International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials

Xintai Fan; Ziwen Gao; Jiake Zhong; Yuxin Chen; Xiaoyun Chen; Lukas D. Landegger; Tobias Moser; Fan Gang Zeng; Yu Sun; Xin Jin; Robert Nash; Wade W. Chien; Dan Jiang; John H. Greinwald; Manohar Bance; Manuel Manrique Rodríguez; Sang Yeon Lee; Guodong Feng; Haidi Yang; Chen Chi Wu; Lei Xu; Wei Yuan; Yong Feng; Yu Zhao; Barbara Vona; Nicola Strenzke; Dirk Beutner; Nikul Amin; James Arwyn-Jones; Deepak Chandrasekeharan; Dazhi Shi; Di Zhang; Jianming Yang; Jieyu Qi; Qin Wang; Yanbo Yin; Yen Fu Cheng; Yong Tao; Yongfu Yu; Daqi Wang; Luoying Jiang; Luo Guo; Liheng Chen; Xiaoting Cheng; Chong Cui; Jun Lv; Shuang Han; Wuqing Wang; Yongxin Li; Xia Gao; Xue Zhong Liu; Dingjun Zha; Haibo Shi; Bing Chen; Qiuju Wang; Huijun Yuan; Shiming Yang; Shankai Yin; Hao Wu; Zhengmin Wang; Huawei Li; Jay T. Rubinstein; Lawrence R. Lustig; Renjie Chai; Zheng Yi Chen; Yilai Shu

doi:10.1016/j.medj.2025.100886

International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials

Xintai Fan
, Ziwen Gao
, Jiake Zhong
, Yuxin Chen
, Xiaoyun Chen
, Lukas D. Landegger
, Tobias Moser
, Fan Gang Zeng
, Yu Sun
, Xin Jin
, Robert Nash
, Wade W. Chien
, Dan Jiang
, John H. Greinwald
, Manohar Bance
, Manuel Manrique Rodríguez
, Sang Yeon Lee
, Guodong Feng
, Haidi Yang
, Chen Chi Wu

Lei Xu, Wei Yuan, Yong Feng, Yu Zhao, Barbara Vona, Nicola Strenzke, Dirk Beutner, Nikul Amin, James Arwyn-Jones, Deepak Chandrasekeharan, Dazhi Shi, Di Zhang, Jianming Yang, Jieyu Qi, Qin Wang, Yanbo Yin, Yen Fu Cheng, Yong Tao, Yongfu Yu, Daqi Wang, Luoying Jiang, Luo Guo, Liheng Chen, Xiaoting Cheng, Chong Cui, Jun Lv, Shuang Han, Wuqing Wang, Yongxin Li, Xia Gao, Xue Zhong Liu, Dingjun Zha, Haibo Shi, Bing Chen, Qiuju Wang, Huijun Yuan, Shiming Yang, Shankai Yin, Hao Wu, Zhengmin Wang, Huawei Li, Jay T. Rubinstein, Lawrence R. Lustig^*, Renjie Chai^*, Zheng Yi Chen^*, Yilai Shu^*

^*Corresponding author for this work

School of Life Science

Department of Otorhinolaryngology and ENT Institute
Fudan University
Key Laboratory of Hearing Medicine of NHFPC
State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science
Institutes of Biomedical Sciences
Department of Otolaryngology – Head and Neck Surgery
Stanford University
Department of Otolaryngology-Head and Neck Surgery
Medical University of Vienna
Institute for Auditory Neuroscience and InnerEarLab
University of Göttingen
Department of Otolaryngology
Auditory Neuroscience and Synaptic Nanophysiology Group
Max Planck Institute for Multidisciplinary Sciences
Center for Hearing Research
University of California at Irvine
Department of Otorhinolaryngology
Huazhong University of Science and Technology
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Department of Paediatric Otolaryngology
Great Ormond Street Hospital for Children NHS Foundation Trust
University College London
Department of Otolaryngology-Head and Neck Surgery
Johns Hopkins University
Hearing Implant Centre
Guy's and St. Thomas’ NHS Foundation Trust
King's College London
Division of Otolaryngology
University of Cincinnati
University of Cambridge
Departamento de Otorrinolaringología
University of Navarra
Department of Otorhinolaryngology-Head and Neck Surgery
Seoul National University
Department of Otorhinolaryngology
Chinese Academy of Medical Sciences
Department of Otolaryngology
Sun Yat-Sen University
Department of Otolaryngology
Taiwan University Hospital
Department of Otolaryngology-Head and Neck Surgery
Shandong University
Department of Otolaryngology
Chongqing General Hospital
Department of Otorhinolaryngology
University of South China
Department of Otolaryngology Head and Neck Surgery
Sichuan University
Institute for Auditory Neuroscience and InnerEarLab
Department of Otolaryngology
Second Hospital Affiliated to Southern University of Science and Technology
Department of Otolaryngology-Head and Neck Surgery
Anhui Medical University
Beijing Institute of Technology
Beijing Institute of Technology (Zhuhai)
Department of Otolaryngology – Head and Neck Surgery
Central South University
Department of Otolaryngology-Head and Neck Surgery
Veterans General Hospital-Taipei
Institute of Brain Science
Yang Ming Chiao Tung University
Department of Otolaryngology-Head and Neck Surgery
Shanghai Jiao Tong University
Ear Institute
Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases
Department of Otorhinolaryngology
Capital Medical University
Department of Otolaryngology Head and Neck Surgery
Nanjing University
University of Miami
Department of Otolaryngology Head and Neck Surgery
Air Force Medical University
Department of Otorhinolaryngology Head and Neck Surgery
Senior Department of Otolaryngology Head and Neck Surgery
General Hospital of People's Liberation Army
Institute of Rare Diseases
PLA General Hospital
Key Laboratory of Hearing Science
Ministry of Education in China
Beijing Key Laboratory of Hearing Impairment Prevention and Treatment
University of Washington
Department of Otolaryngology - Head and Neck Surgery
Columbia University
Southeast University, Nanjing
Nantong University
University of Electronic Science and Technology of China
Southeast University Shenzhen Research Institute
Eaton-Peabody Laboratories
Massachusetts Eye and Ear

