Gene therapy for deafness moves closer

A technique that delivers genes into the inner ears of mice has been used to restore hearing, marking the first time that gene therapy has been successfully used to treat deafness.

The study, published in Science Translational Medicine, focused on mice with deafness caused by the TMC1 gene. TMC1 is one of over 70 genes known to cause hereditary deafness, and accounts for four to eight percent of hereditary deafness cases in humans. When both copies are missing in humans, it results in profound hearing loss by around the age of two.

The technique harnesses the natural ability of viruses to transfer viral genes into cells. The scientists hijacked this ability to deliver genes into the sensory cells of the ear that transmit sound signals to the brain. Each virus was modified so that it carried a working copy of the TMC1 gene and was no longer infectious. The viruses were then injected into the inner ears of mice that were missing both copies of TMC1.

The scientists measured nerve signals between the ear and the brain, and found that these signals were restored following treatment with viruses carrying the TMC1 gene.

More importantly, the mice regained a normal response to loud noises following treatment, confirming that the nerves were working correctly. The mice were placed into a 'startle box', where sudden, loud sounds are emitted.

'Mice with TMC1 mutations will just sit there, but with gene therapy they jump as high as a normal mouse,' said Dr Jeffrey Holt of Boston Children's Hospital and Harvard Medical School, who led the study.

The researchers also tested the technique in mice who did have the TMC1 gene but a version with a mutation — a model for a condition in humans that causes deafness by around adolescence. In these mice, gene therapy with TMC2 — a gene closely related to TMC1 — resulted in measurable success at the cellular and brain level, but more modest efficacy in eliciting a startle response from the mice.

TMC1 and TMC2 both encode channels in the microvilli of the inner ear's sensory hair cells. In response to movement generated by sound waves, the channels open, which results in the generation of an electrical signal that ultimately travels to the brain. Because they play such a central role in hearing, when the genes are missing or defective, this leads to deafness.

In the future, the researchers hope the technique developed in this study can be used with other genes that cause hereditary deafness. Dr Holt said: 'I can envision patients with deafness having their genome sequenced and a tailored, precision-medicine treatment injected into their ears to restore hearing.'

Clinical trials are likely to be five to ten years down the line, with more work needed to translate the gene therapy technique into humans. However, there is optimism in the field with Professor Tobias Moser of the University Medical Center Gottingen telling Reuters: 'It's an exciting time for gene therapy in hearing.'