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

STTR 第一阶段：聚合物表面活性剂治疗急性呼吸窘迫综合征（COVID-19）

• 批准号: 2036125
• 负责人: Davis Arick
• 金额: $ 25.6万
• 依托单位: SPIRO THERAPEUTICS LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2036125&HistoricalAwards=false
• 关键词: STTR; Phase; Polymer; Surfactant; Therapy

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.

该小企业技术转让（STTR）I期项目的更广泛影响/商业潜力将是开发一种用于治疗急性呼吸窘迫综合征（ARDS）以及其他潜在严重呼吸系统疾病的首个同类治疗药物，这些疾病的特征是高死亡率、发病率和住院时间。ARDS导致肺表面活性剂失活，而肺表面活性剂负责保持肺结构膨胀和干燥。这会导致血氧不足和多器官衰竭，而无需有创机械通气。据信，ARDS占世界ICU床位的7%，并且可以由许多根本原因引起，包括直接肺损伤（即细菌/病毒性肺炎）和间接肺损伤（即创伤）。就疫情而言，现有数据显示，14%的COVID-19病例需要住院治疗。在这些患者中，三分之一的人会发展为ARDS，使他们的生存机会降低到60%。在正常年份，全球有300万例ARDS病例（220 k US），这些病例是高度资源密集型的（平均8.2万美元的治疗费用），这给患者和医疗保健系统带来了相当大的经济负担。治疗性治疗将减少患者死亡和慢性并发症的发生率。拟议的项目将通过合成聚合物肺表面活性剂（PLS）技术开发一种不同的ARDS治疗方法。这种PLS技术克服了以前尝试的疗法的缺点，因为它被设计成可安全地用于体内，具有高度表面活性（较低的表面张力），水溶性（在可注射的水性悬浮液中制备），并且抗蛋白质失活。悬浮在溶液中，PLS均匀分布在机械通气患者的肺部。当PLS到达肺泡时，它形成了一个可透气的胶束单层，模拟人肺表面活性剂的功能，而不会被灭活。 这样做可以使肺泡重新充气，同时减少液体积聚和炎症，从而恢复血液氧合。基于有前景的PLS安全性/有效性概念验证数据，该项目的具体目标#1将优化因不同根本原因（感染与酸吸入）诱导的ARDS小鼠的给药参数。具体目标#2将使用碘标记的PLS来生成从递送到处理后几天的小鼠中的分布和清除数据。这些数据将用于优化关键的交付和PLS参数，以确保最大的功效持续数天。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。