Using gene therapy, a team of researchers for the first time successfully restored normal hearing to mice born deaf due to a missing protein, according to a study published today in the journal Neuron. This finding could be music to the ears of people whose congenital hearing loss is caused by genetic mutations that may prevent tiny inner ear hairs from interacting with neurotransmitters that are necessary for hearing. In the current experiment, mice recovered full hearing for an average of seven weeks, with two of 19 mice maintaining it for as long as one and a half years. “I was completely shocked,” says lead author Lawrence Lustig, director of the Douglas Grant Cochlear Implant Center at the University of California, San Francisco. “The hearing looked almost completely normal and you couldn’t tell these were rescued mice.”
Richard Smith, a geneticist at Iowa State University in Iowa City who was not involved in the study, says that the findings offer hope for the estimated 12,000 infants, or 0.3 % of all babies born each year in the US, with severe-to-moderate hearing loss in one or both ears. “A hearing aid or cochlear implant doesn’t correct hearing in the same way that eyeglasses correct sight,” Smith explains. “Those devices only aid in hearing—hence the need for alternative treatments.”
Previous studies have introduced genes that cause deafness into mice and then applied gene therapy to remedy the problem, thereby using an artificial congenital hearing loss animal model. By comparison, the current study tested the approach using mice born without the Vglut3 mouse gene—which produces the protein known as vesicular glutamate transporter-3 (VGLUT3). Without this protein, the inner ear cells could not release the neurotransmitter glutamate, which carries sound signals to the brain. The researchers injected a harmless virus called adeno-associated virus type 1 (AAV1), which carried a working copy of Vglut3, into the ears of some animals one day after birth and in others almost two weeks post-delivery. They confirmed that both groups of treated mice could hear based on electrical signals picked up by electrodes attached to the scalp during an auditory brainstem response test. During that test, inner ear hairs send signals through the auditory pathway which goes through the brainstem. The control group of mice with this mutation received no injections and showed no response on hearing tests.
Lustig believes his study is a big step towards clinical trials—possibly in as soon as five years—to test gene therapy for congenital hearing loss in humans. But there’s one potential drawback to the study: the mouse gene Lustig used does not correlate with the same behavior of the mutant human gene SLC17A8. While a mutation in this gene in humans causes high-frequency hearing loss in adulthood, no studies have linked it yet to congenital deafness in people.
The researchers used the Vglut3 gene because they already had these knockout mice available in their lab. Smith says the choice was understandable and doesn’t take away from the significance of the study. “Gene therapy is complicated and very expensive and so you want to choose a model you have on hand already,” he adds.
Today’s study comes on the heels of a recommendation from a committee within the European Medical Agency to approve a gene therapy for people who lack an enzyme that breaks down fat in the body. Other companies, such as GenVec and Novartis, which are mentioned in earlier Nature Medicine coverage on hearing loss, continue to work on gene therapy that seeks to repair sensory hair cells in the inner ear.
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