Editing Epilepsy (section)

==Research directions==
Epilepsy research aims to uncover the causes of seizures, improve diagnosis, and develop more effective treatments. It spans genetics, neuroscience, pharmacology, and biomedical engineering, with the shared goal of reducing the burden of disease. Researchers also study how epilepsy develops ([[epileptogenesis]]), seeking ways to prevent it entirely.

=== Animal models ===
[[Animal models of epilepsy|Animal models]] play a central role in epilepsy research, providing insight into seizure mechanisms, disease progression, and treatment effects. Rodents are most commonly used, with models based on chemical induction (e.g. kainic acid, pilocarpine), electrical stimulation (e.g. [[Kindling model of epilepsy|kindling]]), genetic mutations, and others.<ref>Guillemain, I., Kahane, P. & Depaulis, A. Animal models to study aetiopathology of epilepsy: what are the features to model? Epileptic Disord 14, 217–225 (2012).</ref> Other species, including [[zebrafish]], [[Dog|dogs]], and non-human primates, are also employed to capture features not easily replicated in rodents, such as complex behaviors or chronic seizure patterns. These models help researchers study epileptogenesis, test antiseizure drugs, and explore surgical or neuromodulatory interventions. While no model captures the full complexity of human epilepsy, they remain essential for translational research.<ref>{{Cite journal |last=Grone |first=Brian P |last2=Baraban |first2=Scott C |date=2015 |title=Animal models in epilepsy research: legacies and new directions |url=https://www.nature.com/articles/nn.3934 |journal=Nature Neuroscience |language=en |volume=18 |issue=3 |pages=339–343 |doi=10.1038/nn.3934 |issn=1097-6256}}</ref>

=== Genetics and molecular research ===
Advances in genetics have transformed the understanding of epilepsy, particularly in early-onset and treatment-resistant forms. Mutations in genes affecting ion channels, synaptic transmission, and mTOR signaling pathways have been linked to a growing number of epilepsy syndromes, including Dravet syndrome (SCN1A), PCDH19-related epilepsy, and familial focal epilepsies. High-throughput sequencing has enabled the discovery of de novo mutations in severe developmental and epileptic encephalopathies. In parallel, research into polygenic risk and epigenetic mechanisms is expanding the view of common epilepsies as complex traits. Molecular studies also support the development of targeted therapies, such as precision treatments for specific genetic subtypes.<ref>{{Cite journal |last=Perucca |first=Piero |last2=Perucca |first2=Emilio |date=2019-05-01 |title=Identifying mutations in epilepsy genes: Impact on treatment selection |url=https://www.sciencedirect.com/science/article/abs/pii/S0920121119300270 |journal=Epilepsy Research |volume=152 |pages=18–30 |doi=10.1016/j.eplepsyres.2019.03.001 |issn=0920-1211}}</ref>

=== Epileptogenesis and biomarkers ===
Understanding how epilepsy develops ([[epileptogenesis]]) is a major focus of current research. This includes identifying biomarkers that predict who is at risk of developing epilepsy. EEG patterns, neuroimaging features, and molecular signals in blood or cerebrospinal fluid are being investigated as early indicators. The goal is to detect epilepsy before chronic seizures begin and to develop interventions that prevent or halt this process. While no validated biomarker is yet in clinical use, this area holds promise for future disease-modifying therapies.<ref>{{Cite journal |last=Pitkänen |first=Asla |last2=Engel |first2=Jerome |date=2014-04-01 |title=Past and Present Definitions of Epileptogenesis and Its Biomarkers |url=https://www.sciencedirect.com/science/article/pii/S1878747923008930 |journal=Neurotherapeutics |volume=11 |issue=2 |pages=231–241 |doi=10.1007/s13311-014-0257-2 |issn=1878-7479|pmc=3996117 }}</ref>

=== Antiseizure drug development ===
The development of new antiseizure medications remains a priority, especially for people with drug-resistant epilepsy. Current research focuses on compounds with novel mechanisms of action, better safety profiles, and disease-modifying potential. High-throughput screening, including zebrafish and organoid models, accelerates early-stage discovery, while [[Pharmacogenomics|pharmacogenomic]] studies aim to personalize drug selection. [[Cannabinoid|Cannabinoids]] and [[Neurosteroid|neurosteroids]] are also under investigation for specific syndromes and seizure types.<ref>{{Cite journal |last=Löscher |first=Wolfgang |last2=Klein |first2=Pavel |date=2021 |title=The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8408078/ |journal=CNS drugs |volume=35 |issue=9 |pages=935–963 |doi=10.1007/s40263-021-00827-8 |issn=1179-1934 |pmc=8408078 |pmid=34145528}}</ref><ref>{{Cite journal |last=Rho |first=Jong M |last2=White |first2=H Steve |date=2018 |title=Brief history of anti-seizure drug development |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6293064/ |journal=Epilepsia Open |volume=3 |issue=Suppl Suppl 2 |pages=114–119 |doi=10.1002/epi4.12268 |issn=2470-9239 |pmc=6293064 |pmid=30564769}}</ref>