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Background: Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss. Methods: A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75% agreement for inclusion. Findings: From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement). Conclusions: This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms. Funding: This work was supported by the National Natural Science Foundation of China, the German Research Foundation (DFG) via the Cluster of Excellence, and others.

Original language	English
Article number	100886
Journal	Med
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.medj.2025.100886
Publication status	Published - 9 Jan 2026

Keywords

Translation to population health
adeno-associated virus
clinical trial
expert consensus
gene therapy
hereditary hearing loss
modified Delphi method

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10.1016/j.medj.2025.100886

Cite this

Fan, X., Gao, Z., Zhong, J., Chen, Y., Chen, X., Landegger, L. D., Moser, T., Zeng, F. G., Sun, Y., Jin, X., Nash, R., Chien, W. W., Jiang, D., Greinwald, J. H., Bance, M., Rodríguez, M. M., Lee, S. Y., Feng, G., Yang, H., ... Shu, Y. (2026). International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials. Med, 7(1), Article 100886. https://doi.org/10.1016/j.medj.2025.100886

@article{05aa835d211f4677a4f423aa0baa8b82,

title = "International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials",

abstract = "Background: Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss. Methods: A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75\% agreement for inclusion. Findings: From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement). Conclusions: This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms. Funding: This work was supported by the National Natural Science Foundation of China, the German Research Foundation (DFG) via the Cluster of Excellence, and others.",

keywords = "Translation to population health, adeno-associated virus, clinical trial, expert consensus, gene therapy, hereditary hearing loss, modified Delphi method",

author = "Xintai Fan and Ziwen Gao and Jiake Zhong and Yuxin Chen and Xiaoyun Chen and Landegger, \{Lukas D.\} and Tobias Moser and Zeng, \{Fan Gang\} and Yu Sun and Xin Jin and Robert Nash and Chien, \{Wade W.\} and Dan Jiang and Greinwald, \{John H.\} and Manohar Bance and Rodr{\'i}guez, \{Manuel Manrique\} and Lee, \{Sang Yeon\} and Guodong Feng and Haidi Yang and Wu, \{Chen Chi\} and Lei Xu and Wei Yuan and Yong Feng and Yu Zhao and Barbara Vona and Nicola Strenzke and Dirk Beutner and Nikul Amin and James Arwyn-Jones and Deepak Chandrasekeharan and Dazhi Shi and Di Zhang and Jianming Yang and Jieyu Qi and Qin Wang and Yanbo Yin and Cheng, \{Yen Fu\} and Yong Tao and Yongfu Yu and Daqi Wang and Luoying Jiang and Luo Guo and Liheng Chen and Xiaoting Cheng and Chong Cui and Jun Lv and Shuang Han and Wuqing Wang and Yongxin Li and Xia Gao and Liu, \{Xue Zhong\} and Dingjun Zha and Haibo Shi and Bing Chen and Qiuju Wang and Huijun Yuan and Shiming Yang and Shankai Yin and Hao Wu and Zhengmin Wang and Huawei Li and Rubinstein, \{Jay T.\} and Lustig, \{Lawrence R.\} and Renjie Chai and Chen, \{Zheng Yi\} and Yilai Shu",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2026",

