GLUTAMINASE, METHODS AND USES THEREOF
WO2025057133
The present disclosure relates to a glutaminase for use in the treatment of a condition susceptible of being improved or prevented by a decrease of systemic glutamine bioavailability, in particular for use in the treatment of a glioma. The present disclosure also describes a pharmaceutical composition comprising a glutaminase, preferably a human-recombinant glutaminase (GLS1).
- No BBB Penetration Required – Effectively starves tumors without the need to cross the blood-brain barrier; - Selective Tumor Targeting – Exploits a metabolic vulnerability unique to GBM cells; - Minimal Systemic Toxicity – GLS1 therapy is well-tolerated, sparing healthy cells while disrupting tumor metabolism; - Broad Oncology Potential – Can be applied to other glutamine-dependent cancers, such as lung, pancreatic, and colorectal cancer. Current GBM therapies face limited efficacy, significant side effects, and high relapse rates due to BBB restrictions and tumor metabolic adaptability. Our systemic GLS1 therapy provides multiple advantages over existing solutions: - Enhanced Survival Potential – Directly disrupts GBM’s metabolic reliance on glutamine, potentially prolonging patient survival; - Targeted Metabolic Intervention – Unlike intracellular glutaminase inhibitors or glutamine transport blockers, our therapy bypasses the BBB and systemically eliminates glutamine availability, depriving tumors of a key nutrient; - Minimized Toxicity – Healthy cells are spared, avoiding severe side effects observed in previous systemic approaches like glutaminase-asparaginase hybrids, which failed due to toxicity; - Novel systemic metabolic approach – Unlike existing metabolic therapies, which attempt to inhibit intracellular pathways, GLS1 therapy eliminates glutamine at its source, making it a first-in-class metabolic disruption approach for GBM.



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