Hearing disorders pose significant challenges to individuals experiencing them and their overall quality of life, emphasizing the critical need for advanced pharmacological approaches to address these conditions. Current treatment options often focus on amplification devices, cochlear implants, or other rehabilitative therapies, leaving a substantial gap regarding effective pharmacological interventions. Advancements in our understanding of the molecular and cellular mechanisms involved in hearing disorders induced by noise, aging, and ototoxicity have opened new avenues for drug development, some of which have led to numerous clinical trials, with promising results. The development of optimal drug delivery solutions in animals and humans can also enhance the targeted delivery of medications to the ear. Moreover, large genome studies contributing to a genetic understanding of hearing loss in humans combined with advanced molecular technologies in animal studies have shown a great potential to increase our understanding of the etiologies of hearing loss. The auditory system exhibits circadian rhythms and temporal variations in its physiology, its vulnerability to auditory insults, and its responsiveness to drug treatments. The cochlear clock rhythms are under the control of the glucocorticoid system, and preclinical evidence suggests that the risk/benefit profile of hearing disorder treatments using chronopharmacological approaches would be beneficial. If translatable to the bedside, such approaches may improve the outcome of clinical trials. Ongoing research into the molecular and genetic basis of auditory disorders, coupled with advancements in drug formulation and delivery as well as optimized timing of drug administration, holds great promise of more effective treatments.

中文翻译：

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听力损失的药理学方法


听力障碍对患有听力障碍的个人及其整体生活质量构成了重大挑战，凸显了对先进药理学方法来解决这些疾病的迫切需求。目前的治疗选择通常集中在扩增装置、人工耳蜗或其他康复疗法上，在有效的药物干预方面留下了很大的差距。我们对噪音、衰老和耳毒性引起的听力障碍所涉及的分子和细胞机制的理解取得了进展，这为药物开发开辟了新的途径，其中一些导致了许多临床试验，并取得了可喜的结果。在动物和人类中开发最佳药物递送解决方案也可以增强药物向耳朵的靶向递送。此外，有助于人类听力损失遗传理解的大型基因组研究与动物研究中先进的分子技术相结合，显示出增加我们对听力损失病因的理解的巨大潜力。听觉系统在其生理机能中表现出昼夜节律和时间变化，它对听觉侮辱的脆弱性，以及它对药物治疗的反应性。耳蜗时钟节律受糖皮质激素系统的控制，临床前证据表明，使用时间药理学方法治疗听力障碍的风险/获益概况将是有益的。如果可转化为床边，这些方法可能会改善临床试验的结果。 对听觉障碍的分子和遗传基础的持续研究，加上药物配方和给药的进步以及给药时间的优化，为更有效的治疗带来了巨大的希望。