===Seizure prediction===
The unpredictability of seizures is a major concern for many people with epilepsy, and seizure prediction has been a longstanding focus of research. Early efforts were limited by small datasets and inconsistent results; however, advances in computational modeling, long-term EEG recording, and machine learning have led to renewed interest in the field. Public EEG databases and algorithm competitions have helped standardize evaluation and fostered the development of more accurate methods. In one clinical trial, prospective seizure prediction using [[Electrocorticography|intracranial EEG]] was achieved in a small group of participants. Current approaches often integrate network models of brain activity, multimodal data sources, and closed-loop systems capable of both detecting and responding to pre-ictal changes. These developments have laid the groundwork for future large-scale clinical trials and the potential integration of seizure forecasting into clinical practice.<ref>{{Cite journal |last=Kuhlmann |first=Levin |last2=Lehnertz |first2=Klaus |last3=Richardson |first3=Mark P. |last4=Schelter |first4=Björn |last5=Zaveri |first5=Hitten P. |date=2018 |title=Seizure prediction — ready for a new era |url=https://www.nature.com/articles/s41582-018-0055-2 |journal=Nature Reviews Neurology |language=en |volume=14 |issue=10 |pages=618–630 |doi=10.1038/s41582-018-0055-2 |issn=1759-4766|hdl=2164/11941 |hdl-access=free }}</ref>

=== Mechanistic modeling and alternative pathways ===
Mathematical and [[Computational models in epilepsy|computational models]] are increasingly used to simulate the neural dynamics underlying seizures. Reductionist models such as the Epileptor use ordinary differential equations to replicate interictal and ictal discharges observed in experimental data.<ref>{{Cite journal |last1=Jirsa |first1=Viktor K. |last2=Stacey |first2=William C. |last3=Quilichini |first3=Pascale P. |last4=Ivanov |first4=Anton I. |last5=Bernard |first5=Christophe |date=August 2014 |title=On the nature of seizure dynamics |journal=Brain |language=en |volume=137 |issue=8 |pages=2210–2230 |doi=10.1093/brain/awu133 |issn=1460-2156 |pmc=4107736 |pmid=24919973}}</ref> More detailed versions, including the Epileptor-2, incorporate physiological variables such as ion concentrations and synaptic resource availability.<ref>{{Cite journal |last1=Chizhov |first1=Anton V. |last2=Zefirov |first2=Artyom V. |last3=Amakhin |first3=Dmitry V. |last4=Smirnova |first4=Elena Yu |last5=Zaitsev |first5=Aleksey V. |date=2018-05-31 |title=Minimal model of interictal and ictal discharges "Epileptor-2" |journal=PLOS Computational Biology |language=en |volume=14 |issue=5 |pages=e1006186 |bibcode=2018PLSCB..14E6186C |doi=10.1371/journal.pcbi.1006186 |issn=1553-7358 |pmc=6005638 |pmid=29851959 |doi-access=free}}</ref> These models suggest that fluctuations in extracellular potassium and intracellular sodium levels may play a key role in the emergence and termination of seizures.<ref>{{Cite web |title=Epileptor-2 model |url=https://www.ioffe.ru/CompPhysLab/MyPrograms/Epileptor-2/Epileptor-2.html}}</ref>

===Potential future therapies===
Several novel therapeutic strategies are under investigation for epilepsy. [[Gene therapy for epilepsy|Gene therapy]] is being studied in some types of epilepsy.<ref>{{cite journal | vauthors = Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L | title = Gene therapy in status epilepticus | journal = Epilepsia | volume = 54 | issue = Suppl 6 | pages = 43–45 | date = September 2013 | pmid = 24001071 | doi = 10.1111/epi.12275 | doi-access = free }}</ref> Medications that alter immune function, such as [[intravenous immunoglobulin]]s, may reduce the frequency of seizures when including in normal care as an add-on therapy; however, further research is required to determine whether these medications are very well tolerated in children and in adults with epilepsy.<ref>{{cite journal | vauthors = Panebianco M, Walker L, Marson AG | title = Immunomodulatory interventions for focal epilepsy | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 10 | pages = CD009945 | date = October 2023 | pmid = 37842826 | doi = 10.1002/14651858.CD009945.pub3 | pmc = 10577807 | collaboration = Cochrane Epilepsy Group }}</ref> Noninvasive [[stereotactic radiosurgery]] is, {{as of|2012|lc=y}}, being compared to standard surgery for certain types of epilepsy.<ref>{{cite journal | vauthors = Quigg M, Rolston J, Barbaro NM | title = Radiosurgery for epilepsy: clinical experience and potential antiepileptic mechanisms | journal = Epilepsia | volume = 53 | issue = 1 | pages = 7–15 | date = January 2012 | pmid = 22191545 | pmc = 3519388 | doi = 10.1111/j.1528-1167.2011.03339.x }}</ref>