Intramedullary Spinal Tumor Model and Treatment
Abstract
Spinal tumors comprise about 15% of all central nervous system (CNS) tumors. Based on their location, they can be classified into three groups: extradural, intradural-extramedullary, and intramedullary spinal tumors. Among them, intramedullary spinal tumors (IMSTs) are the least common type, which represent 2% to 5% of spinal tumors and arise from the spinal cord itself, leading to invasion and destruction of the gray and white matter. Currently, magnetic resonance imaging allows for characterizing spinal cord tumors, and surgical resection is the most common treatment method. Like brain tumors, the resection and neurologic conditions are greatly dependent on the tumor status in the spinal cord, especially for the infiltrative nonencapsulated tumors, as aggressive resection can lead to significant irreversible neurologic deficits. Radiotherapy and chemotherapy are often reserved for the recurrence of spinal cord tumors or high-grade lesions that are difficult to resect. However, systematic chemotherapy and radiotherapy can lead to the devastating complication of myelopathy. The latest 2021 World Health Organization (WHO) classification for CNS tumors demonstrates the remarkable progress made in characterizing the genetic and molecular landscape of gliomas and ependymomas over the past 5 years. This progress has identified a plethora of potential new drug targets. However, two significant challenges remain that can thwart progress: the inability of most drugs to cross the blood-spinal cord barrier (BSCB) at concentrations sufficient to be effective and the lack of a reliable spinal cord glioma model with high clinical relevance. The BSCB prevents 98% of large molecules from entering the spinal cord and limits entry to essential nutrients. The proposed work aims to create a novel tool capable of reversibly opening the BSCB, thereby delivering effective therapies that would otherwise not enter the spinal cord and will address the Fiscal Year 2022 Rare Cancer Research Program Focus Area of Therapy. We propose to use gold nanoparticles to target the blood vessels and laser excitation to generate mechanical forces capable of transiently opening the BSCB (optoBSCB). As a result, therapeutic anti-cancer drugs can penetrate the compromised BSCB. We specifically aim to (1) engineer highly efficient vascular targeting nanoparticles and optimize optoBSCB, (2) generate a reliable IMST model, and (3) determine the therapeutic benefit of BSCB opening and Taxol delivery using the IMST model. Taxol is among the most widely used oncology drugs but was abandoned for CNS tumor treatment due to poor BBB/BSCB penetration. In particular, we will take advantage of fiberoptics to investigate the light-assisted drug delivery and accumulation to the spinal cord tumor, which is less invasive than other approaches requiring surgery to access the spinal cord. Our ultimate goal is to develop a robust approach to modulate the BSCB to facilitate drug evaluation for IMST treatment and future clinical translation to develop effective targeted therapies for patients with IMST. The development of optoBSCB and the reliable genetically engineered IMST model with high clinical relevance would enable us to better assess the IMST therapy in the preclinical setting within 3 years, which addresses a critical unmet need in drug evaluation for IMST treatment. The success of this work promises to create an entirely new paradigm and new knowledge to investigate drug delivery efficiency to spinal cord tumors and dramatically reduce side effects.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310549
Entities
People
- Zhenpeng Qin
Organizations
- United States Army
- University of Texas at Dallas