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RAGE Inhibition Reduces Surgery-Induced Cerebral Edema After Glioma Resection.
Mojtaba Dayyani1, Aleksandr Filippov1, Ian Zhang1
1Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, California, USA.
Neurosurgery
|March 19, 2026
Summary
Novel RAGE inhibitors, TTP488 and FPS-ZM1, effectively reduced cerebral edema after glioma resection in mice, comparable to dexamethasone but without hindering immunotherapy. These RAGE inhibitors represent a promising steroid-sparing approach for brain tumor patients.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Cerebral edema (CE) is a significant cause of neurological decline post-brain tumor resection.
- Corticosteroids manage perioperative CE but have side effects and can impede immunotherapy.
- Targeting the receptor for advanced glycation end products (RAGE) is a potential alternative strategy.
Purpose of the Study:
- To evaluate the efficacy of two RAGE inhibitors, TTP488 and FPS-ZM1, in reducing post-glioma resection CE in murine models.
- To compare the effects of RAGE inhibitors with dexamethasone on CE, neurological function, wound healing, and immunotherapy response.
Main Methods:
- Mice with orthotopic gliomas underwent microsurgical resection and received perioperative TTP488, FPS-ZM1, dexamethasone, or vehicle.
- Postoperative CE was monitored via serial MRI and quantified.
- Neurological function, wound healing, and anti-PD-1 immunotherapy response were assessed; RNA sequencing analyzed gene expression changes.
Main Results:
- Both TTP488 and FPS-ZM1 significantly reduced postoperative CE on day 1 compared to vehicle.
- RAGE inhibitors did not impair anti-PD-1 immunotherapy efficacy, unlike dexamethasone.
- FPS-ZM1 treatment improved neurological recovery, wound healing, and enhanced immunotherapy at higher doses.
Conclusions:
- RAGE inhibitors effectively reduce postoperative CE, comparable to dexamethasone.
- These inhibitors offer a steroid-sparing alternative, preserving immunotherapy efficacy and promoting wound healing.
- RAGE inhibition presents a promising strategy for managing CE in brain tumor patients undergoing immunotherapy.
