Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Human Genetics and John P. Hussman Institute of Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL, USA.
Gene. 2020 Jul 15;747:144677. doi: 10.1016/j.gene.2020.144677. Epub 2020 Apr 15.
The progressive, late-onset, nonsyndromic, sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment globally, with presbycusis affecting greater than a third of individuals over the age of 65. The etiology underlying PNSHL include presbycusis, noise-induced hearing loss, drug ototoxicity, and delayed-onset autosomal dominant hearing loss (AD PNSHL). The objective of this article is to discuss the potential diagnostic and therapeutic applications of genomic medicine in PNSHL. Genomic factors contribute greatly to PNSHL. The heritability of presbycusis ranges from 25 to 75%. Current therapies for PNSHL range from sound amplification to cochlear implantation (CI). PNSHL is an excellent candidate for genomic medicine approaches as it is common, has well-described pathophysiology, has a wide time window for treatment, and is amenable to local gene therapy by currently utilized procedural approaches. AD PNSHL is especially suited to genomic medicine approaches that can disrupt the expression of an aberrant protein product. Gene therapy is emerging as a potential therapeutic strategy for the treatment of PNSHL. Viral gene delivery approaches have demonstrated promising results in human clinical trials for two inherited causes of blindness and are being used for PNSHL in animal models and a human trial. Non-viral gene therapy approaches are useful in situations where a transient biologic effect is needed or for delivery of genome editing reagents (such as CRISPR/Cas9) into the inner ear. Many gene therapy modalities that have proven efficacious in animal trials have potential to delay or prevent PNSHL in humans. The development of new treatment modalities for PNSHL will lead to improved quality of life of many affected individuals and their families.
进行性、迟发性、非综合征性、感觉神经性听力损失（PNSHL）是全球最常见的感觉功能障碍原因，年龄超过 65 岁的人群中有超过三分之一受到老年性聋的影响。PNSHL 的病因包括老年性聋、噪声性听力损失、药物耳毒性和迟发性常染色体显性遗传性听力损失（AD PNSHL）。本文的目的是讨论基因组医学在 PNSHL 中的潜在诊断和治疗应用。基因组因素对 PNSHL 有很大的影响。老年性聋的遗传率范围为 25%至 75%。目前 PNSHL 的治疗方法包括声音放大到人工耳蜗植入（CI）。PNSHL 是基因组医学方法的一个很好的候选者，因为它很常见，具有明确的病理生理学，有广泛的治疗时间窗口，并且可以通过目前使用的程序方法进行局部基因治疗。AD PNSHL 特别适合采用基因组医学方法来干扰异常蛋白产物的表达。基因治疗正在成为治疗 PNSHL 的一种潜在治疗策略。病毒基因传递方法在人类临床试验中已证明对两种遗传性失明原因有效，并且正在动物模型和人类临床试验中用于 PNSHL。非病毒基因治疗方法在需要短暂生物学效应或用于将基因组编辑试剂（如 CRISPR/Cas9）递送到内耳的情况下很有用。许多已在动物试验中证明有效的基因治疗模式有可能延缓或预防人类 PNSHL。PNSHL 新治疗模式的发展将提高许多受影响个体及其家庭的生活质量。
