Gene therapy restores hearing in mice

Researchers injected missing proteins into the ears of mice with two genetic mutations found in humans and restored at least part of their sense of hearing.

By Stephen Feller

WASHINGTON, July 9 (UPI) -- Researchers have restored hearing in mice with two versions of a genetic mutation that, in humans, causes gradual hearing loss during childhood.

The successful work with mice is focused on a gene critical to hearing, TMC1, which encodes a protein that allows physical stimulation of "hairs" in the ear to be translated into sounds understood by the brain.


Hair cells in the ear contain projections called microvilli, each of which has a channel at its end for the TMC1 protein. When sound waves enter the ear and pass over the microvilli, they wiggle, allowing calcium to enter the cells, which generates an electrical signal sent to the brain that is translated into sound.

Two types of genetic mutations, one recessive, with the gene deleted, and one dominant, with an altered amino acid, lead to what accounts for 4 to 8 percent of genetic deafness cases. The recessive mutation, which is more common, causes hearing loss by the time a child is 2 years old. The dominant version progressively causes children to lose their hearing starting around 10 or 15 years old.

Researchers inserted the healthy gene into an engineered virus using a genetic sequence called a promoter that allows the TMC1 gene to be turned on only in the inner ear. This virus was then injected into the ears of mice with both mutations.


In the mice with the recessive form of the mutation, researchers were able to restore hearing beginning with sounds of 80 decibels by testing their hearing in a "startle box." They knew the mice could hear if they jumped at the sound of loud, abrupt noises while in the box.

Mice with the dominant form also received injections, though researchers inserted the related TMC2 gene into the virus. Hearing was partially restored in these mice as well.

"Our gene therapy protocol is not yet ready for clinical trials -- we need to tweak it a bit more -- but in the not-too-distant future, we think it could be developed for therapeutic use in humans," Jeffrey Holt, an associate professor of otology and laryngology at Harvard Medical School, said in a press release. "I can envision patients with deafness having their genome sequenced and a tailored, precision-medicine treatment injected into their ears to restore hearing."

The researchers plan to continue following the mice to see if hearing is retained over a period of time longer than the two months of observation in the study, and hope to begin clinical trials in 5 to 10 years, Holt said.

The study is published in Science Translational Medicine.


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