In this project, Professor Els Henckaerts at KU Leuven, Belgium, is testing gene therapy as a method to treat hearing loss caused by mutations in the ‘stereocilin’ gene.
Project start date: March 2026
Project end date: February 2028
About the project
One of the most common genetic causes of childhood hearing loss is a mutation in the stereocilin gene, which leads to a type of hearing loss called ‘DFNB16’. Current care for this condition involves hearing aids. However, many people with DFNB16 still struggle to understand speech in noisy environments because hearing aids cannot fully replicate the ear’s natural ability to filter and process sounds.
Stereocilin is a protein found in the outer hair cells (OHCs) of the inner ear. These cells play a special role in hearing by amplifying quiet sounds and sharpening the ability to distinguish different sound pitches. When stereocilin is missing or not working, the OHCs cannot amplify sound properly, leading to difficulties in hearing soft sounds and high-pitched tones.
In this project, the researchers will investigate whether gene therapy to introduce a functional stereocilin gene can restore hearing.
How it works
Gene therapy aims to restore the function of the OHCs by delivering a healthy copy of the stereocilin gene to the affected cells. This therapy uses a harmless virus as a delivery vehicle to transfer the working gene into the patient’s OHCs. The stereocilin gene is large, so it is split into two parts and delivered through the two halves of the cell. The team will use a technology called “split-inteins” to split the stereocilin protein into two pieces that will then come together and form the complete, functional stereocilin protein in the target OHCs.
An important challenge for this therapy is determining the optimal time window for treatment. In studies with mice, successful rescue of hearing has only been demonstrated when gene therapy is administered very early, right after birth. It is not yet known if treatment at later stages, which would be more relevant for treating children, will be effective.
What will this research achieve?
DFNB16 is estimated to account for about 1–2% of all childhood hearing loss cases, meaning thousands of children and adults in the US and EU are affected by this condition.
Stereocilin gene therapy could be a breakthrough for people with DFNB16. By directly addressing the root cause of this type of hearing loss, gene therapy offers hope for restoring or preserving hearing and improving quality of life for those affected.
This project will also help us to better understand the critical period for therapeutic intervention and will test whether later treatment can also be beneficial, which is important for translating this therapy for humans.
About the researchers
Professor Els Henckaerts leads the Trellis research group at KU Leuven. The team includes Wout Verscheure (PhD student), Thomas Matheussen, (research technician) and Simon Sinnaeve (PhD student).
My motivation has always been to close the gap between what is discovered at the lab bench and what is possible at the patient’s bedside. Genetic hearing loss is complex, but the potential of AAV technology to deliver large, critical genes gives us a clear path forward. For me, the true purpose of this work is about translating that science into a tangible, life-changing reality for individuals and families.”
Dr Filip de Vin leads the inner ear gene therapy programme within Trellis Research Group at KU Leuven.
My ultimate ambition is to see STRC gene therapy move from the laboratory into the clinic to give children with DFNB16 a genuine chance at restored hearing. Every step we take here brings us closer to a first-in-human treatment that could transform the lives of thousands of families worldwide.”
