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

这个小企业创新研究（SBIR）第一阶段项目的更广泛影响是减轻由过度炎症引起的痛苦。高度炎症是一种免疫系统的失调，通常由病毒性肺炎引起。它可能导致严重的危及生命的并发症，包括急性呼吸窘迫综合征（ARDS）和凝血变化；在COVID-19患者中发现了高度炎症。由高度炎症引起的继发性疾病也可能对患者健康产生严重的长期后果。该项目将开发治疗方法，以平息免疫系统的系统性失调，并降低患者死亡率。该项目将推进新型冠状病毒感染症（COVID-19）引起的高度炎症的治疗方法。它由多种刺激引起，并导致危及生命的免疫系统失调。随着新的分子靶点，一类新的抗纤维化化合物具有降低细胞因子水平和凝血因子的潜力，广泛作用于解决炎症反应的异质性。随着COVID-19诱导的细胞因子风暴的信息越来越多，相关的生物标志物被提出。为了证明对炎症的强大作用，该项目将评估治疗对以下方面的影响：1)促炎细胞因子释放，2)先天免疫系统的激活，以及3)炎症开始后细胞因子和凝血因子的全身浓度。将建立生物标志物来跟踪炎症早期和晚期治疗的疗效，为在动物炎症模型中测试这类化合物的疗效提供有力的依据。重要的是，随着该项目的成功完成，这类疗法将被证明具有治疗高度炎症的潜力，同时具有预防肺纤维化（一种潜在的致命并发症）的能力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.