Stroke is the 3rd leading cause of death in the U.S. and is also a leading cause of severe, long-term disability. The total cost of stroke to the United States is estimated at about $43 billion per year. The only FDA-approved treatment for acute ischemic stroke is recombinant tissue plasminogen activator (rt- PA). However, the therapeutic window of rt-PA is only up to 3 hours from onset of stroke, and the treatment may increase the incidence of intracerebral hemorrhage. In the past decade or more, hundreds of neuroprotective compounds have failed in clinical trails due to either their insignificant effectiveness or high toxicity. SynZyme Technologies, LLC, has developed a novel therapy, polynitroxylated albumin (PNA). PNA is synthesized by covalently labeling human serum albumin with a high molar ratio of nitroxides, which act as neurovascular protectants and potent antioxidants. PNA has been tested in a number of leading stroke research centers in the U.S. and showed great promise in various animal stroke models. The feasibility of PNA treatment is confirmed not only by its promising pre-clinical results and its good safety profile, but also by previous clinical trial experience involving either antioxidants alone or those involving human albumin alone. The extensive research efforts are leading PNA into the drug development phase as a treatment of acute ischemic and hemorrhagic stroke. We received clear recommendations from the FDA on PNA development on May 6, 2004. The goal of this proposed work is to complete the requirements of the FDA for an Investigational New Drug (IND) application, an essential step to new drug approval. There are three major components for the completion: chemistry manufacturing and control (CMC), GLP toxicity studies, and clinical protocol development. SynZyme's team will manage and work with high quality certified contract research organizations (CRO) to achieve the proposed Aims according to the FDA's guidance. The completion of IND application will lead to human clinical trials.
