SODm for Management of Ischemic Heart Disease

描述（由申请人提供）：心脏模型的最新研究 局部缺血/再灌注损伤已经表明， 梗塞的损害可以通过使用MetaPhor专有的超氧化物来实现 歧化酶模拟物（SODm）。在初步研究中，我们发现M40403 a 选择性和有效的SODm保留心脏功能， 缺血/再灌注损伤基于自由基产生的数据， 特别是超氧化物，可能在介导组织损伤中起关键作用， 我们建议，在缺血性事件（如心脏病发作）后， 开发M40403类的SODm模拟物作为新型胃肠外药物， 在心肌梗塞或局部缺血后施用。M40403不会 出于提案中讨论的原因，针对该适应症开发。 代替M40401，具有更高的催化活性、相似的稳定性和 将寻求改善对M40403的毒性。鉴于对 改善心肌缺血和梗死的结局， 这些SODm在保护组织免受缺血/再灌注损伤中的作用 损伤，以及该类药物对当前管理的潜在影响 心脏病的发病率，我们建议积极地 即将进入临床应用，因此提交此提案， 考虑.第一阶段应用程序的重点是开发我们的机械 超氧化物在心肌缺血/再灌注损伤中的作用 评价M40401对心肌缺血的保护作用 并探索这种药物在缺血后管理中的潜在用途， 心脏病 拟议商业应用：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