New Treatment for Inflammation in Middle Ear Infections

描述（由申请人提供）：细菌感染是渗出性中耳炎（OME）的主要原因，OME是一种中耳炎性疾病。OME的特征在于中耳内促炎细胞因子的产生以及炎症和液体积聚的发展。虽然OME的主要治疗方法是抗生素，但没有直接针对炎症和液体积聚的治疗方法。该II期提案将提供治疗细菌诱导的炎症的疗法的临床前评估。靶向基因递送已经开发出一种新型肽药物，其特异性地阻断由细菌和免疫细胞的相互作用引起的细胞内信号传导和细胞活化（促炎细胞因子的产生）。初步的体内研究表明，在细菌诱导的OME的小鼠模型中具有显著的抗炎作用，中耳中的液体积聚、炎性细胞数量和粘膜增厚显著减少。在目前的研究中，实验将测试这种疗法在细菌诱导的OME小鼠模型中减少炎症的功效，以及这种新型疗法对改善听力阈值的影响。这些研究有可能确定一种治疗细菌诱导的炎症的新方法，该方法将应用于OME和各种其他炎症性疾病。

DESCRIPTION (provided by applicant): Bacterial infections are the primary cause of otitis media with effusion (OME), an inflammatory disease of the middle ear. OME is characterized by production of pro-inflammatory cytokines within the middle ear and development of inflammation and fluid accumulation. While the primary treatment for OME is antibiotics, there is no therapy that directly targets the inflammation and fluid accumulation. This Phase II proposal will provide pre-clinical assessment of a therapy to treat bacterial-induced inflammation. Targeted Gene Delivery has developed a novel peptide drug that specifically blocks the intracellular signaling and cell activation (production of pro-inflammatory cytokines) that results from the interaction of bacteria and immune cells. Preliminary in vivo studies demonstrated a significant anti-inflammatory effect in a mouse model of bacterial induced OME, with marked reduction in fluid accumulation, number of inflammatory cells, and mucosal thickening in the middle ear. In the current study, experiments will test the efficacy of this therapy in reducing inflammation in a mouse model of bacterial-induced OME and the impact of this novel therapy on improving hearing thresholds. These studies have the potential to define a new approach to treating bacterial-induced inflammation that will have application in OME and a variety of other inflammatory diseases.