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

这个小型企业创新研究(SBIR)第一阶段项目的更广泛影响是减轻过度炎症造成的痛苦。过度炎症是一种免疫系统的失调，通常由病毒性肺炎引起。它可能会有严重的危及生命的并发症，包括急性呼吸窘迫综合征和血液凝固的变化；新冠肺炎患者中已经出现了高炎症。由过度炎症引起的继发性疾病也可能对患者的健康造成严重的长期后果。该项目将开发治疗方法，平息免疫系统的系统性失调，降低患者死亡率。拟议中的项目将推进对新冠肺炎引发的炎症等过度炎症的治疗。它由多种刺激引起，并导致危及生命的免疫系统的错误调节。通过一个新的分子靶点，一类新的抗纤维化化合物具有降低细胞因子水平和促凝血因子的潜力，广泛地作用于解决炎症反应的异质性。随着新冠肺炎诱导的细胞因子风暴的相关信息的获得，相关的生物标记物已经被提出。为了展示对炎症的强大作用，该项目将评估该疗法对1)促炎症细胞因子的释放，2)天然免疫系统的激活，以及3)炎症开始后全身细胞因子和促凝血因子的浓度的影响。将建立生物标记物来跟踪治疗炎症早期和晚期的疗效，为在炎症动物模型中测试这类化合物的有效性提供了强有力的理论依据。重要的是，随着这个项目的成功完成，这类疗法将展示出治疗炎症过度的潜力，以及证明有能力预防肺纤维化，这是一种潜在的致命并发症。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.