0586759 - FGÚ 2025 RIV US eng J - Journal Article
Danačíková, Šárka - Straka, B. - Daněk, Jan - Kořínek, V. - Otáhal, Jakub
In vitro human cell culture models in a bench-to-bedside approach to epilepsy.
Epilepsia Open. Roč. 9, č. 3 (2024), s. 865-890. E-ISSN 2470-9239
R&D Projects: GA ČR(CZ) GA22-28265S; GA MŠMT(CZ) LX22NPO5107
Institutional support: RVO:67985823
Keywords : drug-resistant epilepsy * genetic testing * in vitro human cell culture * legal and ethical aspects * precision medicine
OECD category: Neurosciences (including psychophysiology
Impact factor: 2.8, year: 2023
Method of publishing: Open access
Result website:
https://doi.org/10.1002/epi4.12941DOI: https://doi.org/10.1002/epi4.12941

Epilepsy is the most common chronic neurological disease, affecting nearly 1%-2% of the world's population. Current pharmacological treatment and regimen adjustments are aimed at controlling seizures, however, they are ineffective in one-third of the patients. Although neuronal hyperexcitability was previously thought to be mainly due to ion channel alterations, current research has revealed other contributing molecular pathways, including processes involved in cellular signaling, energy metabolism, protein synthesis, axon guidance, inflammation, and others. Some forms of drug-resistant epilepsy are caused by genetic defects that constitute potential targets for precision therapy. Although such approaches are increasingly important, they are still in the early stages of development. This review aims to provide a summary of practical aspects of the employment of in vitro human cell culture models in epilepsy diagnosis, treatment, and research. First, we briefly summarize the genetic testing that may result in the detection of candidate pathogenic variants in genes involved in epilepsy pathogenesis. Consequently, we review existing in vitro cell models, including induced pluripotent stem cells and differentiated neuronal cells, providing their specific properties, validity, and employment in research pipelines. We cover two methodological approaches. The first approach involves the utilization of somatic cells directly obtained from individual patients, while the second approach entails the utilization of characterized cell lines. The models are evaluated in terms of their research and clinical benefits, relevance to the in vivo conditions, legal and ethical aspects, time and cost demands, and available published data. Despite the methodological, temporal, and financial demands of the reviewed models they possess high potential to be used as robust systems in routine testing of pathogenicity of detected variants in the near future and provide a solid experimental background for personalized therapy of genetic epilepsies.
Permanent Link: https://hdl.handle.net/11104/0354218