How Gene Therapy could Cure Deafness

Cochlear implants achieved a great success in the past. However, there is hope that patients suffering from hearing loss won’t need to be dependent on an electronic device soon. Several research groups aim at making the damaged inner ear recovered by itself thanks to gene therapy.

It took many years of research to identify the gene that is crucial for the formation of the mechanotransducer channel, responsible for our capacity to hear sounds. These channels are located on the tips of the hair cells in the inner ear.  When the hair is moved through vibrations, these channels are opened and an electric current can flow through them. Thereby, the vibration is translated into electrical signals, which is then interpretated as sound by the brain. When the mechanotransducer channels lack, the hearing doesn’t work anymore. And that’s what happens, when the crucial gene TMC1 is defective.

Gene therapy could provide a unique tool to compensate the faulty gene in deaf children. Researchers at Boston Children’s Hospital, Harvard Medical School and École polytechnique fédérale de Lausanne could replace the defective TMC1 gene in mice to cure an inherited form of deafness.

Working copies of the defected TMC1-gene were introduced to the inner ear of mice, carried by adeno-associated viruses. These are considered safe for humans since they neither have the potential to cause cancer nor trigger a wide immune response. After several applications, the previously deaf mice showed a reaction to loud noise and the investigators could measure belonging electrical signals in the brain. These are outstanding manifestations of the impact of the treatment.

Credit: H. McDonald/Science Translational Medicine

Certainly, the drug is still premature and it would take several years to enable application in humans. However, the question if these results can be applied to human is not the main concern of the investigators. Mutated TMC1 is responsible for approximately 4 to 8% of inherited deafness cases. There are further 70 different genes that can lead to severe hearing loss.

“If you think how much it will cost to really go through all the clinical trials until you actually have [Food and Drug Administration] approval, this will I fear really limit the chances to put this into practice,” said Dr. Tobias Moser, a professor of auditory neuroscience at the University of Göttingen in Germany, via npr.

With the revolution of genome sequencing, its not unthinkable to sequence the genome of deaf babys and identify the defective gene. But will we be able to provide customized treatment?

Chances may be not as bad as it sounds. The group isn’t the first to try restoring the ear’s natural auditory mechanics through gene therapy. Hearing loss is often caused by damaged hair cells of the inner ear. This can happen through noise exposure or medical treatments. Novartis developed the drug CGF166, a recombinant adenovirus that delivers copies of a gene into the ear, which leads to the formation of new sensory hair cells. After proven efficassy in animals, the FDA approved the start of Phase I in the US. Therefore, Novartis is currently recruiting adults with hearing loss due to injured inner hair cells.

Not only the money needed for the trials, but also the costs of the potential therapy must be considered. The first gene therapy on the market, developed by uniQure, costed €1,1M! If this treatment move forward, let’s hope for the patients that the price will not be as high.

Anyway, and even if both previously described projects remain in an early stage, gene therapy could be a new hope on the horizon for the 360 million people affected by hearing impairment worldwide!