By Ana Espino | Published on February 12, 2026 | 3 min read
Epilepsy is a chronic neurological
disorder characterized by abnormal electrical activity in the brain, leading to
seizures that are often sudden and disabling. While the majority of patients
respond to antiseizure medications, approximately 30% develop drug‑resistant
epilepsy, defined by the failure of at least two appropriately chosen and
well‑tolerated treatments. This refractory form is associated with a major
deterioration in quality of life, an increased risk of psychiatric
comorbidities, and premature mortality, notably due to SUDEP (sudden
unexpected death in epilepsy).
Current management remains largely
symptomatic, focusing on seizure reduction without addressing the
underlying causes of the disease. Treatments remain ineffective in many genetic
or syndromic epilepsies, for which no specific validated therapeutic
approach is currently available. This lack of tailored solutions highlights
the need to move beyond a one‑size‑fits‑all approach to antiseizure
therapy.
In this context, the main
therapeutic challenge lies in the development of individualized strategies
capable of directly targeting the pathogenic mechanisms specific to each type
of epilepsy. Precision medicine therefore emerges as a particularly
promising avenue. This study was initiated to evaluate recent advances in targeted
therapies in epilepsy, by analyzing available preclinical and clinical data
in order to define their potential and limitations within the framework of personalized
care.
Does targeting mean winning ?
The article is based on a structured
narrative review of targeted therapies developed for rare or genetic
epilepsies. The approach combines evidence from animal models, patient‑derived
cellular studies, and available clinical trials. Several specific
syndromes are explored, including pyridoxine‑dependent epilepsy, GLUT1
deficiency syndrome, tuberous sclerosis complex (TSC), and genetic
epileptic encephalopathies related to SCN2A, KCNT1, and GRIN2B.
Some targeted treatments, such as pyridoxine
or the ketogenic diet, demonstrated clinical efficacy early on, well
before the underlying molecular mechanisms were fully understood. Everolimus,
an mTOR pathway inhibitor, achieved significant results in TSC, with response
rates close to 40% in phase III clinical trials. In SCN2A gain‑of‑function
epilepsies, sodium channel blockers have shown clear clinical benefit,
supported by both animal models and documented clinical cases. More
experimental approaches are also discussed, including modulation of the
glutamatergic pathway via GluN2C, as well as targeting neuro‑immune
inflammation through mediators such as IL‑1β and CXCL10, paving the way
for future combination therapies.
However, the inconsistent efficacy
of certain options—such as quinidine in KCNT1‑related epilepsies—highlights
the limitations of translating preclinical findings into clinical practice
and underscores the need for rigorous methodological frameworks to validate
these targeted approaches.
Personalizing epilepsy care: mission possible?
Drug‑resistant epilepsy is a severe
neurological condition, marked by persistent seizure activity despite
standard treatments. The central challenge remains the inability of current
approaches to address underlying disease mechanisms, particularly in
genetic or syndromic forms.
The objective of this study was to review
recent advances in targeted therapies, drawing on preclinical and
clinical evidence obtained in well‑defined subgroups of rare epilepsies. The
findings confirm that precision medicine represents a credible therapeutic
pathway, with demonstrated benefits in conditions such as TSC, GLUT1
deficiency, and SCN2A‑related epilepsies, while also highlighting
the heterogeneity of responses and the complexity of clinical
implementation.
However, limitations remain and
justify further research. Future efforts should include large‑scale multicenter clinical
trials, in‑depth functional characterization of genetic variants,
and the development of standardized protocols for the use of targeted
therapies in neurology. Identifying early therapeutic windows,
integrating drug repurposing strategies, and strengthening collaboration
between clinicians, geneticists, and researchers will be essential to
accelerate the translation of discoveries into truly personalized epilepsy
care.
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
