Rapidly boosting innate immunity in the lungs to protect against pneumonia

快速增强肺部的先天免疫力以预防肺炎

• 批准号: 8056839
• 负责人: Brenton Scott
• 金额: $ 22.17万
• 依托单位: PULMOTECT, INC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056839
• 关键词: Acute leukemia; Address; Aftercare; Animal Model; Biological Markers; Biological Warfare; Blood; Breathing; Cancer Patient; Cause of Death; Cells; Clinic; Communicable Diseases; Complication; Consultations; Cytarabine; Data; Data Set; Defense Mechanisms; Developed Countries; Development; Disease; Dose; Environment; Epithelial; Epithelium; FDA approved; Foundations; Funding; Host resistance; Immune response; Immune system; Immunity; Immunocompetent; Immunocompromised Host; In Vitro; Infection; Infection prevention; Inflammation; Irrigation; Lead; Ligands; Liquid substance; Lung; Lung Inflammation; Lung Lavage Fluid; Marketing; Measures; Microbe; Mus; Natural Immunity; Patients; Permeability; Pharmaceutical Preparations; Phase; Physicians; Pneumonia; Preparation; Published Comment; Resistance; Respiratory physiology; Risk; Safety; Small Business Innovation Research Grant; Solutions; Sputum; Technology; Therapeutic; Time; Toxic effect; Work; aerosolized; airway hyperresponsiveness; cancer therapy; chemotherapeutic agent; chemotherapy; commercialization; cytokine; design; follow-up; in vivo; leukemia; meetings; microbial; new technology; novel therapeutics; pandemic disease; pathogen; pathogen exposure; pre-clinical; prevent; research study; treatment planning

DESCRIPTION (provided by applicant): Problem: Pneumonia is the leading cause of death worldwide. Even in developed countries, it continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times these risks prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two TLR ligands that stimulate the lung's own innate defense mechanisms to create a hostile environment for pathogens and reduce or prevent infection. Both in vitro and in vivo experiments have been completed to validate this technology. Importantly, because of the low cell-turnover rate, the lung epithelium is resistant to chemotherapy drugs so the innate immune response remains intact. It is in these most at-risk patients where proof-of-concept can be captured for additional markets. The focus of this proposal is to accomplish key milestones that will validate this technology for commercialization. This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic. ) PUBLIC HEALTH RELEVANCE: Pulmotect, Inc is developing novel therapeutics that stimulates the innate immune system to protect against infectious diseases, even in cases of severely compromised immunity. Proof-of-concept data has shown that this technology effectively protects against a broad range of inhaled pathogens. This project will provide significant data to help transition this technology from the lab to the clinic, where physicians are asking to use the technology to benefit their patients.

描述（由申请人提供）： 问题：肺炎是全世界死亡的主要原因。即使在发达国家，它仍然是感染死亡的主要原因，也是接受其他疾病治疗的患者的严重并发症。当宿主抵抗力水平降低（例如免疫功能低下的癌症患者）以及病原体暴露水平增加（例如流行病、生物恐怖和生物战）时，肺部感染的威胁就会增加。急性白血病患者目前是高危患者之一，因为他们面临着因癌症治疗而导致的严重免疫功能低下。很多时候，这些风险会阻碍完整的癌症治疗计划的完成。因此，每年估计有 44,700 名白血病患者花费超过 5 亿美元用于预防肺炎的一系列治疗。 Pulmotect 的解决方案：Pulmotect 已经确定并正在开发一种新技术来解决吸入微生物的风险。我们的治疗药物 (PUL-042) 是两种 TLR 配体的组合，可刺激肺部自身的先天防御机制，为病原体创造一个不利的环境，并减少或预防感染。体外和体内实验均已完成以验证该技术。重要的是，由于细胞周转率低，肺上皮对化疗药物具有抵抗力，因此先天免疫反应保持完整。正是在这些风险最高的患者中，可以为其他市场获得概念验证。该提案的重点是实现关键里程碑，验证该技术的商业化。该 SBIR 应用程序专注于解决重要的临床前重要问题。所包含的三个目标旨在验证和扩展已获得的概念验证数据。目标集中于将该技术转化为临床。实现这些里程碑将为安全有效的产品的 IND 申请提供重要数据。这一 I 期提案的积极结果可能会导致 II 期 SBIR 申请，以在第二种动物模型中对该疗法进行深入研究，包括 FDA 批准的安全性和毒性研究。此外，通过展示 Pulmotect 研发管线中的后续发现，可以更好地寻求投资者的额外外部资金，将该技术转化为临床和市场。总体而言，该提案概述的里程碑将建立在以前的工作基础上，增加该平台技术的基础，并有助于将该技术推向临床。 ） 公共健康相关性：Pulmotect, Inc 正在开发新的疗法，即使在免疫力严重受损的情况下，也能刺激先天免疫系统以预防传染病。概念验证数据表明，该技术可以有效防止多种吸入病原体。该项目将提供重要数据，帮助将该技术从实验室转移到临床，医生要求使用该技术造福患者。