SUPEROXIDE DISMUTASE MIMETICS FOR MANAGEMENT OF PAIN

最近对几种疼痛模型的研究表明，使用Metore专有的超氧化物歧化酶模拟物可以显著降低疼痛反应。其中，M40403是一种具有体内稳定性的高活性和选择性的SOD催化剂，在减轻疼痛反应方面非常有效。基于我们的观察，超氧化物歧化酶可能在各种原因的疼痛中发挥关键作用，并且这种选择性的SOD催化剂确实可以减轻疼痛，我们建议开发一种M40403类的SOD模拟物，作为一种新型的非麻醉性非麻醉性止痛药，用于治疗疼痛。考虑到对更好的疼痛管理的需求和我们研究结果的新颖性，我们建议将该计划积极推进到临床，并因此提交这笔赠款，以考虑作为快速通道I/II阶段的赠款。第一阶段的重点是继续发展我们对超氧化物歧化酶在疼痛中作用的机制的理解，评估第二种超氧化物歧化酶模拟物在疼痛模型中的作用，确定我们的超氧化物歧化酶模拟物与阿片类药物和非类固醇抗炎药物协同作用用于止痛的潜在临床优势，并探索超氧化物歧化酶模拟物在疼痛治疗中的潜力。拟议的商业应用：疼痛市场由具有重大局限性的产品服务，导致严重的用药不足。即将出台的联邦立法《疼痛缓解促进法》旨在鼓励医生更积极地治疗疼痛，提供法律保护，防止意外的副作用。这鼓励了副作用减少的新型止痛药的开发。初步的动物实验表明，超氧化物歧化酶模拟物具有新颖而强大的止痛特性，这让人期待这些化合物具有非常大的商业潜力。

Recent studies in several models of pain have shown that significant reduction in the pain response can be achieved using MetaPhore's proprietary SuperOxide Dismutase mimetics. One of these, M40403, a highly active and selective SOD catalyst possessing 'in vivo' stability, is highly effective in attenuating the pain response. Baked on our observations that superoxide may play a critical role in pain of various etiologies and that such selective SOD catalysts do attenuate pain, we propose to develop a SOD mimetic of the M40403 class as a novel parenteral non-narcotic analgesic for the treatment of pain. Given the need for better pain management and the novel nature of our findings, we propose to move the program aggressively forward to the clinic and are, consequently, submitting this grant for consideration as a fast track Phase I/II grant. The Phase I portion is focused on continuing to develop our mechanistic understanding of the role of superoxide in pain, to evaluate a second SOD mimetic in pain models, to determine the potential clinical advantage of synergistic interaction of our SOD mimetics with opiates and non-steroidal anti-inflammatory drugs for pain relief, and to explore the potential of the SOD mimetics for pain management. PROPOSED COMMERCIAL APPLICATIONS: The pain market is served by products with major limitations, leading to serious undermedication. Pending federal legislation, the 'Pain Relief Promotion Act', is designed to encourage physicians to treat pain more aggressively by providing legal protection from unintended side effects. This encourages the development of novel pain medications with reduced side effects. Initial animal tests show that SOD mimetics have novel and powerful analgesic properties giving rise to expectations that these compounds have very large commercial potential.