Innovative therapy for diseases of the middle ear

描述（由申请人提供）：慢性中耳炎的治疗通常涉及手术，包括鼓膜造瘘管，其提供通气并允许局部药物通过鼓膜渗透。这种局部药物治疗已被发现是非常有效的。然而，手术费用昂贵，而且在世界上许多地方并不实际，导致发展中国家因中耳炎而导致听力损失和死亡。为了加强中耳疾病的医学治疗，我们使用噬菌体展示肽库的序列选择来识别在运输货物时主动穿过鼓膜的罕见的新型肽。初步数据表明，携带这些肽之一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鉴定肽的跨腹膜运输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。

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.