A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.
Publication/Presentation Date
8-19-2026
Abstract
PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice.
RECENT FINDINGS: Early clinical trials targeting OTOF-related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access.
SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.
ISSN
1531-6998
Published In/Presented At
Dunn, E. C., Short, S. H., & Samy, R. N. (2026). A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations. Current opinion in otolaryngology & head and neck surgery, 10.1097/MOO.0000000000001155. Advance online publication. https://doi.org/10.1097/MOO.0000000000001155
Disciplines
Medicine and Health Sciences
PubMedID
42614064
Department(s)
Department of Surgery, Department of Surgery Faculty, Department of Surgery Residents, Division of Otolaryngology, Fellows and Residents, USF-LVHN SELECT Program, USF-LVHN SELECT Program Faculty, USF-LVHN SELECT Program Students
Document Type
Article