Rutgers University CounterACT Center of Excellence

Abstract This is a renewal application for the Rutgers University CounterACT Research Center of Excellence, leaders in the discovery and development of drugs to treat poisoning from exposure to chemical threat agents. The Center focuses on vesicants including sulfur mustard, nitrogen mustard, and other mechanistically related chemicals and is organized into three Research and Development Projects, each focused on a major vesicant target: the skin, the cornea and the lung. The overall goal of the Center is to identify specific targets in these tissues that can be used for therapeutic intervention. To accomplish this goal, mechanistic research using appropriate translational models for the skin, cornea and lung is being performed by scientific experts in each of these areas. The Research and Development Projects are supported by a Pharmacology and Drug Development Scientific Support Core and a Pharmaceutics and Medicinal Chemistry Scientific Support Core, each consisting of investigators with considerable expertise in drug discovery, delivery and development. Through mechanistic research, the Rutgers Center has 1) discovered and prioritized several efficacious lead compounds and 2) developed innovative formulations and delivery systems that augment pharmacological activity and improve pharmacokinetic profiles. Three lead compounds, two for mustard-induced ocular injury and another for mustard-induced lung injury, are FDA approved for other indications, and are being advanced for use as mustard countermeasures. Furthermore, IND-enabling studies have been completed on a lead compound discovered to be effective against mustard-induced skin injury. The Rutgers CounterACT Center has established strategic corporate partnerships for advanced drug development with lead compounds and support by BARDA. A Research Education Core directed at students, postdoctoral trainees, technical staff, and new and established investigators has been highly successful at training a skilled workforce in countermeasures. During the next grant period, we will 1) identify and develop second generation drug products with improved effectiveness, 2) disseminate key findings about mechanisms of toxicity and novel testing strategies and models, 3) advance current drug leads through the FDA approval process and 4) expand training and workforce development opportunities. By meeting key research, development, and training milestones, the Center is well-poised to advance new and repurposed drugs through the approval process for treating vesicant poisoning in humans.