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，包括鼓膜造孔管，其提供通气并允许局部药物渗透鼓膜。已发现这种局部药物治疗非常有效。然而，手术是昂贵的，在世界上许多地方是不切实际的，导致听力损失和死亡，由于中耳炎在发展中国家。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顺序选择来鉴定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。我们建议扩展这项工作，确定所有确定的肽transstympanic运输的速率和饱和度。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鼓膜，并表征介导经鼓膜转运的结合伴侣。这项研究将为中耳疾病的治疗带来一种全新的模式。与全身药物相比，经鼓膜给药将实现更高的中耳药物水平，并避免副作用或脱靶效应。这种方法将广泛应用于中耳炎和其他中耳疾病的治疗。

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.