Thursday, April 23, 2026
No menu items!
HomeNatureMulticentre gene therapy for OTOF-related deafness followed up to 2.5 years

Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years

  • Yasunaga, S. et al. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat. Genet. 21, 363–369 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lv, J. et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet 403, 2317–2325 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, H. et al. Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results. Nat. Med. 30, 1898–1904 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cheng, X. et al. Gene therapy vs cochlear implantation in restoring hearing function and speech perception for individuals with congenital deafness. JAMA Neurol. 82, 941–951 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qi, J. et al. AAV gene therapy for autosomal recessive deafness 9: a single-arm trial. Nat. Med. 31, 2917–2926 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Morton, C. C. & Nance, W. E. Newborn hearing screening—a silent revolution. N. Engl. J. Med. 354, 2151–2164 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lieu, J. E. C., Kenna, M., Anne, S. & Davidson, L. Hearing loss in children: a review. JAMA 324, 2195–2205 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Sloan-Heggen, C. M. et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum. Genet. 135, 441–450 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rodríguez-Ballesteros, M. et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum. Mutat. 29, 823–831 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Iwasa, Y. I. et al. OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients. PLoS ONE 14, e0215932 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Choi, B. Y. et al. Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan. Clin. Genet. 75, 237–243 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Akil, O. et al. Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model. Proc. Natl Acad. Sci. USA 116, 4496–4501 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Q. J. et al. High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder. Clin. Genet. 90, 238–246 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roux, I. et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell 127, 277–289 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, L. et al. Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates. Mol. Ther. Methods Clin. Dev. 31, 101154 (2023).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reisinger, E. & Trapani, I. Gene therapy proves successful in treating hereditary deafness. Lancet 403, 2267–2269 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Necula, V. et al. Vertigo associated with otosclerosis and stapes surgery—a narrative review. Medicina 59, 1485 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quatre, R., Eklöf, M., Wales, J. & Bonnard, Å Long-term hearing outcomes following cochlear implantation in far advanced otosclerosis. Otolaryngol. Head Neck Surg. 172, 2065–2071 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Terry, B., Kelt, R. E. & Jeyakumar, A. Delayed complications after cochlear implantation. JAMA Otolaryngol. Head Neck Surg. 141, 1012–1017 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Keithley, E. M. Pathology and mechanisms of cochlear aging. J. Neurosci. Res. 98, 1674–1684 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ford, C. L. et al. The natural history, clinical outcomes, and genotype–phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review. Hum. Genet. 142, 1429–1449 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paping, D. E. et al. Distortion product otoacoustic emissions in screening for early stages of high-frequency hearing loss in adolescents. Noise Health 24, 20–26 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goutman, J. D., Elgoyhen, A. B. & Gomez-Casati, M. E. Cochlear hair cells: the sound-sensing machines. FEBS Lett. 589, 3354–3361 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Farinetti, A., Raji, A., Wu, H., Wanna, B. & Vincent, C. International consensus (ICON) on audiological assessment of hearing loss in children. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 135, S41–S48 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Maddox, R. K. & Lee, A. K. C. Auditory brainstem responses to continuous natural speech in human listeners. eNeuro https://doi.org/10.1523/ENEURO.0441-17.2018 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gransier, R., Hofmann, M., van Wieringen, A. & Wouters, J. Stimulus-evoked phase-locked activity along the human auditory pathway strongly varies across individuals. Sci. Rep. 11, 143 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abdala, C. & Visser-Dumont, L. Distortion product otoacoustic emissions: a tool for hearing assessment and scientific study. Volta Rev. 103, 281–302 (2001).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. World Report on Hearing (World Health Organization, 2021).

  • Robbins, A. M., Renshaw, J. J. & Berry, S. W. Evaluating meaningful auditory integration in profoundly hearing-impaired children. Am. J. Otol. 12, 144–150 (1991).

    PubMed 

    Google Scholar
     

  • Robbins, A. M. & Osberger, M. J. Meaningful Use of Speech Scale (MUSS) (Indiana University School of Medicine, 1990).


    Google Scholar
     

  • Pennini, P. T. M. & Almeida, K. Speech, Spatial and Qualities of Hearing Scale in assessing the benefit in hearing aid users. Codas 33, e20190196 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Galvin, K. L. & Noble, W. Adaptation of the speech, spatial, and qualities of hearing scale for use with children, parents, and teachers. Cochlear Implants Int. 14, 135–141 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Archbold, S., Lutman, M. E. & Nikolopoulos, T. Categories of auditory performance: inter-user reliability. Br. J. Audiol. 32, 7–12 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McDaniel, D. M. & Cox, R. M. Evaluation of the Speech Intelligibility Rating (SIR) test for hearing aid comparisons. J. Speech Hear. Res. 35, 686–693 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fu, Q. J., Zhu, M. & Wang, X. Development and validation of the Mandarin speech perception test. J. Acoust. Soc. Am. 129, EL267-273 (2011).

    Article 

    Google Scholar
     

  • Cheng, X. et al. Music training can improve music and speech perception in pediatric Mandarin-speaking cochlear implant users. Trends Hear. 22, 2331216518759214 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • RELATED ARTICLES

    Most Popular

    Recent Comments