Prevention of Post-MI Heart Failure with Immunomodulatory Therapy

Principal Investigator Program DirectorLastFirstMiddleChenRidong AbstractIncidence and mortality from post myocardial infarctionMIheart failureHFare increasing and becoming a major health problem worldwideThere is an urgent need for novel therapy to minimize MI and promote postMI wound healingAcutelyinterleukinILprotects the myocardium against both ischemic and reperfusion injuryIRIvia interaction of its opioid binding domain with peripheraland oropioid receptors in adult cardiomyocytesChronicallyadministration of low dose rILpromotes cardiac wound healing through activation of high affinity receptor preferably inducing expansion of regulatory T cellsTregsIn additiontreatment with lowdose rILhalts the progression of atherosclerosis and stabilizes established atherosclerotic lesions in animal modelsImportantlyMI and HF patients have a deficiency in Tregs frequency and functionRecent clinical trials demonstrate that low dose rILtherapy was well toleratedpreferentially enhanced Tregsand improved clinical outcomes in patients with autoimmune or inflammatory diseases without causing immunosuppressionThustreatment with rILbased therapy carries a high therapeutic potential to minimize infarct sizeprevent HF development and recurrent MIand improve clinical outcomeHowevercurrent low dose rILtherapy has a very short half life and causes local reaction at injection siteswith an unwanted increase in several innate immune cell types such as natural killer cells and eosinophilsTo obtain ideal outcomes in patientswe have designed a proprietary ILanalog that activates peripheraland oropioid receptors and enables selective stimulation of Tregswhile minimizing negative clinical effectsThe specific aim of this Phase I SBIR proposal is to determineusing a murine model of HF induced withmin closed chest IRIwhether acute or weekly treatment with a proprietary ILanalog will effectively attenuate MI and prevent HF development fordays of follow upAPT ConfidentialPrincipal Investigator Program DirectorLastFirstMiddleChenRidong NarrativeThe innovative approach involves the treatment with an novel ILanalog to activate peripheral opioid receptors and restore regulatory Tcell frequency and function in heart attack patients to minimize heart damage and prevent heart failureAPT Confidential