Improving the Performance of Cochlear Implants for DFNB8/10 by accompanying Gene Therapy

在重度听力损失的情况下，人工耳蜗植入（CI）可以将听力恢复到大多数人可以在日常生活中理解语言的水平。脑前皮层上的电极电刺激并因此激活了螺旋神经节神经元（SGN），这是听觉通路的第一个神经元。因此，完整的SGN和功能正常的听觉通路对于良好的CI表现是绝对必要的。在基因TMPRSS3突变的情况下，导致隐性遗传性听力损失DFNB8/10，电刺激引起较低的SGN反应。儿童期人工耳蜗植入可获得良好的CI听力，但成人的结果差异很大。这与在小鼠模型中观察到的SGN细胞体急剧减少的观察结果一致。我的研究项目旨在破解导致DFNB8/10的TMPRSS3基因突变患者CIs表现变化和下降的原因。随后，我的目标是开发一种基因疗法来改善这种形式的听力损失的动物模型中的CI性能。

In cases of profound hearing loss, cochlear implantation (CI) can restore hearing to a level where most people can understand speech in everyday life. Electrodes on the CI electrically stimulate and thus activate spiral ganglion neurons (SGN), the first neurons of the auditory pathway. Therefore, intact SGN and a functioning auditory pathway are absolutely necessary for good CI performance. In the case of mutations in the gene TMPRSS3, which cause the recessively inherited hearing loss DFNB8/10, electrical stimulation evokes lower SGN responses. Cochlear implantation in childhood resulted in good hearing with CI, but the outcome in adults was highly variable. This is in line with the observation that a drastic reduction in SGN cell bodies was observed in the mouse model. My research project aims at deciphering the reason why CIs performance varies and declines in patients with mutations in the TMPRSS3 gene causing DFNB8/10. Subsequently, I aim to develop a gene therapy to improve CI performance in animal models for this form of hearing loss.