Zaburzenia kanałów potasowych a medycyna spersonalizowana w epilepsji: Przegląd systematyczny indywidualnych strategii leczenia
Potassium Channelopathies and Precision Medicine Approaches in Epilepsy: A Systematic Review of Personalized Treatment Strategies
W skrócie
Badacze przeanalizowali ponad 2200 publikacji naukowych, aby znaleźć najlepsze sposoby leczenia epilepsji spowodowanej wadami genetycznymi kanałów potasowych w mózgu. Dla każdego typu wady znaleźli różne leki, które mogą działać - na przykład dla niektórych pacjentów skuteczne są chinidyna, kannabidiol czy fluoksetyna, a dla innych mogą pomóc zupełnie inne leki takie jak ezogabina czy 4-aminopirydyna. Przegląd pokazuje, że wybór leku powinien być dostosowany do konkretnej mutacji genetycznej pacjenta, ale wymaga więcej badań, aby potwierdzić skuteczność tych terapii.
Oryginalny abstract (angielski)
OBJECTIVE: This systematic review aimed to summarize recent progress in precision medicine for all studied potassium gene variants related to epilepsy. It analyzed studies conducted in cell and animal models and in humans. METHODS: A comprehensive search was conducted on PubMed, Embase, and Cochrane databases for all years up to 2025. RESULTS: Approximately 2257 papers were reviewed, but only 60 met the inclusion criteria: KCNT1 [n = 38], KCNQ2 [n = 10], KCNQ5 [n = 1], KCNB1 [n = 1], KCNA2 [n = 3], KCNA1 [n = 2], KCNA3 [n = 1], KCNT2 [n = 2], and KCNC1 [n = 2]. Therapies that appear effective for some patients with KCNT1 variants include quinidine, cannabidiol, fluoxetine, and carvedilol. Potential treatments supported by cell and/or animal models include bepridil and antisense oligonucleotide therapy. There is currently no precision therapy for KCNT2 variants; however, potential treatments supported by cell model evidence include quinidine, fluoxetine, loxapine, and riluzole. Emerging potential therapies for KCNQ2-related epilepsy include ezogabine, gabapentin, retigabine, donepezil, amitriptyline, linopirdine, pynegabine, SF0034, and XEN1101. Retigabine and gabapentin are potential therapies for KCNQ5 variants. Cannabidiol is a potential therapy for KCNB1 variants. 4-Aminopyridine is useful for KCNA1 and KCNA2 variants. Gapmer antisense oligonucleotides are a potential treatment for KCNA2 variants. Fluoxetine is a potential therapy for KCNA3 variants. Fluoxetine and compound RE01 are the potential therapies for KCNC1 variants. CONCLUSION: These studies collectively offer valuable insights into precision medicines for genetic epilepsy caused by pathogenic potassium variants. This review is essential because it informs clinical decision-making, including the selection of antiepileptic drugs, thereby supporting its integration into routine clinical care for this population. However, the low level of evidence and the heterogeneity of data from the included studies limit the review.