Emerging Therapies for Sensorineural Hearing Loss
Emerging Therapies for Sensorineural Hearing Loss
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DOI：
10.1097/mao.0000000000001427
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发表时间：
2017-07-01
影响因子：
2.1
通讯作者：
Tucci, Debara L.
中科院分区：
文献类型：
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作者：
Crowson, Matthew Gordon;Hertzano, Ronna;Tucci, Debara L.
目的：严格审查和评估目前正在进行的治疗感音神经性听力损失的临床药物试验的拟议机制和记录结果。数据来源：美国国立卫生研究院（NIH）临床试验登记处，MEDLINE/PubMed。研究选择和数据提取：对NIH临床试验登记处的审查确定了候选听力损失疗法，并从MEDLINE/PubMed获得了支持性出版物。对概念验证、治疗机制和临床结果进行了严格的评估。数据综合：确定了在美国注册的22个活跃的临床药物试验，并对6个潜在的治疗分子进行了审查。在审查的六种分子中，有四种分子包含与减轻氧化应激途径有关的机制，这些途径可能导致内耳细胞死亡。剩下的一种疗法试图操纵细胞死亡级联，最后剩下的疗法是一种新的细胞替代疗法的方法，引入一种转录因子，促进毛细胞regeneration.Conclusion：一个共同的主题，最近在美国注册的临床试验似乎是靶向细胞死亡途径和氧化应激对耳蜗感觉神经上皮细胞的影响。此外，病毒递送的细胞替代疗法将是第一种此类疗法，如果它被证明是安全有效的。将这些从工作台到床边的疗法推向市场的重大挑战仍然存在。在非人类动物模型中的结果永远不能保证在人类生物学背景下转化为有效的疗法。此外，由于描述了与听力损失相关的其他过程，例如免疫反应和突触接触的丧失，因此可以使用其他靶向途径。
Objective: To critically review and evaluate the proposed mechanisms and documented results of the therapeutics currently in active clinical drug trials for the treatment of sensorineural hearing loss.Data Sources: US National Institutes of Health (NIH) Clinical Trials registry, MEDLINE/PubMed.Study Selection & Data Extraction: A review of the NIH Clinical Trials registry identified candidate hearing loss therapies, and supporting publications were acquired from MEDLINE/PubMed. Proof-of-concept, therapeutic mechanisms, and clinical outcomes were critically appraised.Data Synthesis: Twenty-two active clinical drug trials registered in the United States were identified, and six potentially therapeutic molecules were reviewed. Of the six molecules reviewed, four comprised mechanisms pertaining to mitigating oxidative stress pathways that presumably lead to inner ear cell death. One remaining therapy sought to manipulate the cell death cascade, and the last remaining therapy was a novel cell replacement therapy approach to introduce a transcription factor that promotes hair cell regeneration.Conclusion: A common theme in recent clinical trials registered in the United States appears to be the targeting of cell death pathways and influence of oxidant stressors on cochlear sensory neuroepithelium. In addition, a virus-delivered cell replacement therapy would be the first of its kind should it prove safe and efficacious. Significant challenges for bringing these bench-to-bedside therapies to market remain. It is never assured that results in non-human animal models translate to effective therapies in the setting of human biology. Moreover, as additional processes are described in association with hearing loss, such as an immune response and loss of synaptic contacts, additional pathways for targeting become available.