Glioblastomas are an aggressive form of primary tumors that arise in the central nervous system. Glioblastomas are resistant to current modalities of treatment (i.e. surgery, chemotherapy, and radiation therapy) and have one of the worst 5-year survival rates. One challenge in treating glioblastomas is delivering anticancer agents to the brain, which is protected by the blood-brain barrier that rebuffs many molecules from entering the central nervous system.
To address this challenge, scientists at the Massachusetts General Hospital harnessed olfactory ensheathing cells (OECs) to carry molecules undetected from the nasal cavity into the nervous system. These OECs serve as a “Trojan Horse” to bypass the blood-brain barrier in order to treat neurological disorders.
Olfactory ensheathing cells, a type of glial cell, surround and assist olfactory neurons that stretch from the nasal cavity into the olfactory bulb. These olfactory neurons have a rare ability in the nervous system to regenerate when damaged. OECs assist regenerating neurons and can also hone in on damaged and dead cells to be eliminated by phagocytosis. The functions of OECs allow them to travel naturally from the peripheral nervous system to the central nervous system by way of the olfactory neural cells, making these cells a great “Trojan Horse” candidate to bypass the blood-brain barrier.
The authors used OECs to be able to express a fusion protein between yeast cytosine deaminase and uracil phosphoribosyl transferase. The resulting fusion protein could break down the prodrug 5-fluorocytosine (5-FC) into the cytotoxic chemotherapy agent 5-fluorouracil (5-FU) that can kill tumor cells. The OECs were isolated from the mouse olfactory bulb, engineered to express the fusion protein, and injected into mice bearing glioblastoma tumors through intranasal administration. The modified OECs were able to locate and migrate to tumor site in the brain and inhibit growth of the tumors, showing potential for OECs as a “Trojan Horse” to deliver drugs into the brain.
This article titled “Olfactory Ensheathing Cells: A Trojan Horse for Glioma Gene Therapy” was published in Journal of the National Cancer Institute