New Treatment for Inflammation in Middle Ear Infections

描述(申请人提供)：急性中耳炎(AOM)是一种常见的中耳炎症性疾病，以疼痛和听力丧失为特征。抗生素治疗感染，通常导致症状缓解，但不针对炎症参数，如中耳积液(MEE)，后者可能导致听力损失和其他并发症。没有直接针对中耳炎的治疗方法。靶向基因传递公司已经鉴定了一种多肽(多肽P13)，它可以干扰细胞内的促炎信号和细胞激活，这是病原体产品与免疫细胞相互作用的结果。在第二阶段研究期间产生的数据显示，在使用热灭活肺炎链球菌和流感嗜血杆菌同时注射多肽治疗的小鼠模型中，中耳炎症显著减少。这项第二阶段竞争性更新提案的目的将是产生临床前疗效和毒性数据，以支持研究新药(IND)应用，将P13肽用作AOM的抗炎疗法。我们将在一个临床相关的模型中使用活菌和延迟的多肽治疗来检查多肽P13的有效性。当这些研究完成后，我们将开始启动临床试验所需的临床前毒性测试。这些研究有可能确定一种治疗中耳炎的新方法，并将适用于感染导致有害炎症的其他临床情况。急性中耳炎(AOM)通常以长期炎症为特征，导致听力损失和其他并发症。抗生素治疗感染，但不针对炎症。我们已经确定了一种新的治疗多肽，在AOM的小鼠模型中显示了显著的抗炎作用。通过疗效和毒性试验，该多肽有望成为治疗AOM的新方法。

DESCRIPTION (provided by applicant): Acute otitis media (AOM) is a common inflammatory disease of the middle ear characterized by pain and hearing loss. Antibiotics treat infection and often result in symptomatic relief, but do not target inflammatory parameters such as middle ear effusion (MEE), which can cause hearing loss and other complications. No therapies directly target middle ear inflammation. Targeted Gene Delivery, Inc. has identified and characterized a peptide (peptide P13) that interferes with intracellular pro-inflammatory signaling and cell activation that results from the interaction of pathogen products with immune cells. Data generated during the Phase II study demonstrated a dramatic reduction in middle ear inflammation in a murine model using heat- inactivated S. pneumoniae and H. influenzae injected simultaneously with peptide treatment. The purpose of this Phase II Competing Renewal proposal will be to generate pre-clinical efficacy and toxicity data to support an Investigational New Drug (IND) application to use peptide P13 as an anti-inflammatory therapy in AOM. We will examine peptide P13 efficacy in a clinically relevant model using viable bacteria and delayed peptide treatment. When these studies are completed, we will begin the pre-clinical toxicity testing necessary to initiate clinical trials. These studies have the potential to define a new approach to treating middle ear inflammation and will have application for other clinical conditions in which infections lead to detrimental inflammatory disease. Acute otitis media (AOM) is often characterized by prolonged inflammation that causes hearing loss and other complications. Antibiotics treat infection, but do not target inflammation. We have identified a novel therapeutic peptide that has demonstrated significant anti-inflammatory effects in a murine model of AOM. Through efficacy and toxicity testing, this peptide will be developed as a new therapy for treatment of AOM