Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Drug-resistant epilepsy — time to target mechanisms

Nature Reviews Neurology volume 16, pages 595–596 (2020)Cite this article

Subjects

Despite the development of many new anti-seizure drugs over the past two decades, around one-third of individuals with epilepsy are without effective treatment. This pharmacoresistance is poorly understood, but new treatments targeting epileptogenesis instead of seizures have shown potential in animal models and are now being translated into the clinic.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Devinsky, O. et al. Epilepsy. Nat. Rev. Dis. Primers 4, 18024 (2018).

    Article  Google Scholar 

  2. Löscher, W., Potschka, H., Sisodiya, S. M. & Vezzani, A. drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol. Rev. 72, 606–638 (2020).

    Article  Google Scholar 

  3. Chen, Z., Brodie, M. J., Liew, D. & Kwan, P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs. JAMA Neurol. 75, 279 (2018).

    Article  Google Scholar 

  4. Lerche, H. et al. Ion channels in genetic and acquired forms of epilepsy. J. Physiol. 591, 753–764 (2013).

    Article  CAS  Google Scholar 

  5. Doeser, A. et al. Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug. Brain 138, 371–387 (2015).

    Article  Google Scholar 

  6. Tang, M., Park, S. H., De Vivo, D. C. & Monani, U. R. Therapeutic strategies for glucose transporter 1 deficiency syndrome. Ann. Clin. Transl Neurol. 6, 1923–1932 (2019).

    Article  CAS  Google Scholar 

  7. Wolff, M. et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain 140, 1316–1336 (2017).

    Article  Google Scholar 

  8. French, J. A. et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST‑3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 388, 2153–2163 (2016).

    Article  CAS  Google Scholar 

  9. Wykes, R. C. et al. Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy. Sci. Transl Med. 4, 161ra152 (2012).

    Article  Google Scholar 

  10. Han, Z. et al. Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome. Sci. Transl Med. 12, eaaz6100 (2020).

    Article  Google Scholar 

Download references

Acknowledgements

The work of H.L. is supported by the German Research Foundation (DFG, Research Unit FOR-2715, grants Le 1030/14-1, /15-1 and /16-1) and by the Federal Ministry for Education and Research (BMBF, Treat-ION, 01GM1907A).

Author information

Authors and Affiliations

  1. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    Holger Lerche

Authors
  1. Holger Lerche
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Holger Lerche.

Ethics declarations

Competing interests

H.L. has received personal honoraria for consulting or speaking from Arvelle, Bial, Biomarin, Desitin, Eisai and UCB; travel support from Bial, Desitin, Eisai and UCB; and research support from Bial, none directly related to any of the work presented here. He is a clinical investigator of the eslicarbazepine acetate trial (EudraCT Number: 2018-002747-29).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lerche, H. Drug-resistant epilepsy — time to target mechanisms. Nat Rev Neurol 16, 595–596 (2020). https://doi.org/10.1038/s41582-020-00419-y

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41582-020-00419-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing