Neuregulin-1 beta (NRG-1) is a growth and survival factor in several organ systems, and is critical for cardiac development. In the adult heart NRG-1 is a stress-activated mediator of cardiac repair after injury. Parenteral administration of recombinant NRG-1 enhances survival and improves cardiac function in chemotherapeutic, viral, myocardial infarction (Ml) and rapid-pacing induced heart failure models in mouse, rat and dog. Acorda Therapeutics owns the recombinant NRG-1 Glial Growth Factor 2 (GGF2) which is being developed for treatment of heart failure and demyelinating diseases. The central hypothesis of this proposal is that GGF2 can be used to treat systolic heart failure. In this stage 1 CTRIP proposal, we are partnering with Acorda Therapeutics to advance this effort. Acorda has completed safety studies of GGF2 in small and large animals, and plans to submit an IND for use of GGF2 in treatment of systolic heart failure. Critical animal work is necessary to determine minimal effective dose of GGF2 for cardiac recovery after myocardial infarction. Further work in small and large animals will be carried out to develop noninvasive imaging strategies to determine biological effects of GGF2 in the myocardium. Following successful IND submission, we will carry out a phase 1 human trial in persons with systolic heart failure. Noninvasive imaging and peripheral biomarker studies will be examined in conjunction with the phase 1 trial to determine minimal biologically efficacious dose. We have brought together a team of consultants from four Institutions to help guide the planning of a multicenter randomized placebo controlled study to be proposed for the stage 2 application that will test the hypothesis that GGF2 will induce sustained improvements in cardiac function in persons with systolic heart failure. RELEVANCE (See instructions): Heart failure is a common condition that results in chronic illness and early death, and is often caused by weakening of the heart. We propose to carry out a series of experiments, including a safety study in people with a new therapy for weak heart muscles. If successful this therapy has the potential to save the lives of people with heart failure.