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Intranasal Modified Temozolomide (IM-TMZ) is an investigational formulation of the standard chemotherapy agent temozolomide, specifically designed for direct administration to the brain via the intranasal route. Developed by Center Trials & Treatment Europe, this approach aims to bypass the blood-brain barrier (BBB) by utilizing the olfactory and trigeminal nerve pathways, thereby delivering therapeutic doses directly to the neoplastic process in the central nervous system while potentially reducing systemic toxicity and side effects such as myelosuppression. Temozolomide is a prodrug that undergoes spontaneous hydrolysis at physiological pH to its active metabolite, MTIC, which acts as a DNA alkylating agent. It methylates DNA primarily at the O6 and N7 positions of guanine, leading to DNA damage and subsequent apoptosis in tumor cells. IM-TMZ is currently being evaluated in Phase 1 clinical trials for the treatment of high-grade gliomas, including glioblastoma, gliosarcoma, and Grade 4 astrocytoma.
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