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Observational Study
. 2021 Oct;92(10):1044-1052.
doi: 10.1136/jnnp-2020-325932. Epub 2021 Apr 26.

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies

Simona Balestrini  1   2 , Daniela Chiarello  3   4 , Maria Gogou  3   4 , Katri Silvennoinen  1 , Clinda Puvirajasinghe  4 , Wendy D Jones  1   3   4 , Philipp Reif  5   6   7 , Karl Martin Klein  5   6   7   8 , Felix Rosenow  5   6   7 , Yvonne G Weber  9   10 , Holger Lerche  5   9 , Susanne Schubert-Bast  5 , Ingo Borggraefe  11 , Antonietta Coppola  12 , Serena Troisi  12 , Rikke S Møller  13 , Antonella Riva  14 , Pasquale Striano  14   15 , Federico Zara  14   15 , Cheryl Hemingway  4 , Carla Marini  2   16 , Anna Rosati  2 , Davide Mei  2 , Martino Montomoli  2 , Renzo Guerrini  2 , J Helen Cross  3   4 , Sanjay M Sisodiya  17
Affiliations
Observational Study

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies

Simona Balestrini et al. J Neurol Neurosurg Psychiatry. 2021 Oct.

Abstract

Objective: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.

Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.

Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).

Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.

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Conflict of interest statement

Competing interests: PS has received speaker fees and participated at advisory boards for Biomarin, Zogenyx, GW Pharmaceuticals, and has received research funding from ENECTA BV, GW Pharmaceuticals, Kolfarma srl., and Eisai.

Figures

Figure 1
Figure 1
Algorithm illustrating clinical management and outcome following the discovery of genetic aetiology.
See this image and copyright information in PMC

Comment in

References

    1. Sykiotis GP, Kalliolias GD, Papavassiliou AG. Pharmacogenetic principles in the Hippocratic writings. J Clin Pharmacol 2005;45:1218–20. 10.1177/0091270005281091 - DOI - PubMed
    1. National Research Council (US) Committee on a Framework for Development of a New Taxonomy of Disease . Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington: National Academies Press, 2011. ISBN: 978-0-309-22222-8. - PubMed
    1. Ginsburg GS, Willard HF. Genomic and personalized medicine: foundations and applications. Transl Res 2009;154:277–87. 10.1016/j.trsl.2009.09.005 - DOI - PubMed
    1. Balestrini S, Sisodiya SM. Treatment of epileptic encephalopathies. Curr Pharm Des 2017;23:5667–90. 10.2174/1381612823666170809115827 - DOI - PubMed
    1. Balestrini S, Sisodiya SM. Pharmacogenomics in epilepsy. Neurosci Lett 2018;667:27–39. 10.1016/j.neulet.2017.01.014 - DOI - PMC - PubMed

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