Preclinical Investigation of Resveratrol and CAR-Macrophage Synergy for IDH1-Mutant Glioblastoma: An AI-Driven, Multi-Scale Modelling Rationale and Protocol

Angus McNab

No eyaf2_v1, OSF Preprints from Center for Open Science

Abstract: Glioblastoma (GBM) remains a clinical death trap with limited progress in decades and dismal survival rates. In this study, we present a computationally optimized, first-in-class therapeutic strategy combining Resveratrol and CAR-macrophages for IDH1-mutant GBM. Using an AI-driven, multi-scale modeling framework integrating ODEs, agent-based modeling, and reaction-diffusion dynamics, we simulated over 740 compute hours and 250 experimental conditions. The optimized combination achieved a predicted 93% tumor volume reduction in silico (95% CI: 90–96%, p < 0.001), far exceeding benchmarks for monotherapies or temozolomide (~30%). Synergy was driven by Resveratrol-induced metabolic reprogramming, antigen upregulation (+33% IL13Rα2/EGFR), and enhanced CAR-macrophage persistence and cytotoxicity (M1/M2 ratio 5.8:1). Monte Carlo sensitivity analysis (n=250) confirmed robustness across parameter ranges, with a peak synergy index of 2.35. This study provides a mechanistically grounded, computationally validated hypothesis for a novel, testable GBM therapy, and lays the foundation for in vitro and in vivo validation. Key model logic, simulation parameters, and setup conditions will be released upon publication to support community replication and refinement.

Date: 2025-04-12
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://osf.io/download/67fbfd6ff90af0bb18763b20/

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:osf:osfxxx:eyaf2_v1

DOI: 10.31219/osf.io/eyaf2_v1

Access Statistics for this paper

More papers in OSF Preprints from Center for Open Science
Bibliographic data for series maintained by OSF ().