LignaMed, LLC is a drug development company with a fast track strategy to approval of LGM2605, an oral small molecule for use as a radiation mitigating agent that reduces harmful effects of radiation exposure of normal tissues. LignaMed aims to evaluate LGM2605 as a mitigator of space-radiation induced vascular damage. NASA missions to Mars will expose astronauts to solar and galactic cosmic mixed radiation including low dose ? and proton radiation, but data is lacking on the biological and physiological effects in humans of this mixed source radiation. Research on space radiation effects on cellular systems, molecular targets and ultimately organ systems has identified potential harmful short and long-term effects on the health of astronauts. Work at the University of Pennsylvania identified damage to lungs years after a single exposure to low-dose gamma, 56Fe, 28Si and proton radiation exposure in mice. Acute and chronic radiation effects in organs are closely associated with vascular damage and dysfunction. Multiple studies have confirmed single source radiation side effects associated with significant loss of vascular integrity: increased vascular leakiness (edema), an activated inflammatory phenotype and extensive oxidative damage. However, damage to the vascular network under multiple radiation types simultaneously is not understood. LignaMed will employ gene knockout technology in vascular models exposed to space-relevant mixed radiation regimens to investigate the injury to the vasculature. We hypothesize that LGM2605 will mitigate space radiation-induced vascular damage by inhibiting early events that cause inflammation. This study will confirm that 1) space radiation drives endovascular damage via activation of the endothelial inflammatory phenotype resulting in increased permeability and 2) will validate LGM2605 as an effective mitigator of space radiation-induced vascular damage by inhibiting early events that drive long term adverse sequellae.
Potential NASA Commercial Applications: (Limit 1500 characters, approximately 150 words) LignaMed, LLC is a drug development company with a fast track strategy to approval of LGM2605, an oral small molecule for use as a radiation mitigating agent that reduces harmful effects of radiation exposure of normal tissues. LignaMed, in collaboration with researchers at University of Pennsylvania, plans to identify the detrimental biochemical signals activated with space radiation and evaluate their mitigation by LGM2605. Manned missions to Mars will expose astronauts to solar and galactic cosmic radiation in the form of low dose ? radiation as well as high dose protons from solar particle events (2-4). A mixed radiation environment is unique to space and does not exist on earth and there is a lack of data on space radiation induced biological effects and thus inadequate resources of countermeasures (5). We propose to identify the pathways that lead to injury and damage from space radiation. Inflammation is one of the earliest triggers for tissue damage and an underlying cause of several pathologies including radiation induced diseases. The vasculature is an initiating and converging site of inflammation which is followed by extravasation into tissue and tissue injury. Although radiation-induced damage is largely in the form of circulatory problems, vascular damage in response to space radiation in particular, has never been investigated and due to its unique mechanism, LGM2605 has the potential to mitigate these negative effects of space travel related radiation.
Potential NON-NASA Commercial Applications: (Limit 1500 characters, approximately 150 words) Lignamed LLC is a biopharmaceutical company developing LGM-2605 as adjunct therapy to reduce side effects and improve cure rates of radiation treatment of chest cancers. The market size is $5 billion. Chest cancers are a deadly and costly disease. They include breast cancer, lung cancer, sarcomas, lymphomas and esophageal cancer. According to the American Cancer Society, more than 500,000 new chest cancer cases will be diagnosed in the United States in 2014 and they project the number to increase in the years ahead. About 50 to 60 percent of cancer patients are treated with radiation at some time during their disease. Combinations of surgery, chemotherapy and radiation treatments are the standard for modern cancer therapy. Success is often determined by the ability of patients to tolerate the most aggressive regimen. The ability to deliver effective radiation therapy is limited by toxic side effects to healthy normal lung tissues. These side effects often cause breaks in treatment or dose-limiting toxicity after treatment, and, therefore, limit the amount of radiation that can be delivered to the tumor. No current therapies are effective to protect healthy normal lung tissue from the damaging effects of radiotherapy. A significant unmet need exists for a safe radioprotection agent that will ameliorate radiation side effects to normal tissue without "protecting" the tumor. The US market opportunity is estimated at $5 billion per year.
Technology Taxonomy Mapping: (NASA's technology taxonomy has been developed by the SBIR-STTR program to disseminate awareness of proposed and awarded R/R&D in the agency. It is a listing of over 100 technologies, sorted into broad categories, of interest to NASA.) Physiological/Psychological Countermeasures