month = jan,

day = "9",

doi = "10.1016/j.medj.2025.100886",

language = "English",

volume = "7",

journal = "Med",

issn = "2666-6359",

publisher = "Cell Press",

number = "1",

}

Fan, X, Gao, Z, Zhong, J, Chen, Y, Chen, X, Landegger, LD, Moser, T, Zeng, FG, Sun, Y, Jin, X, Nash, R, Chien, WW, Jiang, D, Greinwald, JH, Bance, M, Rodríguez, MM, Lee, SY, Feng, G, Yang, H, Wu, CC, Xu, L, Yuan, W, Feng, Y, Zhao, Y, Vona, B, Strenzke, N, Beutner, D, Amin, N, Arwyn-Jones, J, Chandrasekeharan, D, Shi, D, Zhang, D, Yang, J, Qi, J, Wang, Q, Yin, Y, Cheng, YF, Tao, Y, Yu, Y, Wang, D, Jiang, L, Guo, L, Chen, L, Cheng, X, Cui, C, Lv, J, Han, S, Wang, W, Li, Y, Gao, X, Liu, XZ, Zha, D, Shi, H, Chen, B, Wang, Q, Yuan, H, Yang, S, Yin, S, Wu, H, Wang, Z, Li, H, Rubinstein, JT, Lustig, LR, Chai, R, Chen, ZY & Shu, Y 2026, 'International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials', Med, vol. 7, no. 1, 100886. https://doi.org/10.1016/j.medj.2025.100886

TY - JOUR

T1 - International expert consensus on gene therapy for hereditary hearing loss

T2 - Based on clinical trials

AU - Fan, Xintai

AU - Gao, Ziwen

AU - Zhong, Jiake

AU - Chen, Yuxin

AU - Chen, Xiaoyun

AU - Landegger, Lukas D.

AU - Moser, Tobias

AU - Zeng, Fan Gang

AU - Sun, Yu

AU - Jin, Xin

AU - Nash, Robert

AU - Chien, Wade W.

AU - Jiang, Dan

AU - Greinwald, John H.

AU - Bance, Manohar

AU - Rodríguez, Manuel Manrique

AU - Lee, Sang Yeon

AU - Feng, Guodong

AU - Yang, Haidi

AU - Wu, Chen Chi

AU - Xu, Lei

AU - Yuan, Wei

AU - Feng, Yong

AU - Zhao, Yu

AU - Vona, Barbara

AU - Strenzke, Nicola

AU - Beutner, Dirk

AU - Amin, Nikul

AU - Arwyn-Jones, James

AU - Chandrasekeharan, Deepak

AU - Shi, Dazhi

AU - Zhang, Di

AU - Yang, Jianming

AU - Qi, Jieyu

AU - Wang, Qin

AU - Yin, Yanbo

AU - Cheng, Yen Fu

AU - Tao, Yong

AU - Yu, Yongfu

AU - Wang, Daqi

AU - Jiang, Luoying

AU - Guo, Luo

AU - Chen, Liheng

AU - Cheng, Xiaoting

AU - Cui, Chong

AU - Lv, Jun

AU - Han, Shuang

AU - Wang, Wuqing

AU - Li, Yongxin

AU - Gao, Xia

AU - Liu, Xue Zhong

AU - Zha, Dingjun

AU - Shi, Haibo

AU - Chen, Bing

AU - Wang, Qiuju

AU - Yuan, Huijun

AU - Yang, Shiming

AU - Yin, Shankai

AU - Wu, Hao

AU - Wang, Zhengmin

AU - Li, Huawei

AU - Rubinstein, Jay T.

AU - Lustig, Lawrence R.

AU - Chai, Renjie

AU - Chen, Zheng Yi

AU - Shu, Yilai

PY - 2026/1/9

Y1 - 2026/1/9

N2 - Background: Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss. Methods: A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75% agreement for inclusion. Findings: From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement). Conclusions: This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms. Funding: This work was supported by the National Natural Science Foundation of China, the German Research Foundation (DFG) via the Cluster of Excellence, and others.

AB - Background: Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss. Methods: A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75% agreement for inclusion. Findings: From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement). Conclusions: This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms. Funding: This work was supported by the National Natural Science Foundation of China, the German Research Foundation (DFG) via the Cluster of Excellence, and others.

KW - Translation to population health

KW - adeno-associated virus

KW - clinical trial

KW - expert consensus

KW - gene therapy

KW - hereditary hearing loss

KW - modified Delphi method

UR - https://www.scopus.com/pages/publications/105020827534

U2 - 10.1016/j.medj.2025.100886

DO - 10.1016/j.medj.2025.100886

M3 - Article

C2 - 41135524

AN - SCOPUS:105020827534

SN - 2666-6359

VL - 7

JO - Med

JF - Med

IS - 1

M1 - 100886

ER -

International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials

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Keywords

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