Recombinant Neuregulin for the treatment of Heart Failure

描述（由申请人提供）： Neuregulin-1 beta（NRG-1）是多种器官系统中的生长和存活因子，对心脏发育至关重要。在成人心脏中，NRG-1是损伤后心脏修复的应激激活介质。重组NRG-1的肠胃外给药在小鼠、大鼠和狗的化疗、病毒、心肌梗死（MI）和快速起搏诱导的心力衰竭模型中增强存活并改善心脏功能。Acorda Therapeutics拥有重组NRG-1神经胶质生长因子2（GGF 2），正在开发用于治疗心力衰竭和脱髓鞘疾病。该提议的中心假设是GGF 2可用于治疗收缩性心力衰竭。在第一阶段的CTRIP提案中，我们与Acorda Therapeutics合作推进这一工作。Acorda已经完成了GGF 2在小型和大型动物中的安全性研究，并计划提交使用GGF 2治疗收缩性心力衰竭的IND。关键的动物工作是必要的，以确定最低有效剂量的GGF 2心肌梗死后心脏恢复。将在小型和大型动物中开展进一步的工作，以开发非侵入性成像策略，以确定GGF 2在心肌中的生物学效应。在成功提交IND后，我们将在收缩性心力衰竭患者中进行1期人体试验。将结合I期试验检查无创成像和外周生物标志物研究，以确定最小生物学有效剂量。我们召集了来自四个机构的顾问团队，以帮助指导计划一项多中心随机安慰剂对照研究，该研究将用于第2阶段申请，该研究将测试GGF 2将诱导收缩性心力衰竭患者心脏功能持续改善的假设。 相关性（参见说明）：心力衰竭是一种常见的疾病，导致慢性疾病和过早死亡，通常是由心脏衰弱引起的。我们计划进行一系列的实验，包括一项针对心肌衰弱患者的安全性研究。如果成功，这种疗法有可能挽救心力衰竭患者的生命。

DESCRIPTION (provided by applicant): 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.