Novel Therapeutic Targets for Drug-Resistant Epilepsy

Strategic Insights -

Research at Monash University has shed new light on the underlying mechanisms of drug-resistant epilepsy (DRE). By comparing plasma inflammatory biomarkers and monocyte phenotypes in patients with DRE and psychogenic non-epileptic seizures (PNES), researchers identified potential therapeutic targets for the development of new treatments. The study, published in Scientific Reports, found that patients with DRE had a more "proinflammatory" circulating innate immune state, characterized by differences in monocyte phenotype and function.

Key Takeaways:

  • The study assessed plasma inflammatory biomarker concentrations and monocyte phenotype and function in 21 patients with DRE and 19 patients with PNES.
  • No difference in cytokine and chitinase 3-like 1 (CHI3L1) concentrations was seen between the two groups.
  • Patients with DRE had a higher percentage of "classical" monocytes and less "non-classical" monocytes compared to PNES patients.
  • The percentage of "classical" monocytes expressing P2X7R was increased in DRE patients compared to PNES patients.
  • CD11b median fluorescence intensity (MFI) ratio was increased in "classical" and "intermediate" monocytes in DRE patients.
  • P2X7R pore function was similar between the two groups.
  • The study's findings suggest that monocytes may be a novel therapeutic target for DRE.

Statistics:

  • 21 patients with DRE were included in the study.
  • 19 patients with PNES were included in the study.
  • 22 patients with DRE underwent flow cytometry to quantify monocyte phenotype and function.
  • 11 patients with PNES underwent flow cytometry to quantify monocyte phenotype and function.
  • Cytokine levels were similar between the two groups, but differences in monocyte phenotype between the two groups indicate a more "proinflammatory" circulating innate immune state in DRE.

Sources:

  • Huey-Lin Tan, T., Sequeira, R. P., Perucca, P., Kwan, P., O'Brien, T. J., Monif, M. Peripheral cytokine and monocyte phenotype associations in drug-resistant epilepsy. Scientific Reports, 2025, 15(1):1-14. (doi: 10.1038/s41598-025-14402-4).
  • Monash University. Research on Epilepsy Detailed by Researchers at Monash University (Peripheral cytokine and monocyte phenotype associations in drug-resistant epilepsy). Health & Medicine Week, 2025; p 5544.