STTR Phase I: Polymer Surfactant Therapy for Acute Respiratory Distress Syndrome (COVID-19)

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project will be to develop a first-in-kind therapeutic for treatment of Acute Respiratory Distress Syndrome (ARDS) as well as potentially other severe respiratory conditions that are characterized by high rates of mortality, morbidity, and hospitalization time. ARDS causes deactivation of the lungs’ surfactant, which is responsible for keeping the lung structure inflated and dry. This causes inadequate blood oxygenation and mutli-organ failure without invasive mechanical ventilation. ARDS is believed to account for 7% of the world’s ICU beds and can be caused by many root causes, including both direct lung injuries (i.e. bacterial/viral pneumonia) and indirect lung injuries (i.e. trauma). In the case of the pandemic, current data suggests that 14% of COVID-19 cases require hospitalization. Of these patients, 1 in 3 will develop ARDS, reducing their chance of survival to 60%. In a normal year there are 3 million ARDS cases globally (220k US) that are highly resource intensive (avg. $82k treatment cost), which presents a considerable financial burden on patients and healthcare systems. A therapeutic treatment would reduce patient deaths and frequency of chronic complications. The proposed project will develop a different approach to ARDS treatment via a synthetic Polymer Lung Surfactant (PLS) technology. This PLS technology overcomes shortcomings of previously attempted therapies as it is engineered to be safely used in the body, highly surface-active (lower surface tension), water-soluble (prepared in injectable aqueous suspension), and resistant to protein deactivation. Suspended in solution, PLS is evenly distributed in the lungs of mechanically ventilated patients. When PLS reaches the alveoli, it forms a gas-permeable micelle monolayer that mimics the function of human lung surfactant without being deactivated. Doing so re-inflates the alveoli while reducing fluid accumulation and inflammation so that blood oxygenation can be restored. Building upon promising PLS safety/efficacy proof-of-concept data, specific aim #1 of this project will optimize delivery parameters in mice that have been induced with ARDS by differing root causes (infection vs. acid-aspiration). Specific aim #2 will use iodine-labeled PLS to generate distribution and clearance data in mice from delivery to several days post-treatment. This data will be used to optimize key delivery and PLS parameters to ensure that maximum efficacy is sustained for several days. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.