Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness
https://orcid.org/0000-0002-3885-543X
AbstractMutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno‐associated virus (AAV)‐mediated OTOF gene replacement therapy is extensively validated in Otof‐deficient mice. However, the clinical safety and efficacy of AAV‐OTOF is not reported. Here, AAV‐OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non‐human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV‐OTOF is delivered into one cochlea of a 5‐year‐old deaf patient and into the bilateral cochleae of an 8‐year‐old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure‐tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5‐year‐old patient can be restored to the normal range at 1 month after AAV‐OTOF injection, while the 8‐year‐old patient can hear the conversational sounds. Most importantly, the 5‐year‐old patient can hear and recognize speech only through the AAV‐OTOF‐injected ear. This study is the first to demonstrate the safety and efficacy of AAV‐OTOF in patients, expands and optimizes current OTOF‐related gene therapy and provides valuable information for further application of gene therapies for deafness.
AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness
https://orcid.org/0000-0002-3885-543X
AbstractMutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno‐associated virus (AAV)‐mediated OTOF gene replacement therapy is extensively validated in Otof‐deficient mice. However, the clinical safety and efficacy of AAV‐OTOF is not reported. Here, AAV‐OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non‐human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV‐OTOF is delivered into one cochlea of a 5‐year‐old deaf patient and into the bilateral cochleae of an 8‐year‐old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure‐tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5‐year‐old patient can be restored to the normal range at 1 month after AAV‐OTOF injection, while the 8‐year‐old patient can hear the conversational sounds. Most importantly, the 5‐year‐old patient can hear and recognize speech only through the AAV‐OTOF‐injected ear. This study is the first to demonstrate the safety and efficacy of AAV‐OTOF in patients, expands and optimizes current OTOF‐related gene therapy and provides valuable information for further application of gene therapies for deafness.
AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness
https://orcid.org/0000-0002-3885-543X
AbstractMutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno‐associated virus (AAV)‐mediated OTOF gene replacement therapy is extensively validated in Otof‐deficient mice. However, the clinical safety and efficacy of AAV‐OTOF is not reported. Here, AAV‐OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non‐human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV‐OTOF is delivered into one cochlea of a 5‐year‐old deaf patient and into the bilateral cochleae of an 8‐year‐old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure‐tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5‐year‐old patient can be restored to the normal range at 1 month after AAV‐OTOF injection, while the 8‐year‐old patient can hear the conversational sounds. Most importantly, the 5‐year‐old patient can hear and recognize speech only through the AAV‐OTOF‐injected ear. This study is the first to demonstrate the safety and efficacy of AAV‐OTOF in patients, expands and optimizes current OTOF‐related gene therapy and provides valuable information for further application of gene therapies for deafness.
AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness
Advanced Science
Qi, Jieyu (Autor:in) / Tan, Fangzhi (Autor:in) / Zhang, Liyan (Autor:in) / Lu, Ling (Autor:in) / Zhang, Shanzhong (Autor:in) / Zhai, Yabo (Autor:in) / Lu, Yicheng (Autor:in) / Qian, Xiaoyun (Autor:in) / Dong, WenXiu (Autor:in) / Zhou, Yinyi (Autor:in)
Advanced Science ; 11
01.03.2024
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness
| Wiley | 2024
AAV‐mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives
| Wiley | 2024
Preclinical Efficacy And Safety Evaluation of AAV‐OTOF in DFNB9 Mouse Model And Nonhuman Primate
| Wiley | 2024
Screening for mutations in the GJB3 gene in Brazilian patients with nonsyndromic deafness
| British Library Online Contents | 2004
Craniofacial-Deafness-Hand Syndrome Revisited
| British Library Conference Proceedings | 2003