Gene therapy could soon help some people affected by genetic hearing loss, thanks to new findings from a joint research project by the Boston Children’s Hospital, Massachusetts Eye and Ear, and Harvard Medical School.
In the study, published in Nature Biotechnology, deaf mice treated with a synthetic virus were able to hear again. The mice were born deaf due to Usher syndrome, a genetic disorder that interferes with typical ear development. (Usher syndrome is found in three to six percent of human children who are born deaf, as well as another three to six percent of children who are born hard of hearing.) Usher syndrome causes ears to develop without the set of microscopic hairs in the inner ear that capture sound and head movement and convert them to neural signals for hearing and balance. The synthetic virus “infected” the mice with the instructions for building hair cells — instructions that are typically part of an animal’s genetic code, but are missing in individuals with Usher syndrome.
After the mice were treated with the virus, they were able to grow the hairs, and their hearing improved to the point that the mice could hear sounds as low as 25 decibels — about the volume of a whisper.
“It’s unprecedented, this is the first time we’ve seen this level of hearing restoration,” said researcher Dr. Jeffrey Holt, from Boston Children’s Hospital.
“We’ve really gotten a good understanding of the basic science, of the biology of the inner ear, and now we’re at the point of being able to translate that knowledge and apply it to human patients in the very near future.”
However, a number of critical unknowns remain. Before the researchers can move onto human subjects, they need to prove the synthetic virus is safe. The virus used in the study was based on adeno-associated virus, which has been widely used in other forms of gene therapy, including treatments that target rheumatoid arthritis, cystic fibrosis, liver disease, and vision disorders.
The researchers also need to prove that the effect is permanent or at least long-lasting. The mice treated in the study continued to experience hearing for more than six months.
Additional research will also help the researchers refine the ideal window of opportunity for treatment. During the initial research, the therapy worked in mice treated at birth. However, it failed when given just 10 days later. In humans, such an intervention might need to happen before birth, said Jonathan Ashmore, a professor at University College London’s Ear Institute. Human studies for the treatment are still years away.
Finally, this specific treatment would not work for every individual suffering from hearing loss or deafness. While the treatment was successful in mice affected by Usher syndrome, more than 100 difference genetic conditions can cause hearing loss, and a different therapy would need to be tailor-made for each one. Genetic hearing disorders affect 125 million people worldwide, according to the World Health Organization.
Andrew Forge, emeritus professor of auditory cell biology at University College London and an author of the Nature paper, said his field is trying to answer the question, “Can you manipulate the system to cure things that are wrong? These kinds of therapies, if there is going to be a therapy, will be the way it is going to be working.”