Epilepsy, a neurological disorder affecting approximately 60 million individuals globally, poses a significant medical challenge with a substantial unmet need. Temporal lobe epilepsy is the most prevalent form, often triggered by traumatic incidents or status epilepticus (SE), resulting in hippocampal damage characterized by neuronal loss, astro- and microgliosis and neuroinflammation preceding the spontaneous recurrent seizures. Recently, an AAV-PHP.B-GFAP-interleukin-2 (IL-2) gene therapy exhibited impressive neuroprotective and anti-inflammatory effects in mouse models of traumatic brain injury (TBI), stroke and MS achieved through the expansion of regulatory T cells (Tregs) in the brain. (Yshii et al., 2022) To assess the efficacy of this viral vector in preventing SE-related damage, such as neuroinflammation and neuronal cell death, we administered the AAV-PHP.B-GFAP-IL-2 or AAV-PHP.B-GFAP-GFP (control) vector in C57BI6 mice, intravenously two weeks before unilateral intrahippocampal kainic acid injection (to induce SE). After three days, the mice were sacrificed and immunohistochemical staining was performed on brain tissue to obtain a detailed picture of the hippocampal damage. Preliminary results demonstrate a decreased trend in Iba+ cells in the hippocampus and a reduction in GFAP+ cells in the CA1 and CA3 regions among mice injected with IL-2 vector, compared to the control group. For neurons (NeuN+ cells) the numbers between the IL-2 group and control group remain relatively consistent. These encouraging outcomes inspire optimism for a follow up experiment in which we will administer the viral vector during the latent period of epileptogenesis aiming at accomplishing clinically significant modifications in disease progression.