Protein Transduction Therapy for ARDS

Since acute lung injury (ALI) develops rapidly, fast-acting pharmaco-specific therapy is required to prevent acute respiratory distress syndrome (ARDS) and mortality. We developed a novel biologic (U.S. Patent WO2009046129-A2) that can strengthen the endothelial barrier via protein-protein interaction. The proposal is to load lung endothelium with a purified, phosphorylated form of focal adhesion kinase that is conjugated with the cell-permeable peptide, TAT, to induce barrier enhancing protein-protein interactions that will protect against acute lung injury ALI/ARDS. Intravenous protein transduction could prevent pre- or post-lung injury. Given immediately after injury, as for example after trauma, our biologic could ameliorate pulmonary edema. Given as multiple repeat doses every 4-8 hours, biologic could improve morbidity in endotoxin-induced ALI/ARDS. These findings are likely to impact understanding of molecular mechanisms of ALI/ARDS lead to novel therapeutic strategies for the treatment of ALI/ARDS and other inflammatory lung diseases.