内耳治疗中的细胞外囊泡——病理生理学、生产制造及临床考量
Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.
作者信息
Warnecke Athanasia, Staecker Hinrich, Rohde Eva, Gimona Mario, Giesemann Anja, Szczepek Agnieszka J, Di Stadio Arianna, Hochmair Ingeborg, Lenarz Thomas
机构信息
Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany.
Cluster of Excellence of the German Research Foundation (DFG; "Deutsche Forschungsgemeinschaft") "Hearing4all", 30625 Hannover, Germany.
出版信息
J Clin Med. 2022 Dec 15;11(24):7455. doi: 10.3390/jcm11247455.
(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear.
(1) 背景:感音神经性听力损失是一种常见且使人衰弱的病症。迄今为止,尚无全面的药物干预措施。导致听力损失的复杂多样的分子病理学可能会限制我们使用小分子进行干预的能力。本综述聚焦于细胞外囊泡在耳科学中的应用潜力。(2) 方法:叙述性文献综述。(3) 结果:细胞外囊泡为调节广泛的病理和生理途径提供了机会,并且可以在药品生产质量管理规范(GMP)条件下制造,从而使其能够应用于人类内耳。展示了炎症在听力损失中的作用,重点是人工耳蜗植入。讨论了细胞外囊泡如何为内耳复杂的炎症性疾病提供治疗选择。此外,概述了将细胞外囊泡开发为用于内耳的高级治疗药品时需要解决的生产和监管问题。(4) 结论:鉴于内耳损伤的复杂性,细胞外囊泡等新型疗法可能提供一种调节内耳炎症、应激途径和细胞凋亡的方法。