CAMBRIDGE, ENGLAND — Addenbrooke’s Hospital in Cambridge is part of an landmark global trial that seeks to restore hearing in children with a rare genetic condition. The trial is exploring the potential of gene therapy to restore hearing in children with severe to profound hearing loss due to auditory neuropathy, a condition that disrupts nerve impulses from the inner ear to the brain.
Up to 18 children from the UK, Spain, and the USA, all under the age of 18, will be part of this groundbreaking trial, which will span five years to assess the extent of hearing improvement.
Clinical Trial: Gene Therapy for Hearing Loss
Auditory neuropathy, often stemming from mutations in the OTOF gene, affects around 20,000 people across the US and several European countries. The OTOF gene usually produces a protein called otoferlin, enabling communication between inner ear cells and the hearing nerve.
Professor Manohar Bance, an ear surgeon at Cambridge University Hospitals NHS Foundation Trust, leads the trial, emphasizing that children with OTOF gene mutations are born with profound hearing loss, which often goes unnoticed in standard hearing screenings for newborns.
“Children with a variation in the OTOF gene are born with severe to profound hearing loss, but they often pass the newborn hearing screening so everyone thinks they can hear. The hair cells are working, but they are not talking to the nerve. Gene therapy for otoferlin deficiency is the right starting point for young children because it’s among – if not the most – simple approaches for treating hearing loss; everything else should be intact and working normally. Although experimental, the therapy could also potentially result in better quality hearing compared to cochlear implants. But we have a short time frame to intervene because the young brain is developing so fast.
–Prof. Manohar Bance
The trial uses gene therapy to deliver a functional copy of the defective OTOF gene, utilizing a modified, non-pathogenic virus. Administered via an injection into the cochlea during surgery, the procedure closely resembles cochlear implant surgery, the current standard treatment for OTOF-related hearing loss.
The trial will consist of three parts, which must be done in order, with children receiving:
- A starting dose of gene therapy (DB-OTO) in one ear only.
- A higher dose of gene therapy in one ear only, following proven safety of the starting dose.
- Gene therapy in both ears with the optimal dose selected after ensuring the safety and effectiveness of DB-OTO in parts 1 and 2.
If the gene therapy doesn’t prove effective within six months, families can opt for a cochlear implant. Successful gene therapy could pave the way for treating other genetic hearing conditions, a significant advancement in the field of hearing loss treatments. The trial is sponsored by Regeneron Pharmaceuticals (which completed its acquisition of Decibel Therapeutics in September), with support from the National Institute for Health and Care Research (NIHR) and is conducted at Cambridge’s Clinical Research Facility.
This ambitious trial offers hope to children with OTOF-related hearing loss and raises prospects for a future where gene therapy treatments provide long-lasting solutions for hearing impairments, unlike hearing aids that primarily manage symptoms.
All clinical trials that take place at Cambridge University Hospitals NHS Foundation Trust (CUHFT) are independently assessed for safety and quality by the Health Research Authority and Research Ethics Committee and complete the required legal and regulatory approvals before CUHFT agrees to participate. A team at the hospital has reviewed the safety protocols and all the necessary information; the trial will be performed and monitored by an experienced team of doctors, nurses and clinical support staff. All participating families give informed consent before treatment.
For more information about the CHORD clinical trial (NCT0578836), including eligibility criteria, please visit: Study Record | ClinicalTrials.gov
For patient materials, see the SenseLab website
Source: CUH
