SODm for Management of Ischemic Heart Disease

描述(申请人提供)：心脏模型的最新研究 缺血/再灌流损伤已显示组织明显减少 脑梗塞的损害可以使用MARMERS的专有超氧化物来实现 歧化酶模拟(SODm)。在初步研究中，我们发现M40403a 选择性和强效的SODm保留了心脏功能 缺血/再灌注损伤。根据自由基生成的数据， 尤其是超氧化物，可能在介导组织损伤和 心脏缺血事件后的死亡，如心脏病发作，我们建议 开发一种模拟M40403类的SODm作为一种新型的注射用药 心肌梗死或缺血后给药。M40403将不会 为这一适应症而开发的，其原因在提案中讨论。 取而代之的是M40401，具有更高的催化活性，相似的稳定性和 将致力于改善M40403的毒性。考虑到巨大的需求 改善心肌缺血和梗死的预后，新的发现 这些SODm在保护组织免受缺血/再灌流损伤中的作用 伤害，以及这类药物对当前管理的潜在影响 在这个国家，我们建议积极推进该计划 正在等待临床应用，因此，我们提交了这项提案 对价。第一阶段的应用程序专注于开发我们的机械 超氧化物歧化酶在心肌缺血/再灌注损伤中的作用 并评价M40401对心肌缺血的保护作用 并探讨该药在脑缺血后处理中的潜在应用。 心脏病。 建议的商业应用：不可用

DESCRIPTION (provided by applicant): Recent studies in models of cardiac ischemia/reperfusion injury have shown that a significant reduction in tissue damage from infarction can be achieved using MetaPhor's proprietary superoxide dismutase mimetics (SODm). In preliminary studies we found that M40403 a selective and potent SODm preserved cardiac function following ischemia/reperfusion injury. Based on the data that free radical generation, especially superoxide, may play a critical role in mediating tissue damage and death in heart following an ischemic event, such as a heart attack, we propose to develop a SODm mimetic of the M40403 class as a novel parenteral agent for administration after cardiac infarction or ischemia. M40403 will not be developed for this indication for reasons that are discussed in the proposal. Instead M40401, an SODm with higher catalytic activity, similar stability and improved toxicity to M40403 will be pursued. Given the enormous need for improving the outcome of cardiac ischemia and infarction, the novel findings of these SODm in protecting tissues from damage following ischemia/reperfusion injury, and the potential impact of this class of drugs on current management of heart disease in this country, we propose to move the program aggressively forward to clinical application and thus, are submitting this proposal for consideration. The Phase I application is focused on developing our mechanistic understanding of the role of superoxide in cardiac ischemia/reperfusion injury and to evaluate the effects of M40401 in protection against cardiac ischemia and to explore the potential use of this drug in post-ischemia management of heart disease. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE