New Treatment for Inflammation in Middle Ear Infections

中耳感染炎症的新治疗方法

• 批准号: 7475777
• 负责人: SHARON L MCCOY
• 金额: $ 79.04万
• 依托单位: 13THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475777
• 关键词: Acute; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Bacteria; Cells; Clinical; Clinical Trials; Condition; Data; Disease; Dose; Gene Delivery; Gram-Negative Bacteria; Haemophilus influenzae; Hearing; Heating; Immune; Infection; Inflammation; Inflammatory; Investigational Drugs; Investigational New Drug Application; Lead; Modeling; Mus; Mutagenicity Tests; Otitis Media; Otitis Media with Effusion; Pain; Peptides; Phase; Phase II Clinical Trials; Purpose; Reporting; Severities; Signal Transduction; Streptococcus pneumoniae; Toxic effect; Toxicity Tests; United States Food and Drug Administration; Vaccinia virus; base; clinical efficacy; clinically relevant; ear infection; hearing impairment; improved; middle ear; middle ear disorder; novel strategies; novel therapeutics; pathogen; pre-clinical

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

描述（由申请人提供）：急性中耳炎（AOM）是中耳常见的炎症性疾病，其特征是疼痛和听力损失。抗生素治疗感染并经常导致症状缓解，但不能靶向诸如中耳积液（MEE）之类的炎症参数，这会导致听力损失和其他并发症。没有疗法直接靶向中耳炎症。靶向基因递送，Inc。已鉴定并表征了肽（肽P13），该肽会干扰细胞内促炎信号传导和细胞激活，这是由于病原体与免疫细胞的相互作用导致的。在第二阶段研究期间产生的数据表明，使用热灭活的肺炎链球菌和流感h。与肽治疗同时注射的鼠类模型中，中耳炎症显着减少。该II期竞争性更新建议的目的是产生临床前功效和毒性数据，以支持研究新药（IND）应用于使用肽P13作为AOM中的抗炎疗法。我们将使用生存的细菌和延迟的肽治疗在临床相关模型中检查肽P13的功效。这些研究完成后，我们将开始进行临床前毒性测试，以启动临床试验。这些研究有可能定义一种治疗中耳炎症的新方法，并将适用于感染导致有害炎症性疾病的其他临床状况。急性中耳炎（AOM）通常以延长的炎症为特征，导致听力损失和其他并发症。抗生素治疗感染，但不能靶向炎症。我们已经确定了一种新型的治疗肽，该肽在AOM的鼠模型中表现出显着的抗炎作用。通过疗效和毒性测试，该肽将作为治疗AOM的新疗法开发