What they found
TL;DR (qwen3.6:35b): The dual-AAV gene therapy SENS-501 successfully restored hearing in deaf mice by delivering otoferlin to inner hair cells, with effects lasting up to 10 months. Preclinical safety studies in primates confirmed the treatment is well-tolerated and supports its progression to human clinical trials.
Congenital sensorineural hearing loss heavily impacts patients’ lives and their ability to communicate. Non-syndromic autosomal recessive deafness 9 (DFNB9), caused by mutations in OTOF, which encodes otoferlin, is one of the most prevalent forms of congenital hearing loss. SENS-501, a dual-AAV8 (adeno-associated virus 8) vector carrying the human OTOF coding sequence, was developed as a gene therapy to treat patients with DFNB9-related hearing loss. Intracochlear injection of SENS-501 in Otof -/- mice achieved targeted expression of otoferlin specifically in cochlear inner hair cells (IHCs), resulting in the restoration of auditory function observed as early as 3 weeks post administration and sustained for up to 10 months. SENS-501 was well tolerated following both local and systemic administrations in wild-type mice. GLP toxicology studies in non-human primates using the same surgical method and injection device used in DFNB9 patients confirmed that the intracochlear administration of SENS-501 is well tolerated and affords an adequate safety margin for human use. Vector biodistribution was largely restricted to the injection site. Collectively, these preclinical data support the development of SENS-501 as a safe and efficacious AAV-based treatment for DFNB9. A phase 1/2 clinical trial in children with severe-to-profound hearing loss due to otoferlin mutations is underway.
How this applies to our program
This study validates the feasibility of using AAV vectors for gene replacement in cochlear inner hair cells, a delivery strategy directly applicable to treating STRC/DFNB16-related deafness. The demonstrated safety margin and sustained functional recovery provide a critical precedent for developing similar therapies for STRC mutations.
Key numbers
- 3 weeks
- 10 months
- dual-AAV8
Links
- pubmed_id: https://pubmed.ncbi.nlm.nih.gov/42318138/
- DOI: https://doi.org/10.1016/j.omta.2026.201762
- PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13272531/
Connections
[source]auto-indexed 2026-06-20 by strc-lit-watch