Development and Testing of LUCID: A Therapeutic Device for Brain Injury Following Infant Cardiac Arrest

U44 NS125160 - Abstract: Cardiac arrest in infants is a medical emergency requiring rapid resuscitation to restore circulation. However, resuscitation often results in significant brain injury, caused by ischemia/reperfusion injury. Only 36% of infants (<1yr old) treated for out-of-hospital cardiac arrest and 69% of infants that suffer in-hospital cardiac arrest are successfully resuscitated. These infants currently have no therapeutic options to limit brain injury. The current standard treatment for post-cardiac arrest brain injury is therapeutic hypothermia. Unfortunately, recent studies demonstrated that use of therapeutic hypothermia in pediatric cardiac arrest patients does not provide significant benefit beyond what is achieved with controlled normothermia. A safe and effective neuroprotective intervention that specifically targets reperfusion injury would fill a critical unmet need in the treatment of these vulnerable patients. Our molecular studies on mitochondria uncovered a novel method to non-invasively modulate mitochondrial function during reperfusion and reduce brain injury following resuscitation from cardiac arrest. Indeed, our studies have, for the first time: (i) identified two wavelengths of near infrared light (NIR) that specifically and reversibly reduce mitochondrial respiration by acting on cytochrome c oxidase (COX); (ii) documented that NIR, applied at the time of reoxygenation, is neuroprotective in rodent and swine models of infant and pediatric cardiac arrest/resuscitation; and (iii) developed a NIR-delivery system capable of providing therapeutic doses to patients up to 1 year old. Based on these data, we propose to produce the clinical Light Utilizing COX- Inhibitory Device (LUCID), a medical device that will safely deliver therapeutic NIR to the infant brain. To achieve this goal, Phase I will focus on device development and validation of LUCID in 3 experimental aims: • Develop LUCID engineered for clinical use (Aim 1). • Evaluate safety and efficacy of LUCID (Aim 2). • LUCID clinical trial development and HUD and IDE approval (Aim 3). Phase II will utilize the LUCID clinical device and execute the “LUCID Therapy for Infant Cardiac Arrest” (LUTICA) clinical trial (Aim 4). This proposal combines multi-disciplinary expertise, compelling preliminary data, and state-of-the-art resources available to our team to address a significant health problem in a highly vulnerable patient population.