Scientifically Speaking | A groundbreaking gene therapy trial enables deaf children to hear for the first time

For most of us, the joys of hearing a loved one’s voice or the simple pleasure of listening to music is a given. But for five children in China who were born deaf, this is now a reality thanks to a groundbreaking development in gene therapy. This innovative treatment, reported on June 5 in the scientific journal Nature Medicine, delivered a working copy of a crucial gene to the inner ear to allow these deaf children to hear for the first time.

Hearing loss affects over 430 million people, or more than 5 percent of the world’s population, according to the World Health Organization. This includes 34 million children who suffer from hearing loss. Approximately 26 million people have hearing loss from birth, with 60 percent of these cases stemming from genetic factors.

One genetic factor causing hearing loss at birth is called autosomal recessive deafness 9 (DFNB9), which occurs due to a mutation that leads to a faulty otoferlin protein. This genetic mutation affects 2-8 percent of children born deaf worldwide.

Otoferlin is essential for the proper functioning of hair cells in the ear, which detect sound and send signals to the brain. Without this protein, children with DFNB9 experience hearing loss from birth or early childhood.

The five children involved in the gene therapy trial reported in Nature Medicine, aged 1 to 11, were all born with DFNB9 and because they lacked functioning otoferlin, they could not hear.

The gene therapy uses tiny, engineered viruses to carry the working otoferlin gene into the hair cells of the inner ear. The viruses used in the trial bring the gene directly to the cells that need it. Since the otoferlin gene is too big for a single virus, it’s split into two parts and delivered using two separate viruses in one surgery. Once inside the cells, the two parts come together, making the gene work properly again.

In an earlier trial, researchers successfully restored hearing in one ear of other deaf children. Building on this success, the latest trial treated both ears of five children. This approach helps the children hear more evenly and effectively.

Six months after receiving the gene therapy, the children’s hearing improved significantly. Their hearing reached about half of normal levels, allowing them to hear conversations at regular volumes. They also showed great improvements in understanding speech and finding where sounds came from. These skills help to understand conversations in noisy places, enjoy music, and stay safe by detecting warning signals.

This was a follow-up to an earlier trial that began in December 2022, in which the research team successfully performed gene therapy in just one ear, to reduce the risk of side effects by using a lower dose. Encouraged by the hearing improvements and lack of serious side effects, researchers now plan to treat the second ear of the children from the first trial.

This trial is part of a larger effort to expand gene therapy for hereditary deafness worldwide. Similar trials are happening in other countries, and their success could lead to treatments for other genetic forms of deafness.

Researchers are making treatment responses more consistent and addressing the distinct types of hearing loss. They will also study how long the restored hearing will last.

Early detection of genetic causes through newborn screening and better genetic test interpretations are crucial for effective treatment. Different genetic mutations causing hereditary hearing loss will need different treatment approaches. Often, sensory cells are lost before treatment, so methods for regenerating these cells will be needed.

It’s early days, but the progress so far is fantastic. This breakthrough brings us closer to a future in which a world of sound is unlocked for many more people.

Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.