Using common genetic variants to find drugs for common epilepsies

• DOI: 10.1093/braincomms/fcab287
• Publication Date: 2021-12-01T04:29:58Z
• Authors: Nasir Mirza; Remi Stevelink; Basel Taweel; Bobby P C Koeleman; Anthony G Marson; ; Bassel Abou-Khalil; Pauls Auce; Andreja Avbersek; Melanie Bahlo; David J Balding; Thomas Bast; Larry Baum; Albert J Becker; Felicitas Becker ...; Samuel F Berkovic; Katja E Boysen; Jonathan P Bradfield; Lawrence C Brody; Russell J Buono; Ellen Campbell; Gregory D Cascino; Claudia B Catarino; Gianpiero L Caval...; Stacey S Cherny; Krishna Chinthapalli; Alison J Coffey; Alastair Compston; Antonietta Coppola; Patrick Cossette; John J Craig; Gerrit-Jan de Haan; Peter De Jonghe; Carolien G. F de ...; Norman Delanty; Chantal Depondt; Orrin Devinsky; Dennis J Dlugos; Colin P Doherty; Christian E Elger; Johan G Eriksson; Thomas N Ferraro; Martha Feucht; Ben Francis; Andre Franke; Jacqueline A French; Saskia Freytag; Verena Gaus; Eric B Geller; Christian Gieger; Tracy Glauser; Simon Glynn; David B Goldstein; Hongsheng Gui; Youling Guo; Kevin F Haas; Hakon Hakonarson; Kerstin Hallmann; Sheryl Haut; Erin L Heinzen; Ingo Helbig; Christian Hengsbach; Helle Hjalgrim; Michele Iacomino; Andrés Ingason; Jennifer Jamnadas...; Michael R Johnson; Reetta Kälviäinen; Anne-Mari Kantanen; Dalia Kasperavičiūte; Dorothee Kastelei...; Heidi E Kirsch; Robert C Knowlton; Bobby P. C Koeleman; Roland Krause; Martin Krenn; Wolfram S Kunz; Ruben Kuzniecky; Patrick Kwan; Dennis Lal; Yu-Lung Lau; Holger Lerche; Costin Leu; Wolfgang Lieb; Dick Lindhout; Warren D Lo; Iscia Lopes-Cendes; Daniel H Lowenstein; Alberto Malovini; Anthony G Marson; Thomas Mayer; Mark McCormack; James L Mills; Nasir Mirza; Martina Moerzinger; Rikke S Møller; Anne M Molloy; Hiltrud Muhle; Mark Newton; Ping-Wing Ng; Markus M Nöthen; Peter Nürnberg; Terence J O’Brien; Karen L Oliver; Aarno Palotie; Faith Pangilinan; Sarah Peter; Slavé Petrovski; Annapurna Poduri; Michael Privitera; Rodney Radtke; Sarah Rau; Philipp S Reif; Eva M Reinthaler; Felix Rosenow; Josemir W Sander; Thomas Sander; Theresa Scattergood; Steven C Schachter; Christoph J Schankin; Ingrid E Scheffer; Bettina Schmitz; Susanne Schoch; Pak C Sham; Jerry J Shih; Graeme J Sills; Sanjay M Sisodiya; Lisa Slattery; Alexander Smith; David F Smith; Michael C Smith; Philip E Smith; Anja C. M Sonsma; Doug Speed; Michael R Sperling; Bernhard J Steinhoff; Ulrich Stephani; Remi Stevelink; Konstantin Strauch; Pasquale Striano; Hans Stroink; Rainer Surges; K. Meng Tan; Liu Lin Thio; G. Neil Thomas; Marian Todaro; Rossana Tozzi; Maria S Vari; Eileen P. G Vining; Frank Visscher; Sarah von Spiczak; Nicole M Walley; Yvonne G Weber; Zhi Wei; Judith Weisenberg; Christopher D Whelan; Peter Widdess-Walsh; Markus Wolff; Stefan Wolking; Wanling Yang; Federico Zara; Fritz Zimprich
• Keywords: Drug repositioning; Repurposing; Drug Development; Efficacy

Abstract Better drugs are needed for common epilepsies. Drug repurposing offers the potential of significant savings in time and cost developing new treatments. In order to select best candidate drug(s) repurpose a disease, it is desirable predict relative clinical efficacy that will have against disease. Common epilepsy can be divided into different types syndromes. Different antiseizure medications most effective syndromes epilepsy. For predictions antiepileptic clinically translatable, essential specific each form epilepsy, reflect patterns drug observed studies practice. These requirements not fulfilled by previously published We developed novel method predicting any using its Genome-Wide Association Study summary statistics drugs’ activity data. The methodological advancement our technique disease based upon effects on function abundance proteins, magnitude direction those effects, importance, degree proteins’ dysregulation used this all drugs, licensed condition, major Our concordant with findings from real-world experience randomized trials. predicts existing epilepsies; prediction, outperforms alternative method: area under receiver operating characteristic curve (mean ± standard deviation) 0.83 0.03 0.63 0.04, respectively. Importantly, which amongst more efficacious practice, less main distinct individual trials identify promising screen five predicted an animal model: exerts dose-dependent effect seizures. resource selecting suitable could potentially repurposed generalizable other complex diseases.