SYNTHETIC SOD/CATALASE MIMICS FOR STROKE

中风是美国第三大死亡原因，被认为是成年人残疾的最常见原因。药物干预在预防中风发作后数小时或数天内发生的神经损伤方面几乎没有作用。活性氧（ROS）与这种损伤密切相关。Eukarion已经开发了一系列低分子量的合成化合物，它们是催化ROS清除剂，模仿抗氧化剂超氧化物歧化酶（SOD）和过氧化氢酶，并对啮齿动物中风模型具有高度保护作用。这个SBIR项目将研究这些SOD/过氧化氢酶模拟物在中风中的潜在治疗价值。在第一阶段，研究人员评估了几种化合物在啮齿动物中风模型中的神经保护活性，以及其他相关特性，如溶解度和稳定性。在此基础上，选择了三个化合物作为临床前和临床开发的候选分子。第二阶段的研究将包括：(1)安全性筛选研究，以便选择一种化合物作为先导分子（“EUK-n”）；(2)开发用于临床给药EUK-n的注射制剂；(3)正式的毒性研究；(4)药代动力学和生物分布研究。这将为向FDA提交研究新药申请提供必要的信息，以便启动EUK-n的临床试验。建议的商业应用：在美国，中风每年影响约50万患者，目前还没有令人满意的治疗方法来预防由此导致的神经损伤。Eukarion的新型SOD/过氧化氢酶模拟物在啮齿动物中风模型中具有高度的神经保护作用。这项SBIR研究将提供关键的临床前信息，使Eukarion能够向FDA申请启动SOD/过氧化氢酶模拟物的临床试验许可。

Stroke is the third leading cause of death in the United States and is considered to be the most common cause of adult disability. Pharmacological intervention has made little, if any, impact in preventing neurological damage that occurs during the hours and days following stroke onset. Reactive oxygen species (ROS) are strongly implicated in this damage. Eukarion has developed a series of low molecular weight synthetic compounds that are catalytic ROS scavengers, mimicking the antioxidants superoxide dismutase (SOD) and catalase, and are highly protective in rodent stroke models. This SBIR project will investigate the potential therapeutic value of these SOD/catalase mimics in stroke. During Phase I, several of the compounds were evaluated for their neuroprotective activity in the rodent stroke model, and for other relevant properties such as solubility and stability. Based on this research three compounds were selected as candidate molecules for preclinical and clinical development. Research proposed for Phase II will involve: (l) Safety screening studies to enable selection of one compound as the lead molecule ("EUK-n"); (2) Development of an injectable formulation for clinical administration of EUK-n; (3) Formal toxicity studies; and (4) Pharmacokinetic and biodistribution studies. This will provide necessary information to file an Investigational New Drug application with the FDA in order to initiate clinical trials with EUK-n. PROPOSED COMMERCIAL APPLICATION: Stroke affects about 500,000 patients annually in the U.S. and there is no satisfactory treatment to prevent the neurological darn age that results. Eukarion's novel SOD/catalase mimics are highly neuroprotective in rodent stroke models. This SBIR research will provide key preclinical information that will enable Eukarion to apply to the FDA for permission to initiate clinical trials with an SOD/catalase mimic.