Plasma Gelsolin as Immunotherapeutic for Antibiotic-Resistant Pneumonia

血浆凝溶胶蛋白作为抗生素耐药性肺炎的免疫治疗剂

基本信息

  • 批准号:
    9146035
  • 负责人:
  • 金额:
    $ 93.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-05-19 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

Abstract The Problem: Antibiotic resistance is a serious and increasing threat to public health. The RFA that prompts our proposal encourage “Modulation of host immune response to combat infection and/or reduce disease pathology.” The Proposed Solution: We focus on one specific candidate immunomodulator, plasma gelsolin (pGSN) which will benefit patients with antibiotic- resistant bacterial pneumonias (ARPs) by three distinct mechanisms: 1) enhanced macrophage bacterial killing; 2) clearance of extracellular actin released by lung injury (which inhibits bacterial clearance); and 3) binding/dampening excess pro-inflammatory mediators. Diminished pGSN in blood predicts poor outcome in critically ill patients, and restoration in animal models allows survival from otherwise fatal injuries. This has led to already completed, extensive safety and toxicity evaluation of pGSN as a possible therapeutic for other clinical problems. This groundwork provides a strong start for the main goal of this project: to assess and optimize use of plasma gelsolin (pGSN) as a broad-spectrum immunomodulator to improve treatment of antibiotic-resistant bacterial pneumonias ARPs. The Plan: Aims 1 and 2 will test pGSN for improved outcome in primary and secondary ARP mouse models (Strep. pn, MRSA, and Pseudomonas). We will test post-infection efficacy, alone or in combination with suboptimal antibiotics, analyze drug levels, inflammatory and pathologic parameters in optimized protocols, and compare systemic vs. aerosol delivery routes. Aim 3 will develop a clinical testing ELISA assay for use in human studies. Product development efforts will address formulation, safety and regulatory issues needed to expedite clinical testing upon completion. The Significance & Impact: pGSN is a novel, host-targeted therapeutic that has already passed many safety and regulatory hurdles for clinical use. We expect that this project will establish its utility for infections caused by multiple pathogens, and expedite its translation into the clinic for the growing problem of antibiotic –resistant pneumonia.
摘要

项目成果

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LESTER KOBZIK其他文献

LESTER KOBZIK的其他文献

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{{ truncateString('LESTER KOBZIK', 18)}}的其他基金

Plasma Gelsolin as Immunotherapeutic for Antibiotic-Resistant Pneumonia
血浆凝溶胶蛋白作为抗生素耐药性肺炎的免疫治疗剂
  • 批准号:
    9275351
  • 财政年份:
    2016
  • 资助金额:
    $ 93.94万
  • 项目类别:
2014 Biology of Acute Respiratory Infection Gordon Research Conference and Semina
2014年急性呼吸道感染生物学戈登研究会议及研讨会
  • 批准号:
    8650427
  • 财政年份:
    2014
  • 资助金额:
    $ 93.94万
  • 项目类别:
Transgenerational Susceptibility to Asthma from Air Pollution Exposure
空气污染暴露对哮喘的跨代易感性
  • 批准号:
    8598612
  • 财政年份:
    2013
  • 资助金额:
    $ 93.94万
  • 项目类别:
Plasma Gelsolin and Host Defense After Lung Injury
肺损伤后血浆凝溶胶蛋白和宿主防御
  • 批准号:
    8446681
  • 财政年份:
    2013
  • 资助金额:
    $ 93.94万
  • 项目类别:
Plasma Gelsolin and Host Defense After Lung Injury
肺损伤后血浆凝溶胶蛋白和宿主防御
  • 批准号:
    8989922
  • 财政年份:
    2013
  • 资助金额:
    $ 93.94万
  • 项目类别:
Transgenerational Susceptibility to Asthma from Air Pollution Exposure
空气污染暴露对哮喘的跨代易感性
  • 批准号:
    8728858
  • 财政年份:
    2013
  • 资助金额:
    $ 93.94万
  • 项目类别:
RNAi Screen in Air Pollutant-Enhanced Influenza Infection
RNAi 筛查空气污染物增强型流感感染
  • 批准号:
    8272707
  • 财政年份:
    2011
  • 资助金额:
    $ 93.94万
  • 项目类别:
RNAi Screen in Air Pollutant-Enhanced Influenza Infection
RNAi 筛查空气污染物增强型流感感染
  • 批准号:
    8130454
  • 财政年份:
    2011
  • 资助金额:
    $ 93.94万
  • 项目类别:
Qiagen 96-Sample Pyrosequencer
Qiagen 96 样品焦磷酸测序仪
  • 批准号:
    7794497
  • 财政年份:
    2010
  • 资助金额:
    $ 93.94万
  • 项目类别:
Prenatal Programming of Neonatal Asthma Susceptibility
新生儿哮喘易感性的产前规划
  • 批准号:
    7750741
  • 财政年份:
    2009
  • 资助金额:
    $ 93.94万
  • 项目类别:

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