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Plasma Gelsolin as Immunotherapeutic for Antibiotic-Resistant Pneumonia

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

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英文摘要
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.
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Plasma Gelsolin as Immunotherapeutic for Antibiotic-Resistant Pneumonia
  • 批准号:
    9275351
  • 项目类别:
  • 资助金额:
    $97.08万
  • 财政年份:
    2016
  • 负责人:
    LESTER KOBZIK
  • 依托单位:
2014 Biology of Acute Respiratory Infection Gordon Research Conference and Semina
  • 批准号:
    8650427
  • 项目类别:
  • 资助金额:
    $0.7万
  • 财政年份:
    2014
  • 负责人:
    LESTER KOBZIK
  • 依托单位:
Transgenerational Susceptibility to Asthma from Air Pollution Exposure
  • 批准号:
    8598612
  • 项目类别:
  • 资助金额:
    $28.26万
  • 财政年份:
    2013
  • 负责人:
    LESTER KOBZIK
  • 依托单位:
Plasma Gelsolin and Host Defense After Lung Injury
  • 批准号:
    8446681
  • 项目类别:
  • 资助金额:
    $40.38万
  • 财政年份:
    2013
  • 负责人:
    LESTER KOBZIK
  • 依托单位:
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