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Gene therapy for epilepsy : An emerging, promising approach for a serious neurological disorder

Ledri, Marco LU and Kokaia, Merab LU (2026) In Journal of Internal Medicine 299(3). p.302-327
Abstract

Gene therapy is emerging as a groundbreaking strategy for treating epilepsy, offering new hope to patients who do not respond to conventional medications. Despite advancements in anti-seizure treatments, nearly 30%–40% of individuals with epilepsy continue to experience uncontrolled seizures, highlighting the urgent need for more effective and long-lasting solutions. By addressing the underlying causes of epilepsy at the genetic level, gene therapy represents a paradigm shift in treatment. Two key approaches are being explored: (1) activating or supplementing beneficial genes to suppress seizures and (2) silencing harmful genes or pathways that contribute to epilepsy. To achieve these objectives, viral vectors, such as adeno-associated... (More)

Gene therapy is emerging as a groundbreaking strategy for treating epilepsy, offering new hope to patients who do not respond to conventional medications. Despite advancements in anti-seizure treatments, nearly 30%–40% of individuals with epilepsy continue to experience uncontrolled seizures, highlighting the urgent need for more effective and long-lasting solutions. By addressing the underlying causes of epilepsy at the genetic level, gene therapy represents a paradigm shift in treatment. Two key approaches are being explored: (1) activating or supplementing beneficial genes to suppress seizures and (2) silencing harmful genes or pathways that contribute to epilepsy. To achieve these objectives, viral vectors, such as adeno-associated viruses and lentiviruses, have shown promise in delivering targeted genetic interventions. In parallel, cutting-edge techniques such as optogenetics, chemogenetics, and clustered regularly interspaced short palindromic repeat-based gene editing are enhancing the precision of these therapies, enabling greater control over neuronal activity. However, significant challenges exist, including ensuring safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects. This review examines recent developments in gene therapy for epilepsy, assessing its potential to deliver targeted, long-lasting treatments for drug-resistant epilepsy. By examining current strategies, therapeutic targets, and emerging technologies, it provides insights into the promising future of gene therapy as a transformative tool in epilepsy treatment and summarizes current clinical trials utilizing gene and cell therapy technologies for epilepsy.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chemogenetics, epilepsy, gene therapy, optogenetics, targeted therapy, viral vectors
in
Journal of Internal Medicine
volume
299
issue
3
pages
26 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:41366856
  • scopus:105024685748
ISSN
0954-6820
DOI
10.1111/joim.70059
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
id
cedb1d94-9bb7-46c7-bec2-0447952fa338
date added to LUP
2026-03-02 15:22:32
date last changed
2026-03-02 15:23:18
@article{cedb1d94-9bb7-46c7-bec2-0447952fa338,
  abstract     = {{<p>Gene therapy is emerging as a groundbreaking strategy for treating epilepsy, offering new hope to patients who do not respond to conventional medications. Despite advancements in anti-seizure treatments, nearly 30%–40% of individuals with epilepsy continue to experience uncontrolled seizures, highlighting the urgent need for more effective and long-lasting solutions. By addressing the underlying causes of epilepsy at the genetic level, gene therapy represents a paradigm shift in treatment. Two key approaches are being explored: (1) activating or supplementing beneficial genes to suppress seizures and (2) silencing harmful genes or pathways that contribute to epilepsy. To achieve these objectives, viral vectors, such as adeno-associated viruses and lentiviruses, have shown promise in delivering targeted genetic interventions. In parallel, cutting-edge techniques such as optogenetics, chemogenetics, and clustered regularly interspaced short palindromic repeat-based gene editing are enhancing the precision of these therapies, enabling greater control over neuronal activity. However, significant challenges exist, including ensuring safe and efficient gene delivery, maintaining long-term therapeutic effects, and mitigating potential side effects. This review examines recent developments in gene therapy for epilepsy, assessing its potential to deliver targeted, long-lasting treatments for drug-resistant epilepsy. By examining current strategies, therapeutic targets, and emerging technologies, it provides insights into the promising future of gene therapy as a transformative tool in epilepsy treatment and summarizes current clinical trials utilizing gene and cell therapy technologies for epilepsy.</p>}},
  author       = {{Ledri, Marco and Kokaia, Merab}},
  issn         = {{0954-6820}},
  keywords     = {{chemogenetics; epilepsy; gene therapy; optogenetics; targeted therapy; viral vectors}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{302--327}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Internal Medicine}},
  title        = {{Gene therapy for epilepsy : An emerging, promising approach for a serious neurological disorder}},
  url          = {{http://dx.doi.org/10.1111/joim.70059}},
  doi          = {{10.1111/joim.70059}},
  volume       = {{299}},
  year         = {{2026}},
}