Design and Delivery of TAT Fusion Proteins for Cardiopulmonary Resuscitation

Type of Award: Catalyst
Date Awarded: January 2012
Award End Date: December 2013
Amount Awarded: $ 200,000.00
PI(s): Terry Vanden Hoek, MD, UIC; Alan Leff, MD, UChicago;

Abstract: Cardiac arrest is a leading cause of death among women and men in the United States, with a greater public health impact than cancer, HIV, stroke or infectious diseases. Despite this public health challenge, no drugs have been developed for cardiopulmonary resuscitation (CPR) that improve long-term survival after cardiac arrest. Only a few therapies—use of a defibrillator, CPR with high quality chest compressions, and mild cooling—appear to improve long-term survival after cardiac arrest. These interventions affect most the heart and brain, but how these interventions such as cooling "work" in the heart and brain is not known. Recent clinical experience suggests that patients can survive remarkably long periods of cardiac arrest that exceed 30 minutes. These patients return back to work and home neurologically intact if CPR and cooling are optimized. This experience suggests that new approaches that further optimize CPR and cooling treatments could significantly improve public health. This work builds a new collaboration between CPR researchers at the University of Illinois who are studying mechanisms of CPR and cooling protection, and investigators at the University of Chicago who specialize in the development of therapeutic fusion proteins. These proteins are designed to gain rapid access to critical organs rapidly and specifically block endogenous proteins causing disease. We propose to design new proteins that will mimic the effects of cooling in the heart and brain by inhibiting phosphatase enzymes that block tissue survival responses during CPR.