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.
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.