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Hearing Restored in Mice with Genetic Deafness using Gene Therapy

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Justine Alford

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985 Hearing Restored in Mice with Genetic Deafness using Gene Therapy
Sensory hair cells treated with TMC2 gene therapy. Charles Askew.

Around 360 million people, or five percent of the global population, have disabling hearing loss. While half of these cases are avoidable through prevention strategies, such as vaccination and reducing exposure to loud noises, many are genetic and can be inherited. But hope could well be on the way, as scientists have successfully managed to restore hearing in mice with a type of genetic deafness.

The work is very much proof-of-principle at this stage, but the researchers think that with further fine-tuning, their technique – gene therapy – could eventually make its way into clinical trials and help people with deafness caused by faulty genes.


The gene on which the researchers chose to focus for their study is called TMC1, one of more than 70 identified so far that can cause deafness upon mutation. The crucial role that this gene plays in hearing was identified a couple of years ago by lead study author Jeffrey Holt and his team from Harvard Medical School, ending a frustrating ongoing hunt. They discovered that it forms part of channels located on tiny sensory cells in the inner ear, which facilitate the conversion of sound vibrations into electrical signals. These impulses then travel along nerves to the brain, ultimately allowing us to perceive sound.

For the investigation, published in Science Translational Medicine, the researchers created two different strains of mice with genetic deafness involving TMC1. The first, in which the entire gene was deleted, was designed to model the recessive form of TMC1 deafness whereby young children experience hearing loss following the inheritance of two mutant copies of the gene. The second, in which they made a small tweak in the TMC1 code, represented the less common, dominant form of the gene, which causes children to go deaf during adolescence after a single faulty copy is inherited.

To correct these mutations, the researchers engineered a harmless virus commonly used in gene therapy, called adeno-associated virus 1, to possess a normal, healthy copy of either TMC1 or its relative TMC2. They also added in a DNA sequence called a promoter, which meant that the gene was only switched on, or expressed, in sensory cells located in the inner ear. Because the virus does not need to insert its genes into our own genome in order to be expressed, this alleviated the concern that it could disrupt native DNA, Holt told IFLScience.

After injecting the viruses into the inner ear, the researchers observed some remarkable effects. In the recessive models, not only did the sensory cells regain the ability to respond to sounds, but a portion of the brain involved in sound perception also began displaying activity. Ultimately, these responses allowed the animals to hear once again, which was confirmed by exposing them to noises and measuring their reactions. The researchers also saw positive effects in the dominant model in which a TMC2-containing virus was used, with function restored at both the cellular and systems level, but unfortunately it was somewhat less successful at the behavioral level.  


Although these early results are promising, the researchers need to continue to monitor the mice to see whether the restoration of hearing loss is sustained for longer than the already observed period of two months. They also plan to extend this work and investigate other forms of genetic deafness, including those which cause Usher Syndrome, Holt told IFLScience. This condition causes both blindness and deafness, so Holt thinks that it’s possible that a single gene therapy agent might help to treat both disorders, but there is still a lot of research and development before this approach is ready for the clinic.


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  • hearing,

  • genetic deafness,

  • TMC1,

  • TMC2,

  • hair cells