In this project, Dr Christopher Cunningham and Dr Adele Moatti at the University of Pittsburgh, USA, are developing a gene therapy as a method to treat hearing loss caused by mutations in the TOMT gene.
Project start date: March 2026
Project end date: February 2028
About the project
There is an urgent need for safe and effective therapies that restore natural hearing. Gene therapy is a promising approach, as shown by the recent development of gene therapy for Otoferlin (OTOF)-related hearing loss. However, hearing loss can result from mutations in more than 100 different genes, each affecting the auditory system in distinct ways. Therefore, a one-size-fits-all strategy is unlikely to succeed. Instead, precise therapies targeting specific genetic causes are needed.
In this project, Dr Cunningham and Dr Moatti are developing a gene therapy designed to correct mutations in TOMT by delivering healthy copies of the TOMT gene directly to hair cells. TOMT is an essential gene for the function of sound-sensing cells (called hair cells) located in the cochlea of the inner ear. People with TOMT-linked deafness are born profoundly deaf because their hair cells cannot transmit sound signals to the brain.
How it works
In this study, the researchers will deliver their gene therapy to the inner ears of animal models and test its specificity, safety, and effectiveness across multiple doses. They will assess how the therapy distributes across the cochlea, whether it targets hair cells specifically, and whether any unwanted short-term or long-term effects occur in auditory and non-auditory tissues.
What will this research achieve?
These studies are essential to prepare for clinical trials and to demonstrate that the therapy can be translated safely and effectively to humans. Ultimately, this work aims to advance a treatment to restore natural hearing in individuals with TOMT-linked deafness, with broader implications for many other forms of inherited hearing loss. In the long term, this approach may also benefit individuals with acquired hearing loss or tinnitus when these conditions involve damage to hair cells.
About the researchers
Dr Christopher Cunningham is an Assistant Professor in the Department of Otolaryngology at the University of Pittsburgh, and the Pittsburgh Hearing Research Centre.
I hope our work will have a lasting impact on advancing the understanding of normal and pathological function of the sound-sensing hair cells, the cochlea, and the auditory system, and that it will motivate others to dig even deeper. Equally important is the hope that our work will contribute to the development of therapies that meaningfully improve the lives of people with hearing loss.”
Dr Adele Moatti is an Assistant Professor in the Department of Otolaryngology at the University of Pittsburgh, and the Pittsburgh Hearing Research Center.
RNID funding represents an incredible opportunity to advance translational hearing research that would otherwise be difficult to achieve. We are deeply grateful for the support that has brought the Cunningham and Moatti labs together to collaboratively advance gene therapy approaches for hearing loss associated with TOMT mutations.”
