Non-invasive infrared light therapy and medical device to treat spinal cord injury - Currently, there are no approved interventions that significantly attenuate the acute injury and inflammatory response in the initial early (< 24 h) phase following SCI which leads to neuronal death. Following the initial trauma of spinal cord injury (SCI), a secondary cascade of events characterized by damage to the vasculature of the spinal cord occurs, triggering mitochondrial dysfunction. The main source of ROS (reactive oxygen species; free radicals) production is the mitochondria. During tissue injury, calcium is released which activates mitochondrial proteins. The hyperactivate mitochondria dramatically increase ROS production, which then initiate cellular death cascades causing further damage to the spinal cord and inhibit neuronal regeneration. Thus, there is an urgent need to reduce ROS production and to re-establish mitochondrial homeostasis soon after SCI. A critical challenge, however, in addressing SCI is to devise an intervention that attenuates the acute phase of injury (<24 h) to positively impact long term functional mobility. Pharmaceutical agents are limited because 1) they must be delivered through the bloodstream causing a significant delay for building up efficient concentrations at the target site, 2) act systemically, and 3) must cross several membrane systems (i.e., blood- spinal cord barrier), therefore, resulting in a major delay to establish effective intracellular and more precisely intramitochondrial concentrations to restore mitochondrial homeostasis. To overcome the limitations of drug delivery we have discovered, for the first time, specific wavelengths of infrared light (IRL) that allows us to control a key mitochondrial enzyme, cytochrome c oxidase (COX). Our central hypothesis, supported by strong rodent data, is that application of IRL normalizes mitochondrial hyperactivity in the injured spinal cord, leading to robust neuroprotection. Our IRL technology circumvents the intrinsic barriers of pharmacological approaches because 1) it is noninvasive and safe, 2) can begin prior to surgical decompression and stabilization; 3) instead of scavenging ROS, our technology prevents the generation of ROS by normalizing electron transport chain (ETC) function post injury, 4) it is applied locally at the site of injury and not systemically, 5) does not depend on delivery by blood flow, 6) the effect on COX activity is immediate and fully reversible, 7) it has therapeutic application that can be easily achieved and implemented at the crucial early phase of SCI, and 8) it can seamlessly be translated into the clinic. To test our hypothesis and achieve our objective of developing a therapeutic medical device for treatment of traumatic SCI, we will: Aim 1: Optimize inhibition of the mitochondrial hyperactivity following SCI using our noninvasive infrared light technology in the rat small animal model of contusion SCI; Aim 2: To demonstrate delivery of therapeutic doses of infrared light in live pigs, human cadavers, and computer simulations. Aim 3: To develop the spinal cord targeted human IRL delivery system, SpinaLUX. This novel approach identifies and answers key gaps in spinal cord injury research that will help move the field forward.
