Evidence map›Paper›PMID 38839897›Full record

Trial reportNature medicine2024

Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

Hui Wang, Yuxin Chen, Jun Lv, Xiaoting Cheng, Qi Cao, Daqi Wang, Longlong Zhang, Biyun Zhu, Min Shen, Chunxin Xu and 20 more

Abstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. A Systematic Review of Genes Affecting Endocochlear Potential.Journal of the Association for Research in Otolaryngology : JARO · 2026
    Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Article
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  9. Article
  10. Review
  11. Tinnitus.Nature reviews. Disease primers · 2026
    Review
  12. Stem cell-based and gene editing strategies in the treatment of congenital and acquired sensorineural hearing loss: a narrative review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Review
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Hui Wang *ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Yuxin Chen *ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Jun Lv *ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Xiaoting Cheng *ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Qi Cao *ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Daqi WangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Longlong ZhangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Biyun ZhuENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Min ShenShanghai Rehabilitation Institute for the Exceptional Children, Shanghai, China.
Chunxin XuShanghai Rehabilitation Institute for the Exceptional Children, Shanghai, China.
Mengzhao XunENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Zijing WangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Honghai TangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Shaowei HuENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Chong CuiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Luoying JiangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Yanbo YinENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Luo GuoENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Yi ZhouENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Lei HanENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Ziwen GaoENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Jiajia ZhangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Sha YuENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Kaiyu GaoShanghai Refreshgene Therapeutics Co. Ltd., Shanghai, China.
Jinghan WangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Bing ChenENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China.
Wuqing WangENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China. wwuqing@eent.shmu.edu.cn.
Zheng-Yi ChenDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, MA, USA. zheng-yi_chen@meei.harvard.edu.ORCID 0000-0002-1452-4193
Huawei LiENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China. hwli@shmu.edu.cn.
Yilai ShuENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, Fudan University, Shanghai, China. yilai_shu@fudan.edu.cn.ORCID 0000-0001-8893-434X

Funding

Fudan University yg2022-23Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2020YFA0908201Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2021YFA1101302Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2023YFC2508400National Natural Science Foundation of China (National Science Foundation of China) 82192864National Natural Science Foundation of China (National Science Foundation of China) 82225014 and 82171148Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 21S11905100 and 23J31900100Shanghai Municipal Education Commission 2023ZKZD12
6 · The paper itself

Abstract

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

Indexed as

DependovirusGenetic TherapyAdolescentChildChild, PreschoolDeafnessEvoked Potentials, Auditory, Brain StemFemaleGenes, RecessiveGenetic VectorsHumansMaleTreatment Outcome

Identifiers

PMID38839897
PMCPMC11271389

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.