The field of gene therapy for malignant glioma has made important advances since the first gene transfer studies were performed 20 years ago. Multiple Phase I/II trials and two Phase III trials have been performed and have demonstrated the feasibility and safety of intratumoral vector delivery in the brain. Sitimagene ceradenovec is an adenoviral vector encoding the herpes simplex thymidine kinase gene, developed by Ark Therapeutics Group plc (UK and Finland) for the treatment of patients with operable high-grade glioma. In preclinical and Phase I/II clinical studies, sitimagene ceradenovec exhibited a significant increase in survival. Although the preliminary results of a Phase III clinical study demonstrated a significant positive effect of sitimagene ceradenovec treatment on time to reintervention or death when compared with standard care treatment (hazard ratio: 1.43; 95% CI: 1.06-1.93; p < 0.05), the European Committee for Medicinal Products for Human Use did not consider the data to provide sufficient evidence of clinical benefit. Further clinical evaluation, powered to demonstrate a benefit on a robust end point, is required. This article focuses on sitimagene ceradenovec and provides an overview of the developments in the field of gene therapy for malignant glioma.

Background/Objectives: The anterior communicating artery (AcomA) is one of the most common sites of intracranial aneurysms. We aimed to investigate the effect of routine extradural anterior clinoidectomy (EAC) and extradural lamina terminalis fenestration (ELTF) on the incidence of shunt-dependent hydrocephalus (SDH) and gyrus rectus injury in patients undergoing microsurgical clip reconstruction. Methods: This matched case–control study included 15 patients treated with routine EAC/ELTF between July 2023 and June 2025, matched 1:2 to 30 historical controls (2000–2019) by aneurysm size, location, dome-to-neck ratio, and rupture status. The primary outcome was the incidence of SDH. The secondary outcomes included the incidence of gyrus rectus hypodensity/injury and clinical outcomes, as assessed by the modified Rankin Scale (mRS) at discharge and follow-up. Results: Among 15 cases, 6 had ruptured aneurysms, 4 had unruptured aneurysms, and 5 were recanalized post-endovascular treatment. EAC was performed in all cases; ELTF was performed in 83% of ruptured cases. SDH occurred in 33% of ruptured cases versus 90% in controls (p = 0.02). Gyrus rectus hypodensity occurred in 13% of cases vs. 50% of controls (p = 0.01). EAC/ELTF was associated with reduced odds of SDH (OR: 0.06; 95% CI: 0.004–0.80; p = 0.03) and gyrus rectus hypodensity (OR: 0.15; 95% CI: 0.03–0.80; p = 0.03). A poor outcome (mRS >2) was seen in 27% at discharge, improving to 14% at follow-up (with a median of 11 months). Delayed cerebral ischemia occurred in 33% of ruptured cases. Conclusions: Routine EAC/ELTF may reduce SDH and gyrus rectus injury after AComA aneurysm clip reconstruction, particularly in ruptured cases. Prospective multi-center studies are needed to validate these preliminary findings.