NON-CLINICAL SAFETY ASSESSMENT OF ORC-13661 TO SUPPORT AMINOGLYCOSIDE INDUCED HEARING LOSS INDICATION. ADDITIONAL FUNDS.

氨基糖苷类抗生素（AG）是一类广谱抗生素，除用于治疗分枝杆菌疾病外，还用于治疗严重的需氧菌、革兰氏阴性菌感染。内耳毛细胞死亡引起的耳毒性是一种常见的不可逆的不良反应，限制了AG的使用。AG的耳毒性作用不仅限于听力损失，还影响前庭系统，导致头晕和平衡障碍。在许多患者中，平衡问题与听力缺陷一样明显和令人衰弱。临床前数据表明，ORC-13661（一种小分子）通过抑制AG通过机械电转导（MET）通道进入毛细胞，保护毛细胞免受AG的细胞毒性作用。本项目的目的是开发ORC-13661作为一种预防性治疗，以保护内耳听毛细胞免受AG治疗的不可逆毒副作用。

Aminoglycoside antibiotics (AGs) are a class of broad-spectrum antibiotics used to treat serious aerobic, gram-negative infections, in addition to mycobacterial diseases. Ototoxicity due to the death of inner ear hair cells is a common, irreversible adverse effect, limiting the use of AGs. The ototoxic effects of AGs are not limited to hearing loss, but also affect the vestibular system, causing dizziness and impairments to balance. In many patients the balance problems are as apparent and debilitating as hearing deficits. Preclinical data suggests that ORC-13661 (a small molecule) protects hair cells from the cytotoxic effects of AGs by inhibiting the entry of AGs into the hair cell through the mechanoelectrical transduction (MET) channel. The aim of this project is to develop ORC-13661 as an adjunctive therapy to protect inner ear auditory hair cells from the irreversible toxic side effects of AG treatment.