SBIR Phase I: Quieting systemic hyper-inflammation (COVID-19)

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to alleviate the suffering caused by hyper-inflammation. Hyper-inflammation is a mis-regulation of the immune system often brought on by viral pneumonia. It can have severe life-threatening complications, including acute respiratory distress syndrome (ARDS) and changes in blood clotting; hyper-inflammation has been seen in COVID-19 patients. Secondary conditions caused by hyper-inflammation can also have severe long-term consequences to patient health. This project will develop therapeutics that quiet the systemic mis-regulation of the immune system and reduce patient mortality. The proposed project will advance a treatment for hyper-inflammation, such as that induced by COVID-19. It arises from multiple stimuli and results in life-threatening mis-regulation of the immune system. With a novel molecular target, a new class of anti-fibrotic compounds have the potential to reduce cytokine levels and pro-coagulation factors, acting broadly to address the heterogeneity of inflammation responses. As information becomes available regarding the cytokine storm induced by COVID-19, relevant biomarkers have been proposed. To demonstrate robust actions on inflammation this project will evaluate the effects of the therapeutic on 1) pro-inflammatory cytokine release, 2) activation of the innate immune system, and 3) systemic concentrations of cytokines and pro-coagulation factors after initiation of inflammation. Biomarkers will be established to track the efficacy of the therapeutic at early and late stages of inflammation, providing a strong rationale for testing the efficacy of this class of compounds in animal models of inflammation. Importantly, with the successful completion of this project, this class of therapeutics will have demonstrated potential to treat hyper-inflammation, coupled with a demonstrated ability to prevent pulmonary fibrosis, a potentially fatal complication. 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.