A gene therapy trial in the UK – what does this mean?

This month the news that a British deaf child had successfully been given gene therapy through clinical trials made headline news. It's the first time gene therapy has been used on a deaf child in the UK. This blog provides info about the trial and what it means for deaf children and young people.

What is gene therapy?

This is when genes that cause a condition are inactivated or replaced by ‘normal’ genes. One way this can be done is by injecting a virus into a patient’s body. The virus acts as a carrier of the new gene, which is inserted into a patient’s DNA (their genetic code). This is the process being used in the Decibel Therapeutics trial.

For more information about gene therapy visit: https://www.yourgenome.org/facts/what-is-gene-therapy/

Could this new treatment be used with deaf children?

Trials in Cambridge and London are testing out gene therapy for children who have a particular type of genetic deafness caused by lack of a protein called Otoferlin (OTOF), leading to severe or profound deafness from birth. Otoferlin encodes sounds within the inner ear and allows nerve signals to be sent from the cochlea to the brain. The gene therapy developed by biotechnology company, Regeneron, inserts ‘normal’ genes into the cochlear hair cells so that Otoferlin is produced, enabling signalling between the ear and the brain.

The gene therapy will only be effective for people who have a variation in the OTOF gene. If you are deaf because of a different gene, then you wouldn't be eligible to take part in the trial. Only a small percentage of children are deaf because of a variation in the OTOF gene.

It's expected that the trials will include a small number of children, ranging from 0 to 17. Children aged 7 or over will need to provide their own consent along with that of their parents.

How do I find out if my child is eligible for these trials?

If you don't know the cause of your child’s deafness then you should contact your audiologist or GP as a first step. If it's believed to due to a genetic cause then your child can be referred for genetic testing.

If you know that your child is deaf because of a variation in the OTOF gene, then you can get in touch with one the clinical trial sites for more information. See https://clinicaltrials.gov/study/NCT05788536?cond=OTOF Gene Mutation&rank=3#contacts-and-locations for contact details.

If the trial was effective, would it mean a child would no longer be deaf?

No, full hearing is not likely, but the severity of deafness could be much reduced. The company behind the trials describes itself as trying to provide ‘durable hearing’. Gene therapy trials with deaf mice have not completely restored hearing and we’d expect to see similar results with humans.

Additionally, where gene therapy is carried out on older young people, research suggests it might not compensate for permanent changes in how the brain is wired. Where people have grown up deaf, auditory signals may be processed differently between the ear and the brain from how they are in hearing people. It's believed that these can't be reversed. This means that a deaf person could hear more, but it would be more challenging to process new sounds effectively and understand what they mean.

Are there any risks to gene therapy?

As with many medical treatments, it is not risk-free. There have been cases of adverse immune reactions to gene therapy which can create dangerous side effects, including death in rare cases. However, much work has been done in the past couple of decades to find safer ways of carrying out gene therapy. The number of trials being granted permission in recent years by regulators suggests that the most serious safety concerns have now been addressed.

Are the trials controversial?

They may be, depending on your point of view. Some people do not believe that deafness is something that needs to be cured or eradicated. Many deaf people live happy and fulfilled lives and see being deaf as a positive part of their identity. Other people believe that deaf children face too many barriers in life and the best way to overcome these barriers is to find medical treatments for their deafness.

Our view is that families and young people should be free to make the decisions that they believe are best for them. We, however, believe that these should be fully informed decisions. Parents or young people should be made aware of any risks of complications, the limitations of the treatment, and above all understand that being deaf is not a barrier in itself to a happy and fulfilled life.

What about other deaf genes? Will gene therapy be developed for these too?

It's likely that gene therapy will be developed for other genes that cause deafness. However, these may still be some way off. We believe it's important that families are focused on what they can do now for their child and not hold out for a treatment that might take many years to arrive.

 

This blog has been written by Martin McLean, our Senior Policy Advisor. Martin has a degree in Genetics and has previously run information projects on genetics for deaf people and their families.