Intratympanic delivery of biologics for treatment of autoimmune inner ear disease

 感音神经性听力损失是一个主要的医疗问题，超过3200万美国人受到影响。最常见的形式是老年性耳聋或老年性听力损失。其他类型的听力损失包括噪音暴露，遗传损失，病毒和细菌感染，耳毒性药物，自身免疫性和特发性。对听力损失的分子生物学的理解正在继续发展。然而，许多常见临床病症的病理生理学仍不完全清楚。目前尚无FDA批准的用于治疗感音神经性听力损失的药物。该I期SBIR提案涉及制作感音神经性听力损失的治疗方法，特别关注自身免疫性内耳疾病。该提案的具体目标是为自身免疫性内耳疾病的圆窗给药治疗的生物制剂的早期开发提供路线图。该建议的目的有三个：首先，开发治疗制剂的原型延长释放组合物，以掺入所需的治疗剂量和释放持续时间。其次，将利用细胞培养分析来分析释放治疗剂的活性。第三，将在动物模型中测试缓释植入物制剂的安全性和药物在中耳和内耳中的分布。这将产生原型植入物，将释放活性治疗超过所需的四周时间。O-Ray的研究人员团队是唯一有资格执行本文提出的工作的团队，并且在耳科、药物开发和药物输送方面具有成功开发本产品的专业知识。O-Ray的科学家们已经成功地开发出了目前正在临床上使用的治疗配方。这包括眼内持续释放类固醇植入物，其能够从单次植入起维持抗炎性玻璃体内药物水平长达3年。该项目的第二阶段将涉及最终延长释放英夫利西单抗制剂的完成 用于生产规模扩大、这些制剂的稳定性和无菌性测试以及足以导致研究性新药豁免的安全性和药代动力学动物研究。这项工作的完成将最终促进与公司合作伙伴的合作，以获得我们开发产品的许可。

 DESCRIPTION (provided by applicant): Sensorineural hearing loss is a major medical problem with over 32 million Americans affected. The most common form is presbycusis or aging hearing loss. Other types of hearing loss include noise exposure, genetic losses, viral and bacterial infections, ototoxic medications, autoimmune, and idiopathic. The understanding of the molecular biology responsible for hearing loss is continuing to evolve. However, the pathophysiology of many common clinical conditions is still not completely understood. There is no FDA-approved pharmacological agent for treatment of sensorineural hearing loss. This Phase I SBIR proposal involves the fabrication of therapeutic treatments for sensorineural hearing loss, with a specific focus on autoimmune inner ear disease. The specific aims of this proposal present a roadmap towards the early stage development of biologic agent formulations for the round window administered treatment of autoimmune inner ear disease. The aims of this proposal are threefold: First, the development of prototype extended release composition of the therapeutic formulation to incorporate the desired therapeutic dose and release duration. Second, the activity of the release therapeutic will be analyzed utilizing cell culture analyses. Third, extended release implant formulations will be tested in animal models for safety and drug distribution in the middle and inner ear. This will yield prototype implants that will release actie therapeutic over the desired four week period. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, drug development and drug delivery for the successful development this product. O-Ray scientists have successfully developed therapeutic formulations that are currently being used in the clinic. This includes an intraocular sustained release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for periods of up to 3 years from a single implantation. Phase II of this project will involve completion of a final extended release infliximab formulation for a scale up in manufacture, the testing of stability and sterility of these formulations, and safety and pharmacokinetic animal studies sufficient to lead to an Investigational New Drug Exemption. The completion of this work will ultimately facilitate a collaboration with a corporate partner for the licensing of our developed product.