Innovative therapy for diseases of the middle ear

中耳疾病的创新疗法

• 批准号: 8860171
• 负责人: Allen F. Ryan
• 金额: $ 32.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8860171
• 关键词: Adenoidal structure; Adverse effects; Age; Antibiotics; Bacteria; Bacteriophages; Basic Science; Binding; Biological; Cessation of life; Child; Chronic; Clinical; Clinical Trials; Data; Disadvantaged; Drug Delivery Systems; Drug Transport; Ear Diseases; Ensure; Excision; Exposure to; External Ear; Family; Health; Human; Innovative Therapy; Lead; Libraries; Ligands; Mediating; Medical; Membrane; Methodology; Mining; Molecular; Operative Surgical Procedures; Otitis Media; Patient observation; Penetration; Peptide Library; Peptide Phage Display Library; Peptides; Phage Display; Pharmaceutical Preparations; Property; Research; Research Project Grants; Side; Techniques; Time; Translating; Translational Research; Treatment Cost; Treatment Failure; Tube; Tympanic membrane; Tympanostomy; Tympanostomy Tube Insertions; Work; active method; combinatorial; dosage; drug development; drug discovery; ear infection; hearing impairment; improved; innovation; middle ear; middle ear disorder; novel; novel therapeutics; particle; programs; receptor; screening

DESCRIPTION (provided by applicant): Treatment for chronic otitis media often involves surgery, including tympanostomy tubes which provide aeration and allow the penetration of topical medications through the tympanic membrane. Such local drug treatment has been found to be highly effective. However, surgery is expensive and in many parts of the world is not practical, leading to hearing loss and deaths due to otitis media in the developing world. To enhance medical treatment of middle ear disorders, we used sequential selection of phage-display peptide libraries to identify rare, novel peptides that actively cross the tympanic membrane while transporting cargo. Preliminary data indicate that a bacteriophage bearing one of these peptides enters the middle ear at 106 times the rate of an untargeted phage. We propose to extend this work by determining the rate and saturation level of transtympanic transport for all identified peptides. We will evaluate the external ear, tympanic membrane and middle ear after transtympanic peptide exposure, to determine whether there are any adverse effects, and assess the ability of peptides to carry drugs and to influence a middle ear infection. We will also determine whether these peptides cross the human tympanic membrane, and characterize the binding partners that mediate transtympanic transport. The proposed research will lead to an entirely novel paradigm for the treatment of middle ear diseases. Transtympanic drug delivery would achieve higher middle ear drug levels and avoid side- or off-target effects, when compared to systemic medications. This methodology will have widespread applications for the treatment of otitis media and other middle ear conditions.

描述（由申请人提供）：慢性中耳炎的治疗通常涉及手术，包括提供通气并允许局部药物渗透鼓膜的鼓膜造口管。已发现这种局部药物治疗非常有效。然而，手术费用昂贵，而且在世界许多地方并不实用，导致发展中国家因中耳炎而导致听力损失和死亡。为了加强对中耳疾病的治疗，我们使用噬菌体展示肽库的顺序选择来识别在运输货物时主动穿过鼓膜的稀有的新型肽。初步数据表明，携带其中一种肽的噬菌体进入中耳的速度是非靶向噬菌体的 106 倍。我们建议通过确定所有已识别肽的跨鼓膜运输的速率和饱和水平来扩展这项工作。我们将评估经鼓膜肽暴露后的外耳、鼓膜和中耳，以确定是否有任何不良反应，并评估肽携带药物和影响中耳感染的能力。 我们还将确定这些肽是否穿过人类鼓膜，并表征介导跨鼓膜转运的结合伙伴。拟议的研究将为治疗中耳疾病带来全新的范例。与全身药物治疗相比，经鼓室药物输送将达到更高的中耳药物水平，并避免副作用或脱靶效应。该方法将广泛应用于治疗中耳炎和其他中耳疾病。