Infant NeuroLUX: A Novel Non-invasive Therapeutic Device for Neonatal Hypoxic Brain Injury

Neonatal hypoxia ischemia is a known cause of cerebral damage resulting from inadequate blood flow and or oxygen delivery to the infant brain beforeduringor after birthThe occurrence among hospital deliveries isperfull term births with a drastic increase among premature newbornsThe deficit in oxygen delivery to the brain results in extensive damage and severe disabilitiesRestoration of blood flow critical for salvage of ischemic tissuehoweveralso causes significant cerebral damage due in part to cytotoxic reactive oxygen speciesROSgenerated upon reintroduction of oxygenThe current standard treatment for neonatal hypoxia ischemia is therapeutic hypothermia applied on averagehours after restoration of blood flow oxygen deliveryA safe and effective neuroprotective intervention that specifically targets reperfusion injury during the early phase of reoxygenation would fill a critical unmet need in the treatment of infants exposed to hypoxia ischemiaOur molecular studies on mitochondrial function uncovered a novel method to prevent ROS generation during early reoxygenationIndeedour studies havefor the first timeiidentified two wavelengths of infrared lightIRLthat specifically and reversibly reduce mitochondrial respiration by acting on cytochrome c oxidaseandiidocumented that IRLapplied at the time of reoxygenationis neuroprotective and limits ROS generationBased on these datawe propose develop iNeuroLUXa device that will safely deliver therapeutic IRL to the infant brainTo achieve this goalPhase I will proposeexperimental aimsConduct ex vivo molecular investigation to define the safe therapeutic IRL dose that can be applied in ourlarge animal studiesAimEstablish the effect of IRL on HIE in a large animal model of neonatal hypoxia ischemiaAimWe willdetermine the effects of IRL on neurologic damage in a neonate swine model of hypoxia ischemia andinvestigate safety of IRL in undamaged tissuesPhase II will build upon the findings in the first phase andDesign and construct a iNeuroLUX light delivery prototype for testing IRL therapyAimEstablish the efficacy of iNeuroLUX and evaluate the concept of iNeuroLUX combination therapy withhypothermiaAimDocument critical safety parameters of iNeuroLUX to move forward with FDA approvalAimThis proposal combines multi disciplinary expertisecompelling preliminary dataand state of the art resources available to our research team to address a highly significant health problem Delivery of newborns is sometimes accompanied by complications that cause a reduction in blood flow or oxygen delivery to their brainresulting in brain damage and disorders such as epilepsy and cerebral palsyRestoration of oxygen back to the brain also worsens brain damage by generating highly toxic agents called free radicalsWe have discovered that treatment with specific wavelengths of infrared lightapplied non invasively at the time when blood flow is restored to the brainsubstantially reduces the production of free radicals and brain damageand we propose to develop this therapy for a clinical treatment for newborns