U.S. researchers report they've restored some hearing in mice with an inherited form of deafness by means of gene therapy, a finding that could lead to treatment of congenital deafness in people.
When faulty genes in the mice were replaced with working copies, the mice could sense and respond to sounds, the researchers said, raising hopes the same process could help people with hearing loss that results from genetic mutations.
"Our gene therapy protocol is not yet ready for clinical trials — we need to tweak it a bit more — but in the not-too-distant future we think it could be developed for therapeutic use in humans," says Jeffrey Holt, a professor of Otolaryngology at Harvard Medical School.
More than 70 different genes have been found to result in deafness if mutated, the researchers explain.
Holt, along with colleagues at Harvard and at the École Polytechnique Fédérale de Lausanne in Switzerland, worked on one of those genes, known as TMC1, a typical cause of deafness when its is missing or mutated.
TMC1 is responsible for encoding a protein important to hearing that helps convert sounds into electrical signals to be sent to the brain.
Gene therapy was conducted on two categories of mice with TMC1 mutations that are good models for similar mutations linked to deafness in humans.
One of the strains of mice is completely missing the gene, which makes them a good model for human recessive TMC1 mutations: Children with two mutated copies of the TMC1 gene tend to experience significant hearing loss at a very young age, as early as two years of age.
The other strain of mice possesses a specific mutation in the TMC1 gene that alters a single amino acid. In humans, a single instance of a similar mutation can lead to kids gradually losing their hearing starting between the ages of 10 to 15.
The researchers used an engineered virus to deliver healthy TMC1 genes into the inner ear of the mice.
In the mice missing the gene, the working genes restored the ability of sensory hair cells in the ear to respond to sound by producing measurable electrical currents, and they also restored activity in the portion of the brainstem involved in hearing.
In the mice with the mutated TMC1 gene, the working genes were effective at the same cellular and brain level, but in addition, were partially successful in restoring a level of actual hearing, the researchers reported in the journal Science Translations Medicine.
The viruses used to deliver the genes are safe and are already in use in other human gene therapies for blindness, heart disease, muscular dystrophy and other conditions, Holt noted.
"I can envision patients with deafness having their genome sequenced and a tailored, precision medicine treatment injected into their ears to restore hearing," he says.
