ASTROCYTE-BASED IL-2 GENE THERAPY AS A NOVEL APPROACH TO MODIFY TEMPORAL LOBE EPILEPSY

Temporal lobe epilepsy, the most prevalent form of epilepsy, is often triggered by a traumatic incident such as status epilepticus (SE), which leads to neuroinflammation and gliosis in the hippocampus, preceding spontaneous recurrent seizures. Recently, an AAV-PHP.B-GFAP-interleukin-2 (IL-2) gene therapy exhibited impressive neuroprotective and anti-inflammatory effects in models of traumatic brain injury (TBI) achieved through the expansion of the regulatory T cells (Tregs) population in the brain. (Yshii et al., 2022, Immunology, Vol. 23, No. 6, pp. 878-891) In this study, we investigated whether this IL-2 gene therapy could prevent SE-induced hippocampal damage. For this purpose, we intravenously administered the AAV-PHP.B-GFAP-IL-2 or control vector in C57/BI6 mice, two weeks before intrahippocampal kainic acid injection to induce SE. Behavioural and EEG monitoring revealed no significant differences in SE severity or duration between treatment groups, indicating that IL-2 gene therapy does not alter the initial precipitating insult leading to epilepsy. Hippocampal pathology was assessed three days after SE by performing immunohistochemical staining on brain tissue to obtain a detailed picture of the hippocampal damage. Preliminary results show a significant reduction in Iba1⁺ microglia and GFAP⁺ astrocytes in CA1 and CA3 regions of the hippocampus in IL-2–treated mice, while NeuN⁺ neuronal counts remained unchanged. Ongoing analyses include IL-2 quantification by ProQuantum ELISA and immune profiling by flow cytometry, with early data suggesting increased Tregs among CD4⁺ T cells following IL-2 gene therapy. Further experiments will examine whether IL-2 gene therapy during the latent epileptogenic phase can modify disease progression.