Epilepsja jako zaburzenie wieloskalowej sieci mózgowej: integracja precyzyjnych terapii i nowych platform badawczych
PubMed➕ 27.08.2026Pharmaceutics
Epilepsy as a Multiscale Network Disorder: Integrating Precision Therapeutics and Emerging Experimental Platforms
W skrócie
Epilepsja to poważne schorzenie neurologiczne, w którym u około jednej trzeciej pacjentów leki przeciwpadaczkowe nie działają wystarczająco dobrze. Badania pokazują, że epilepsja nie wynika tylko z nadmiernej aktywności neuronów, ale z wielu powiązanych problemów na różnych poziomach - od molekularnych zmian w mózgu, przez zapalenia, aż po zaburzenia naczyń krwionośnych. Nowe metody badawcze, takie jak modele komórkowe pochodzące ze sztucznych komórek macierzystych czy systemy komputerowe, mogą pomóc w lepszym zrozumieniu choroby i opracowaniu bardziej skutecznych leków dostosowanych do konkretnego pacjenta.
Oryginalny abstract (angielski)
: Epilepsy remains a major neurological disorder, with approximately one-third of patients continuing to experience pharmacoresistant seizures despite the availability of numerous antiseizure medications (ASMs). While current therapies primarily target neuronal hyperexcitability through modulation of ion channels and neurotransmitter systems, increasing evidence suggests that epileptogenesis arises from multiscale interactions involving molecular, cellular, circuit, network, neuroinflammatory, and neurovascular mechanisms. Although therapeutic strategies have diversified, this expanded mechanistic understanding has not yet been fully incorporated into therapeutic development and evaluation. This review integrates current knowledge of multiscale epilepsy pathophysiology with recent therapeutic advances and emerging experimental platforms. : This narrative review synthesized literature identified primarily through PubMed and Google Scholar searches through January 2026, supplemented by targeted updates of therapeutic development and regulatory status through July 2026. Particular emphasis was placed on ion channel modulators, synaptic and neuromodulatory therapies, neuroinflammatory interventions, precision genetic approaches, and human-relevant experimental platforms, including induced pluripotent stem cell (iPSC)-derived models, brain organoids, multi-electrode arrays (MEAs), organ-on-a-chip systems, multi-omics technologies, and artificial intelligence (AI)-based analytical frameworks. : Current and emerging therapies target increasingly diverse molecular, circuit, neuromodulatory, and neuroinflammatory mechanisms. However, drug resistance remains multifactorial, and the long-term effects of therapeutic interventions on network remodeling, neuro-glial interactions, and sustained clinical response remain incompletely understood. NAMs provide complementary capabilities for patient-specific disease modeling, functional network phenotyping, neurovascular modeling, and the integration of molecular, electrophysiological, and computational data across biological scales. : Epilepsy is increasingly recognized as a multiscale network disorder rather than solely a condition of neuronal hyperexcitability. The coordinated use of complementary human-relevant platforms may help incorporate multiscale mechanistic insights into therapeutic development and evaluation, narrow persistent translational gaps, and support more predictive and mechanism-informed treatment strategies.
Metadane publikacji
Journal
Pharmaceutics
Data publikacji
07.08.2026
PMID
42654085
DOI
10.3390/pharmaceutics18080969
Autorzy
Chang W, Kwak AS, Han SH, Song DY, Yoo HI, Lee JH
Słowa kluczowe
New Approach Methodologies (NAMs), epilepsy, multiscale network, precision therapeutics