New gene therapy research to treat genetic deafness …

Posted: August 2, 2015 at 8:47 pm

Posted on: Friday, July 31, 2015 by Nicola Robas

We are a step closer to being able to prevent some types of inherited deafness thanks to ground breaking research showing that gene therapy has been successfully used in mice to restore hearing. Nicola Robas from our Biomedical Research team tells us more.

The instructions for how our bodies develop and function are contained in our genes. We each have small variations in our genetic instructions but most of the time these differences do not alter how a gene functions. However, sometimes the differences can stop a gene from working properly. If this occurs in a gene needed for hearing it can lead to deafness (known as genetic or inherited deafness). So far scientists have identified over 100 genes that can cause genetic hearing loss. While our ability to diagnose genetic hearing loss has vastly improved, the current treatments remain limited to hearing aids and cochlear implants. These devices can be very effective at improving hearing but they cannot help everyone with inherited deafness, and they do not fix the root cause of the hearing loss.

Researchers have been looking at one particular type of inherited hearing loss caused by changes in a gene called TMC1. The protein produced by the TMC1 gene forms part of the machinery in the sound-sensing hair cells of the inner ear that converts mechanical sound waves into electrical signals that are then sent to the brain, allowing us to perceive sound. If TMC1 is not working correctly, then sound signals cannot be sent from the ear to the brain, leading to a hearing loss. In people, changes in TMC1 can cause 2 forms of deafness. In the most common form of TMC1-related deafness, children become profoundly deaf from a very young age, usually around two years old. The second causes children to go deaf gradually from about the age of 10 to 15.

Gene therapy to replace a faulty gene with a normally functioning copy has the potential to prevent certain types of genetic deafness. New research, led by scientists at Harvard Medical School, has shown in mice, that gene therapy can restore the hearing of animals with a faulty TMC1 gene. A virus engineered to produce a healthy copy of this gene was injected into the cochlea of mice in which TMC1 wasnt working correctly (thereby acting as an experimental model of the human form of deafness).

25 days after the injection the mice showed a partial recovery of hearing. The mice went from having a profound hearing loss to a point where, if they were people, they would benefit from a hearing aid. The researchers think that only a partial recovery was seen because the virus delivering the gene was not able to reach all the cells it needed to. There are two types of sound-sensing hair cells in the ear - inner hair cells that activate the auditory nerves carrying sound signals to the brain, and outer hair cells that amplify sound vibrations allowing people to hear really quiet sounds. TMC1 is needed by both cell types, but the virus was only able to get into and rescue the inner hair cells.

At least half of all childhood deafness is inherited and we know there are more than 100 different genes that can cause deafness. If shown to work in people, then this gene therapy has the potential to cure one specific type of genetic deafness (TMC1-related deafness). TMC1 accounts for around 6% of genetic deafness so, if this approach is successful, it will only have a direct benefit for a small number of families. However, more people could benefit in the future as the same technology could be adapted to treat other types of inherited deafness just delivering a healthy copy of a different gene. The only problem is that many forms of inherited deafness affect the ear before birth so in these cases, a childs ear would need to be treated during pregnancy which, with the technology and surgical techniques available today, would be very difficult. So for now, gene therapy to replace faulty genes is likely to be limited to treating progressive forms of inherited deafness that start after birth.

At the moment, this gene therapy is not yet ready to be tested in people. More work still needs to be done in the laboratory to refine the techniques, improve the way the virus delivers the healthy gene, understand how long the effect lasts for, and gather enough data to deem the approach safe and effective. If all goes well, the researchers hope to begin clinical trials in people in 5 years.

This research was published in the journal Science Translational Medicine

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