Gene therapy restores hearing in both ears of children with rare genetic deafness

A gene therapy has restored hearing in five children, marking the first successful treatment in both ears following earlier single-ear trials.

A clinical trial led by researchers from Fudan University in Shanghai, China, and the Massachusetts Eye and Ear Infirmary, Boston, has successfully improved hearing in all five participants, aged one to 11, who have congenital deafness caused by a mutation in the OTOF gene. Early results from the trial demonstrated significant improvements in speech perception and sound localisation, even in noisy environments.

'Restoring hearing in both ears of children who are born deaf can maximise the benefits of hearing recovery,' said co-senior author of the study published in Nature Medicine, Dr Yilai Shu from Fudan University. 'These new results show this approach holds great promise and warrant larger international trials.'

This study builds upon previous work by the same team, who initially presented their results in October 2023 claiming they were the first in the world to report clinical data using gene therapy to restore hearing (see BioNews 1214). They subsequently reported further improvements earlier this year in five out of six children who received the gene therapy in one ear (see BioNews 1224).

The gene therapy involves injecting an inactive virus carrying a working version of the OTOF gene directly to cells in the inner ear. These cells are then able to generate functional otoferlin protein, which is essential for transmitting sound signals from the hair cells in the inner ear to the neurons that carry this information to the brain.

Now, the team is the first to treated both ears simultaneously, with all five children treated having their hearing restored. In addition, the team reported that the children all gained the ability to determine the location that sounds came from and also reported better speech perception in noisy environments.

However, there was a slight increase in side effects reported due to the patients' heightened immune response from doubling the dose of the inactive virus used as the delivery method, yet there were no severe reactions or toxicity reported.

The oldest patient was 11 years old, which is considered outside the optimal range for language acquisition, and after which a child typically struggles to learn to talk. However, after treatment, this child began using single words and was able to start speech training.

'This would suggest that maybe there's some plasticity in the brain in a patient that we could remodel somehow in the future,' Dr Zheng-Yi Chen, co-senior author from the Massachusetts Eye and Ear Infirmary and Harvard Medical, School told the Harvard Gazette. 'This opened up a new field for us to explore.'

Early results from a similar trial conducted in one ear of an 11-year old patient at the Children's Hospital of Philadelphia, Pennsylvania, using a different form of OTOF gene therapy has demonstrated similar results (see BioNews 1224), as has a trial which is taking place in the UK, Spain and the USA (see BioNews 1238 and 1212).

These trials may be demonstrating the potential of gene therapy to restore hearing for congenital deafness, however, longer follow-up durations and bigger trials using larger sample sizes are necessary to answer questions about the longevity and potential risks of this treatment.