Gene therapy restores hearing in mice

In a possible step toward treating genetic human deafness, scientists have used gene therapy to partially restore hearing in deaf mice.  

Some mice with genetic hearing loss could sense and respond to noises after receiving working copies of their faulty genes, researchers report July 8 in Science Translational Medicine. Because the mice’s mutated genes closely correspond to those responsible for some hereditary human deafness, the scientists hope the results will inform future human therapies.

“I would call this a really exciting big step,” says otolaryngologist Lawrence Lustig of Columbia University Medical Center.

The ear’s sound-sensing hair cells convert noises into information the brain can process. Hair cells need specific proteins to work properly, and alterations in the genetic blueprints for these proteins can cause deafness. To combat the effects of two such mutations, the scientists injected viruses containing healthy genes into the ears of deaf baby mice. The virus infected some hair cells, giving them working genes.

The scientists tried this therapy on two different deafness-causing mutations. Within a month, around half the mice with one mutation showed brainwave activity consistent with hearing and jumped when exposed to loud noises. Treated mice with the other mutation didn’t respond to noises, but the gene therapy helped their hair cells — which normally die off quickly due to the mutation — survive. All of the untreated mice remained deaf.

The mice that recovered hearing received a partial fix. Most of their inner hair cells, which allow basic hearing, used the new genes. But few outer hair cells, which amplify noises, accepted the viral delivery. It’s hard to get outer hair cells to respond to gene therapy, Lustig says. Still, inner hair cells control most sound transmission, he says.

The scientists hope to eventually identify the right virus and genetic instructions to treat all hair cells and get complete recovery of hearing, says study coauthor Jeffrey Holt, a neuroscientist at Boston Children’s Hospital. The team’s immediate goals are to improve the viral infection rate and test if the treatment can last for long time periods, Holt says. He says the viruses used to deliver the genes are safe and already used in human gene therapies.

Many other genetic defects can cause deafness, and each one will require separate research to determine optimal conditions for gene therapy. But along with evidence from earlier studies, these results show that gene therapy can treat deafness, Lustig says.

Gene therapies must work as well as existing cochlear implant technologies to become a good treatment option, Lustig adds. But a functioning inner ear would ultimately do a far better job than any cochlear implant could, he says.  “Ultimately, we’ll get there.”