Title : Intranasal drug delivery: Perillyl Alcohol/NEO100 for glioblastoma leads the way
Abstract:
Malignancies located in the brain are difficult to treat, because most therapeutic agents are unable to enter the brain parenchyma from the circulation, due to the obstacle placed by the blood-brain barrier (BBB). Intranasal delivery of anticancer agents holds potential as a more effective treatment approach, because direct nose-to-brain transport may circumvent the BBB, resulting in greater amount of therapeutic reaching the intracranial lesions. However, no intranasal anticancer agent has reached the market yet. We are studying perillyl alcohol (POH), a naturally occurring monoterpene related to limonene, and its pharmaceutical-grade, highly pure derivative NEO100 (NeOnc Technologies, Inc.), for purposes of intranasal delivery to cancer patients with brain-localized malignancies. In ongoing Phase 1/2 trials with recurrent malignant glioma patients, initial results are pointing to encouraging activity of intranasal POH and NEO100, along with high safety and maintained quality of life. These promising outcomes are supported by mechanistic studies of the molecular function of POH/NEO100, which revealed pleiotropic effects on key intracellular growth-regulatory pathways, including inhibition of Ras oncoprotein function, cell cycle arrest, aggravation of endoplasmic reticulum stress, and potent induction of apoptosis. In all, studies with POH/NEO100 lead the way toward clinical application of intranasal drug delivery as a well-tolerated and effective means to treat malignancies in the brain.
