Preservation of Spinal Cord Tissue Resulting from Spinal Cord Injury Ischemia: Testing of a Novel Oxygen Release Therapeutic
Abstract
Cervical spinal cord injury (C-SCI) has been a major component of SCI with lingering quality of life due to eroding disabilities with locomotion (gait) and increased muscle tone (spasticity) along with other infirmities that produce a substantial health care responsibility. There are rapidly growing concerns that injury-induced ischemia (e.g., caused by the stretch and avulses post-capillary venules as well as sulcal arterioles, resulting in hemorrhage, reduced spinal cord vascular perfusion, vasospasm, and hypoperfusion) is a significant risk factor for lingering SCI-disabilities. Accordingly, there is an urgent need to test the safety and efficacy of therapeutic measures that target the ischemic zone by utilizing a novel experimental O2 therapeutic (e.g., NanO2), which has excellent potential for rapid translation. When the spinal cord is stretched, contused, partially severed, or compressed by bleeding, loss of nerve function distal to the injury site occurs. Other injuries, including hemorrhage and brain injury often happen. The global incidence is 10.5/100,000 per year. In combat, spinal cord injury accounts for over 11% of casualties. The severity and anatomy of the injury contribute to the outcome, rehabilitation, and complications. Neck injury is the most common and creates the most disability. The worse cases, para/quadriplegia, are permanent, impacting employment or military service. Victims require long-term care with large expenditures from society and reduced quality of life. Secondary infections, decubitus ulcers, muscular contractions, and physiotherapy could be lessened by immediate nerve salvaging therapy. Today, the speed of evacuation to medical care is the best ever. There is no pharmaceutical agent to salvage spinal cord neurons. When injured, the spinal cord blood flow is compromised leading to swelling, decreased oxygen delivery, and extension of injury to cells not killed by the primary event. Cord swelling reduces blood flow causing more neuron death. NanO2 is a perfluorocarbon emulsion comprised of nanoparticles of fluorinated oils that dissolve large quantities of oxygen. They are 1/100-1/1000th the size of red blood cells. Intravenous NanO2 allows areas of decreased blood flow to receive dissolved oxygen when the red cells do not flow. NaO2 is in human stroke trials to deliver needed O2 to prevent acute ischemia while allowing time for clot-busting drugs to be delivered. In traumatic brain injury, NanO2 is capable of salvaging brain tissue. In SCI, there is no definitive therapy wherein giving a short-acting drug would allow a patient to get to therapy. The use of NanO2 will primarily salvage neurons that otherwise would die. Our proposed preclinical animal studies will utilize the NanO2 (NuVox, Tucson, Arizona) in dosages being utilized in humans (plus1/2 and about 2x that dose). Our study will use intravenous NanO2 because that is something that a first responder could perform. The studies will be conducted over 3 years in rats to define the best dose and delay from injury to treatment (20 minutes, 1 hour, 2 hours, and 4 hours). This treatment could quickly transition to human phase 2 trials. These studies will have a standard moderate neck SCI (previously well-defined as a model) with a focus on a major outcome variable (gait movement/functional preservation). It is vitally important that therapy should demonstrate an improvement in nerve-muscle function. Markers of anatomic injury will be assessed with magnetic resonance imaging (MRI) and by microscope inspection of the spinal cord at the end of the experimentation. Certain biomarkers will be assessed to discern the treatment effect. The applicability of this research is to create an intravenous fluid that could be given to a victim within the first few minutes of his/her injury. For the military, this would mean that a combat medic or first echelon hospital could give NanO2. Furthermore, these studies wi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310562
Entities
People
- Prodip Bose
Organizations
- United States Army
- University of Florida