SOD/CATALASE MIMIC TO PREVENT SKIN DAMAGE IN RADIATION T

接受电离辐射治疗的癌症患者受到正常组织损伤的影响，可能在治疗后几天到几周，甚至几个月到几年。根据场地和其他因素的不同，这种损害的严重程度可能从不适到剂量限制和虚弱，再到危及生命。在电离辐射后组织损伤的几个阶段都涉及到活性氧物种(ROS)。Eukarion已经开发出一类分子Salen锰络合物，它是抗氧化酶超氧化物歧化酶(SOD)和过氧化氢酶的合成模拟物，在ROS诱导的病理模型中具有保护作用，包括辐射诱导的组织损伤。该公司计划开发这些化合物作为辐射防护剂，第一个临床适应症是一种皮肤病制剂，用于预防乳腺癌患者的辐射引起的皮肤损伤。该SBIR项目涉及关键的临床前研究，这将使Eukarion能够向食品和药物管理局(FDA)提交研究新药(IND)申请，以便开始临床试验。对于第二阶段，具体目标是：(1)开发生产皮肤病产品的放大方法；(2)评估铅分子安全性的毒性研究；(3)针对配方的毒性研究，评估皮肤病产品的安全性；(4)研究铅分子和皮肤病产品的生物分布。建议的商业应用本研究的重点是提供保护癌症患者免受电离辐射治疗的破坏性副作用的产品。这种特定的焦点是一种皮肤科产品，用于预防乳腺癌患者的皮肤损害。每年约有18万新的乳腺癌病例，其中约65%接受放射治疗。在这些人中，几乎所有人都会出现急性皮肤损伤，约20%的人受损严重，许多人遭受长期损伤，如纤维化。目前还没有预防这种皮肤损伤的治疗方法。

Cancer patients treated with ionizing radiation are subject to normal tissue damage that can occur days to weeks, or even months to years after treatment. Depending on the site and other factors, the severity of this damage can range from uncomfortable to dose-limiting and debilitating, to life-threatening. Reactive oxygen species (ROS) are implicated at several stages of tissue injury following ionizing radiation. Eukarion has developed a class of molecules, salen manganese complexes, that are synthetic mimetics of the antioxidant enzymes superoxide dismutase (SOD) and catalase and are protective in models for ROS-induced pathologies, including radiation induced tissue injury. The company plans to undertake the development of these compounds as radioprotectors, with the first clinical indication to be a dermatological preparation to prevent radiation-induced skin damage in breast cancer patients. This SBIR project involves key preclinical studies that will enable Eukarion to file an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) in order to begin clinical trials. For Phase II, the Specific Aims are: (1) Development of scale-up methods to manufacture the dermatological product; (2) Toxicity studies to assess the safety of the lead molecule; (3) Formulation-specific toxicity studies, to assess the safety of the dermatological product; (4) Studies to examine the biodistribution of the lead molecule and dermatological product. PROPOSED COMMERCIAL APPLICATION This research is focused on providing products to protect cancer patients from the damaging side-effects of ionizing radiation therapy. The specific focus is a dermatological product to prevent skin damage in breast cancer patients. Each year, there are about 180,000 new cases of breast cancer, and about 65 percent are treated with radiation. Of these, virtually all develop acute skin damage, with about 20 percent damaged severely and with many suffering longer term damage such as fibrosis. There are no current therapies for preventing this skin damage.