Brotto Davide, Greggio Marco, De Filippis Cosimo, Trevisi Patrizia
Department of Neuroscience DNS, Otolaryngology Section, Padova University, 35128 Padova, Italy.
Otolaryngology Unit, Azienda Ospedale Università Padova, 35128 Padova, Italy.
Audiol Res. 2024 Feb 22;14(2):239-253. doi: 10.3390/audiolres14020022.
The etiology of sensorineural hearing loss is heavily influenced by genetic mutations, with approximately 80% of cases attributed to genetic causes and only 20% to environmental factors. Over 100 non-syndromic deafness genes have been identified in humans thus far. In non-syndromic sensorineural hearing impairment, around 75-85% of cases follow an autosomal recessive inheritance pattern. In recent years, groundbreaking advancements in molecular gene therapy for inner-ear disorders have shown promising results. Experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome. These pioneering approaches have opened new possibilities for potential therapeutic interventions. Following the PRISMA criteria, we summarized the AAV gene therapy experiments showing hearing improvement in the preclinical phases of development in different animal models of DFNB deafness and the AAV gene therapy programs currently in clinical phases targeting autosomal recessive non syndromic hearing loss. A total of 17 preclinical studies and 3 clinical studies were found and listed. Despite the hurdles, there have been significant breakthroughs in the path of HL gene therapy, holding great potential for providing patients with novel and effective treatment.
感音神经性听力损失的病因受基因突变的影响很大，约80%的病例归因于遗传因素，只有20%归因于环境因素。迄今为止，人类已鉴定出100多种非综合征性耳聋基因。在非综合征性感音神经性听力障碍中，约75-85%的病例遵循常染色体隐性遗传模式。近年来，内耳疾病分子基因治疗取得了突破性进展，显示出了有前景的结果。实验研究表明，单次局部注射携带额外正常基因的腺相关病毒衍生载体或使用核酶修饰基因组后，听力有所改善。这些开创性方法为潜在的治疗干预开辟了新的可能性。按照PRISMA标准，我们总结了在不同DFNB耳聋动物模型临床前开发阶段显示听力改善的腺相关病毒基因治疗实验，以及目前针对常染色体隐性非综合征性听力损失的临床阶段腺相关病毒基因治疗项目。共找到并列出了17项临床前研究和3项临床研究。尽管存在障碍，但听力损失基因治疗道路上已取得重大突破，为为患者提供新颖有效的治疗方法具有巨大潜力。
