Sci Trans Med:腺相关病毒治疗聋鼠听觉

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美国科学家以病毒修复失聪老鼠的基因，使其恢复部分听力，可望为治疗先天失聪带来突破。

据香港《明报》先天失聪个案近半与基因缺陷有关，涉及逾70种不同的基因。其中耳朵内用于将声音转化为电子信号、传送至大脑分析的毛细胞，或因一种名为TMC1的基因出现缺陷而令人“听不见“声音。

美国波士顿儿童医院集中研究TMC1缺陷，以TMC1出现问题而严重失聪的老鼠做实验。这些老鼠连115分贝左右的声音（约等同摇滚音乐会的声浪）亦听不见。研究人员利用腺相关病毒感染其毛细胞，使其表达外源TMC1，以修复听觉出现缺陷的毛细胞。结果在1个月内，受感染老鼠听力显著改善，听到85分贝的声音（约等同汽车行驶的声浪）时有跳起等反应，并出现相应的听觉脑电波；未受感染的老鼠则没有变化。

参与研究的医学专家霍尔特（Jeffrey Holt）称需作进一步研究，确认治疗效果的持久度，相信不久将来可发展出针对基因致聋的疗法。研究报告刊于《科学转化医学》期刊。

来源：参考消息网

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Tmc gene therapy restores auditory function in deaf mice

Charles Askew1,2, Cylia Rochat3, Bifeng Pan1, Yukako Asai1, Hena Ahmed1, Erin Child1, Bernard L. Schneider3, Patrick Aebischer3 and Jeffrey R. Holt1,*

Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel–like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken β-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations.

http://stm.sciencemag.org/content/7/295/295ra108