University of Pittsburgh and University of Colorado Boulder researchers have developed regulatory T cell therapy to treat reperfusion injury following myocardial infarction (MI, i.e., heart attack). The key treatment for MI is to rapidly re-establish blood flow (reperfusion) to the heart muscle to minimize injury to the heart. This process can lead to dysregulated inflammatory responses called reperfusion injury which can damage tissue previously unharmed by the MI and lead to heart disease. This novel approach aims to regulate the immune response following reperfusion by harnessing the body’s own endogenous regulatory T cells, a cell type responsible for suppressing inflammation and promoting repair. This accomplished through the controlled release of CCL22 protein from biodegradable microparticles (MPs) that are suspended within an injectable hydrogel.
Description
Each year over 800,000 Americans have a heart attack, when part of the heart muscle does not get enough blood. This can lead to permanent heart damage from cardiac cell necrosis. Treatments of the initial MI is routine, but there remains an unmet clinical need to limit inflammatory responses post reperfusion, preventing damage to healthy tissue, promoting repair, and preventing the development of heart disease or death which can affecte 40% of Americans within five years of experiencing an MI.
Applications
• Reperfusion injury
• Heart failure prevention
Advantages
Rapid treatment including fibrinolytics and percutaneous coronary intervention can restore blood flow to the heart and reduce initial tissue damage following a heart attack. Following restoration of blood flow reperfusion injury can occur as immune effector cells see inflammatory damage markers released during the MI. Resulting damage to healthy surrounding heart tissue that had been unaffected by the MI exacerbates the severity of the MI and increases the risk of the patient developing heart failure. Current treatments of MI do not address this risk and it remains an unmet need.
This novel approach uses MPs and injectable hydrogel technology to attract or induce the body’s own Treg to the site of the MI. These degradable polymer MPs contain the CCL22 protein, known to target Treg and the hydrogel (iHEART) suspends the MPs allowing for direct injection and increased retention in the heart muscle.
Invention Readiness
MPs have been developed to release CCL22 in a controlled manner over 70 days. Combining these MPs with a hydrogel system has been shown to enhance MP retention in healthy animal heart tissue. Small scale in vivo studies in a model of ischemia-reperfusion MI have found this novel approach can reduce cardiac damage and improve heart function. Work is required to examine long term benefits of this approach, including in more severe ischemia.
IP Status
Patent pending
