Gene therapy enables deaf baby to hear

A child born with congenital deafness, has had her hearing restored after participating in the first phase of a gene therapy trial.

Her deafness was due to a variant of the OTOF gene, which causes the hair cells in the cochlea in the inner ear to not communicate correctly with the auditory nerve. She received gene therapy at as part of international CHORD clinical trial taking place in the UK, Spain and the USA, that replaced the faulty OTOF gene with a working copy, in the inner ear (see BioNews 1212). Similar results have been seen in other clinical trials using different gene therapies targeting the OTOF gene, in the USA and China (see BioNews 1214).

'Gene therapy has been the future of otology and audiology for many years and I'm so excited that it is now finally here. This is hopefully the start of a new era for gene therapies for the inner ear and many types of hearing loss', said Professor Manohar Bance, chief investigator of the CHORD clinical trial and ear surgeon at Cambridge University Hospitals NHS Foundation Trust.

One in every 500 children are born with hearing loss, which is called congenital hearing loss. Most of these cases are caused by genetic variations, with mutations in the OTOF gene accounting for one to eight percent of congenital hearing loss.

The treatment, which took place at Addenbrooke's Hospital in Cambridge, involved the injection of a modified harmless virus with a working copy of the OTOF gene into the right inner ear, under general anaesthesia, shortly before the child's first birthday. A cochlear implant was fitted in her left ear, to ensure she could hear as soon as possible.

Within four weeks of having the treatment, the toddler responded to sound, even with the cochlear implant switched off. She improved continuously and after six months clinicians confirmed she had close to normal hearing levels for soft sounds. Now, at 18 months old, she has started to speak.

The CHORD clinical trial will have three phases and include 18 children worldwide. The first phase, in which this child participated, consists of receiving a low dose of the gene therapy to one ear. The second phase will have a higher dose administered to one ear, following proven safety of the starting dose. Finally, if the previous phases are proven safe, the third phase will consist of injecting the therapy in both ears.

A second child enrolled in the CHORD clinical trial is showing similar results six weeks after treatment.

Professor Bance added: 'We have a short time frame to intervene because of the rapid pace of brain development at this age. Delays in the diagnosis can also cause confusion for families as the many reasons for delayed speech and late intervention can impact a children's development.'