Gene therapy helps deaf mice hear sounds as soft as whispers

Child's ear
Harvard scientists are investigating gene therapy for restoring hearing in some people with a hereditary form of deafness.

Scientists at Harvard Medical School are reporting today that they’ve perfected a form of gene therapy originally developed to restore hearing, and as a result, genetically deaf mice are able to hear down to 25 decibels. That’s the equivalent of a whisper.

The researchers, who describe the technique in the journal Nature Biotechnology, say the key to making the gene therapy work is a vector they developed called Anc80. The vector carries a therapeutic gene into the cochlea’s outer ear cells, which are notoriously hard to access.

"Outer hair cells amplify sound, allowing inner hair cells to send a stronger signal to the brain,” says Gwenaëlle Géléoc, of the Department of Otolaryngology and F.M. Kirby Neurobiology Center at Boston Children's Hospital, in a press release. “We now have a system that works well and rescues auditory and vestibular function to a level that's never been achieved before.”

The research team, which included scientists from Massachusetts Eye and Ear, tested the gene therapy technique in a mouse model of Usher Syndrome, a genetic disease that damages both hearing and vision. People with the disease have a gene mutation that renders the protein harmonin useless, which in turn cripples the hair cells that are responsible for receiving sound signals and sending them to the brain.

Géléoc and colleagues used the new vector to deliver a corrected version of the gene, called Ush1c, into the ear. Soon after, the ears’ inner and outer hair cells began to produce normal harmonin, they observed. Hearing tests performed on the mice showed that animals born deaf were starting to hear, and some could hear very soft sounds, just like normal mice.

Gene therapy has generated excitement throughout the scientific world for its potential to cure deafness. In 2014, Harvard scientists worked with investigators at the University of Michigan Medical School's Kresge Hearing Research Institute to investigate the role of another hearing-related protein, NT3, and they determined it also has the potential to be boosted via gene therapy. Other approaches are aimed at prompting hair cells in the ear to regenerate. Harvard researchers have discovered, for example, that drugs known as Notch inhibitors can prompt existing cells in the ear to become hair cells, restoring some hearing in mice.

The Harvard team reporting this most recent success with gene therapy had used a similar technique to restore hearing in 2015, but they believe the new vector they developed is restoring a higher level of hearing. They also reported a bonus benefit: Mice treated with the corrected Ush1c gene also showed improvements in balance, which is often impaired in Usher Syndrome.

That’s heartening to physicians like Margaret Kenna, who specializes in hearing loss at Boston Children’s. Kenna believes gene therapy could someday replace the cochlear implants that are often used to restore hearing in young people. "Cochlear implants are great, but your own hearing is better in terms of range of frequencies, nuance for hearing voices, music and background noise, and figuring out which direction a sound is coming from,” Kenna says in the release. “In addition, the improvement in balance could translate to better and safer mobility for Usher Syndrome patients."