Novel Use of Neural Stem Cells for the Targeted Treatment of Spinal Cord Gliomas
Alexander E. Ropper, MD
The incidence of primary spinal cord tumors has increased in recent decades. While more common in the brain, tumors also occur in the spinal cord. A variety of types are seen such as astrocytomas, glioblastomas, and ependymomas. While surgery can be effective, patients may be left with paralysis or sensory loss due to the sensitivity of the surrounding tissue that must be dissected. Patients with these tumors may die from worsening spinal cord spread or from infections related to their debilitated condition.
Alternative approaches to the treatment of brain gliomas have received significant attention and this project intends to modify one of these approaches for use in the spinal cord. A novel treatment is the use of neural stem cells (NSCs) to track and kill tumor cells. Neural stem cells have a unique ability to seek, follow, and contact tumor cells in the nervous system, even when the stem cells are administered intravenously. This tumor-cell oriented behavior of stem cells is triggered by molecules that are secreted by tumors during their growth.
Previous work by collaborators of Dr. Ropper has demonstrated that neural stem cells can be genetically engineered to carry a chemical to tumors. Dr. Ropper’s team intends to insert cytosine deaminase into neural stem cells. This enzyme converts the non-toxic compound [5-fluorocytosine (5-FC)] into a potent cancer chemotherapy, (5-fluorouracil, or 5-FU). By utilizing the inherent migratory nature of NSCs to target tumor cells throughout the spinal cord, the team hopes to selectively deliver the toxic chemotherapy only to the tumor, sparing normal spinal cord tissue.
To test this hypothesis, the team will first develop a unique animal tumor model by injecting glioma cells into the spinal cord of rats. Then they will give intravenous or intraspinal genetically engineered stem cells, followed by intravenous injection of the non-toxic precursor containing 5-FC. The team expects the toxic 5-FU chemotherapy compound to be produced only in the immediate vicinity of tumor cells. This would constitute the first multidisciplinary approach to tackle the disease of spinal cord malignant tumors and lead to a better overall prognosis in patients with aggressive malignancies in the spinal cord.