Innovations in Epilepsy Treatment: From New Drugs to Gene Therapy

Epilepsy: Challenges and the Search for New Solutions

Epilepsy remains one of the serious neurological disorders affecting millions of people worldwide. Despite the availability of more than 20 antiseizure medications (ASMs), a significant portion of patients—about 30-40%—face uncontrolled seizures or severe side effects, highlighting the urgent need for new, more effective, and safer treatment methods [2, 3, 4]. Uncontrolled seizures not only impair quality of life but also increase the risk of comorbid conditions and premature death [3]. Modern research aims to develop innovative approaches that could ensure complete freedom from seizures and improve the prognosis for patients.

New Generations of Antiseizure Medications

Over recent decades, the pharmaceutical industry has introduced many new ASMs that offer an improved tolerability profile compared to older-generation drugs, although their efficacy may be comparable [1]. These new medications facilitate the treatment process and allow therapy to be more precisely tailored to the individual needs of the patient and their comorbid conditions [1].

Among the ASMs recently introduced to the market are:

• Ezogabine, perampanel, brivaracetam, everolimus: These drugs belong to a new generation and are actively used in clinical practice, including in neurosurgery [1].
• Cannabidiol (CBD): Highly purified plant-derived cannabidiol (e.g., Epidiolex®/Epidyolex®) has demonstrated efficacy and safety in treating seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis. Studies also demonstrate its potential in the treatment of other forms of developmental and epileptic encephalopathies and complex treatment-resistant epilepsies [5].
• Fenfluramine (FFA): In a recent multicenter retrospective study, fenfluramine demonstrated efficacy and good tolerability in children and adults with Lennox-Gastaut syndrome, Dravet syndrome, and other developmental and epileptic encephalopathies. Many of these patients had previously failed treatment with several other ASMs [8].

In addition to new molecules, innovative drug delivery routes are being developed, such as intranasal and transdermal systems, which can enhance drug efficacy and minimize side effects [4].

Promising Non-Pharmacological and Biological Methods

In addition to pharmacological developments, other more radical approaches to epilepsy treatment are being actively researched, especially for patients with drug-resistant forms:

• Cell therapy: Methods based on the use of stem cells show promising results in animal models and hold potential for clinical application. They aim to restore damaged neural circuits and reduce epileptic activity [2].
• Gene therapy: This approach involves correcting the genetic defects underlying certain forms of epilepsy. Clinical trials of gene therapy are already underway, opening new horizons in treatment [2, 4].
• Molecular-genetic approaches: Research is focused on therapeutic targets such as neuropeptides, neurotrophic factors, and inhibitory neurotransmitters, which play a key role in regulating neuronal excitability [2].
• Optogenetics: This cutting-edge technology allows the control of neuronal activity using light, which can be used for precise suppression of epileptic foci. It is currently in the preclinical research stage [2].

Personalized Approach and Special Patient Groups

Modern epileptology is increasingly moving towards personalized medicine, which involves a comprehensive assessment of each patient and the selection of therapy that best matches their individual characteristics, type of epilepsy, and comorbid conditions [3].

Special attention is paid to specific patient groups:

• Elderly individuals: The incidence of epilepsy among the elderly is steadily increasing, and by 2030, a third of the population in some developed countries will be over 65 years old [7]. This means a significant increase in the number of elderly patients with epilepsy, many of whom will have comorbid conditions [1, 7]. Diagnosing epilepsy in this age group can be difficult and often requires prolonged video-EEG monitoring [7]. Stroke is the most common cause of epilepsy in the elderly [7]. The selection of ASMs for elderly patients requires consideration of their general health status, drug interactions, and potential side effects [1, 7].
• Pregnant women, patients with HIV infection, tumors, and other groups also require specific therapeutic approaches and careful drug selection [1].

The Future of Epilepsy Treatment: Technology Integration

The future of epilepsy treatment is envisioned in the integration of various innovative technologies. Machine learning, for instance, is already demonstrating potential in improving diagnostics and predicting response to anticonvulsant therapy, helping physicians make more informed decisions [4]. The goal is not just to control seizures, but to achieve their complete absence with minimal side effects, significantly improving the quality of life of patients [2]. The development of precision medicine, taking into account the genetic, molecular, and clinical features of each case, is a key direction for overcoming the challenges associated with drug-resistant forms of epilepsy [3].

Sources

1. New treatment and new drugs in epilepsy therapy. (Current pharmaceutical design, 2017) https://pubmed.ncbi.nlm.nih.gov/29076416/
2. Novel approaches to the treatment of epilepsy. (Epilepsia, 2013) https://pubmed.ncbi.nlm.nih.gov/23106744/
3. New trends and most promising therapeutic strategies for the treatment of epilepsy. (Frontiers in neurology, 2021) https://pubmed.ncbi.nlm.nih.gov/34950099/
4. Innovations in epilepsy treatment: pharmacological strategies and the application of machine learning. (Neurologia i neurochirurgia polska, 2025) https://pubmed.ncbi.nlm.nih.gov/40145575/
5. Systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: seizure frequency changes and adverse events. (Epilepsy research, 2026) https://pubmed.ncbi.nlm.nih.gov/41558068/
6. Diagnostics and management recommendations for infantile epileptic spasm syndrome worldwide: a review and comparative study of international approaches. (Epilepsia, 2026) https://pubmed.ncbi.nlm.nih.gov/42274306/
7. Epilepsy in the elderly: facts and challenges. (Acta neurologica Scandinavica, 2011) https://pubmed.ncbi.nlm.nih.gov/21143593/
8. Efficacy and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: a multicenter, retrospective real-world study. (Epilepsia, 2026) https://pubmed.ncbi.nlm.nih.gov/42334048/

The information in this article is for reference purposes only and does not constitute a guide to self-treatment. Before starting any treatment or changing current therapy, you must consult a qualified physician.