Year: 2025
Type: article
Abstract: Gene therapy has recently restored natural audibility in humans with OTOF-gene mutations. This biological restoration of hearing is different from cochlear implantation (CI) that produces artificial hearing via electric stimulation of the auditory nerve. In three published trials, 21 DFNB9 patients show 244 grade I/II adverse events (AEs), 2 grade III AEs and no serious AEs. The average gene therapy effect is substantial (52.4-dB improvement from baseline complete deafness), rapid (0.74-month time constant), and stable over the initial six months. However, individual outcomes vary from restored normal audibility (≤20 dB HL) to severe hearing loss (≥80 dB HL). Here critical knowledge gaps in gene therapy are identified such as understanding the individual variability, assessing temporal processing, and comparing efficacy with cochlear implantation. It is predicted that gene therapy will include patients with less than complete hearing loss and target other monogenic forms of congenital deafness. Advanced technologies in minimally invasive drug delivery and gene editing will further increase the safety, efficacy and applicability of gene therapy for hearing loss. Cochlear implantation likely remains the standard intervention for severe-to-profound hearing loss, but gene therapy will emerge as a viable alternative in treating monogenic forms of deafness.
Source: Advanced Science
Institutions: University of California, Irvine, Beijing Institute of Technology, Zhuhai People's Hospital, National Taiwan University, National Taiwan University Hospital, Shanghai Medical College of Fudan University, Fudan University, Eye & ENT Hospital of Fudan University, University of Electronic Science and Technology of China, Nantong University, Zhongda Hospital Southeast University, State Key Laboratory of Digital Medical Engineering, Southeast University
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Funders: Eli Lilly and Company, Regeneron Pharmaceuticals, National Natural Science Foundation of China, Government of Jiangsu Province, Karolinska Institutet, Natural Science Foundation of Jiangsu Province, Natural Science Foundation of Beijing Municipality, Taishan Scholar Foundation of Shandong Province, National Key Research and Development Program of China
OpenAlex ID: W4414420308