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：肺炎是全球死亡的主要原因。即使在发达国家，它仍然是感染导致死亡的主要原因，也是对其他疾病治疗的患者的严重并发症。当宿主抗性水平降低（例如免疫功能低下的癌症患者）以及病原体暴露水平升高时（例如大流行病，生物疗法和生物乳化病）时，肺部感染的威胁会升高。急性白血病患者目前是最高风险的患者，因为他们的癌症治疗面临着明显的免疫功能低下。很多时候，这些风险阻止了完整的癌症治疗计划。结果，每年估计有44,700名白血病患者在一系列治疗上花费超过八亿美元，以预防肺炎。 PulMotect的解决方案：PulMotect已确定并正在开发一种新技术来解决吸入微生物的风险。我们的治疗性（PUL-042）是两种TLR配体的组合，这些配体刺激了肺部自身的天生防御机制，以创造一种敌对的病原体环境，并减少或防止感染。在体外和体内实验都已经完成，以验证这项技术。重要的是，由于细胞转变率低，肺上皮对化疗药物有抵抗力，因此先天免疫反应仍然完好无损。正是在这些大多数高危患者中，可以为其他市场捕获概念验证。该提案的重点是实现将验证该技术进行商业化的关键里程碑。该SBIR应用的重点是解决重要的临床前重要问题。包括的三个目标旨在验证和扩展已经获得的概念验证数据。目的是将该技术转移到诊所。实现这些里程碑将为安全有效的产品提供重要数据。该阶段I提案的积极结果可能会导致第二阶段SBIR在第二种动物模型中对治疗进行深入研究，包括FDA批准的安全性和毒性研究。此外，通过证明PulMotect管道中的后续发现，可以更好地追求投资者的额外外部资金，以将该技术转变为诊所和市场。总体而言，该提案的概述里程碑将以先前的工作为基础，增加该平台技术的基础，并帮助将该技术带到诊所。 ） 公共卫生相关性：Pulmotect，Inc正在开发新型的治疗剂，这些治疗剂刺激先天免疫系统以防止传染病，即使在严重损害免疫力的情况下也是如此。概念证明数据表明，该技术有效地保护了广泛的吸入病原体。该项目将提供重要的数据，以帮助将该技术从实验室过渡到诊所，医生要求使用该技术使患者受益。