Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success.
Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success.
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DOI：
10.3389/fnmol.2018.00221
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发表时间：
2018
影响因子：
4.8
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Zhang W;Kim SM;Wang W;Cai C;Feng Y;Kong W;Lin X
感音神经性听力损失（SNHL）影响着数百万人。基因突变在先天性和晚发性SNHL（如年龄依赖性听力损失，ADHL）中都起着重要而直接的作用。虽然助听器可以帮助中度至重度听力损失，但对耳聋患者唯一有效的治疗方法是人工耳蜗（CI）。基因和细胞疗法可能保留或恢复听力，更自然的声音感知，因为它们的理论频率分辨率比人工耳蜗高得多。这些基于生物的干预措施也有可能在不需要植入任何假体装置的情况下重建听力；这种基于生物学的干预所提供的便利和较低的经济负担可能会使更多的SNHL患者受益。近年来，耳蜗基因治疗的临床前研究取得了重大进展。这篇综述批判性地评估了SNHL基因治疗临床前试验的最新进展，以及这种新疗法发展和最终临床转化的主要挑战。耳蜗与基因治疗转译研究的眼睛有许多相似之处。在眼部基因治疗试验中获得的经验，其中许多已进入临床三期，可能为提高耳蜗基因治疗在人体试验中成功的机会提供有价值的指导。因此，本文将讨论从大量先进的眼科基因治疗临床试验中收集到的转化知识的潜在意义。
Sensorineural hearing loss (SNHL) affects millions of people. Genetic mutations play a large and direct role in both congenital and late-onset cases of SNHL (e.g., age-dependent hearing loss, ADHL). Although hearing aids can help moderate to severe hearing loss the only effective treatment for deaf patients is the cochlear implant (CI). Gene- and cell-based therapies potentially may preserve or restore hearing with more natural sound perception, since their theoretical frequency resolution power is much higher than that of cochlear implants. These biologically-based interventions also carry the potential to re-establish hearing without the need for implanting any prosthetic device; the convenience and lower financial burden afforded by such biologically-based interventions could potentially benefit far more SNHL patients. Recently major progress has been achieved in preclinical studies of cochlear gene therapy. This review critically evaluates recent advances in the preclinical trials of gene therapies for SNHL and the major remaining challenges for the development and eventual clinical translation of this novel therapy. The cochlea bears many similarities to the eye for translational studies of gene therapies. Experience gained in ocular gene therapy trials, many of which have advanced to clinical phase III, may provide valuable guidance in improving the chance of success for cochlear gene therapy in human trials. A discussion on potential implications of translational knowledge gleaned from large numbers of advanced clinical trials of ocular gene therapy is therefore included.
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影响因子：
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