Despite the fact that genetic hearing loss can be linked to at least 100 different genes, just one single gene, STRC, can be linked to up to 16 percent of cases. Now, a new kind of gene therapy could help to reverse severe hearing loss linked to this gene.
A first-of-its kind gene therapy has been developed at the Boston Children’s Hospital. In a study, researchers successfully replaced the mutated protein, stereocilin, in the inner-ear of mice. This reversed severe hearing loss and in some cases, returning it to completely normal levels of hearing.
While tests on mice proved successful, the team behind the study will need to see if the technique works with the human stereocilin gene. This will first be done with inner-ear cells in a Petri dish taken from patients with STRC hearing loss. If this is successful, the team can then apply to the US Food and Drug Administration (FDA) for permission to begin human testing.
The stereocilin protein plays a small but integral part in our hearing. For us to be able to hear sounds, hair cells in the inner ear need to make contact with the ear’s tectorial membrane (tissue that plays a role in transforming sound to stimulation), vibrating in response to sound and converting these vibrations into signals to send to our brain. Stereocilin acts like a support, helping the hair cells stand up in a neat, organised bundle so the tips can touch the membrane.
If stereocilin is mutated, you don’t have that contact, so the hair cells are not stimulated properly”, said Jeffrey Holt, a scientist at the Boston Children’s Hospital and the study’s senior investigator.
“Importantly, the hair cells still remain functional, so they are receptive to the gene therapy. We think this will provide a broad window of opportunity for treatment – from babies to adults with hearing loss.”
In order to deliver the healthy stereocilin gene into the hair cells of the mice, the team used a synthetic adeno-associated virus (AAV). AAV only causes mild immune responses and is a preditctable virus, so it is quickly becoming a popular tool in modern gene therapy.
The team did face a problem with this approach. “The challenge we faced was that the gene for stereocilin is too big to fit into the gene therapy vector,” Holt said. To get around this, the study’s first author Olga Shubina-Oleinik came up with the solution of splitting the gene in two and putting the two halves into separate viruses in a recombination of the proteins.
To check the hearing of the mice, the researchers used two different tests. The first was similar to hearing tests used on babies, and the second monitored brain steam responses to different sound frequencies using electrodes on the scalp.
On testing, the mice were more sensitive to subtle sounds and had an increased ability to amplify soft sounds, tamp down the response to loud sounds and discriminate among different frequencies.
Holt and his team have now filed a patent application for this gene therapy technology. “It turns out that STRC gene variations are more common than we thought, which makes gene therapy for this disorder so important,” said Eliot Shearer, a co-author of the study.
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