HBI-002 to Treat Traumatic Injury

Project Summary There is an urgent need for the development of new approaches to treat patients suffering from traumatic injurywhich is the most common cause of death for individuals below ageand a leading cause of death in all age groups in the USEspecially important is the search for therapeutics to address the inflammatorymetabolic and cellular injury mechanisms that result from a traumatic injury and the ensuing ischemia reperfusion injuryIRIExtensive preliminary results and literature reports in models of traumatic injury clearly demonstrate that carbon monoxideCOis cytoprotective and can limit tissue injury and organ dysfunction and reduce mortalityThe pharmacology of CO administration is understood well enough that the examination of CO s therapeutic potential for various applications is very much warranted and neededTo dateCO gas has been the modality of choice in the majority of animal studiesHoweverinhaled CO is not expected to be a pharmaceutically acceptable and viable option for the majority of potential clinical applicationsThe objective of the proposed project is to investigate a novel modality by which to administer CO as a therapeutic agent for the treatment of trauma patients using rectal and oral formulations of COHBIThe safety and tolerability of inhaled CO has been demonstrated in successful Phaseclinical studies supported by well defined preclinical data sets that led to approval by the FDA for human testingThe administration of a defined dose of CO delivered by rectal or oral administration of HBIobviates the problems associated with inhaled or carrier metal bound CO releasing moleculesincluding environmental safety and dosinginhaled COand carrier molecule toxicity and CO release characteristicscarrier metal bound COHBIcomprises rectal and oral formulations containing precise amounts of CO that are easily absorbed from the gastrointestinal tractPreliminary preclinical in vivo pharmacokinetic and pharmacodynamic studies demonstrated proof of concept feasibilitytolerabilityand bioavailabilityThe next step in development is to demonstrate that HBIis effective in limiting inflammation and improving outcomes in animal models as has been shown with CO gas and other forms of CO delivery and to better understand the potential mechanism sof the protectionBased upon these accepted paradigmsour central hypothesis that will be tested in this project isHBIprevents inflammation and end organ failure after hemorrhagic shock and trauma Project Narrative This proposal is intended to support research evaluating whether HBIa rectal and oral carbon monoxideCOtherapeuticcan improve outcomes in animal models of traumatic injuryIf successfulthe project will provide proof of concept for further development of HBIin trauma as a promising therapeutic to improve outcomes in this devastating condition