework’ Programme (FP7) under the Epimirna Grant Agreement no. 602130 (www.epimirna.eu) and the Detlev-Wrobel-Fonds for Epilepsy Research Frankfurt.