A gene therapy cure for inherited deafness has been successfully tested and could be offered to patients in under five years.
Researchers restored the hearing of deaf mice by injecting a virus carrying the healthy gene into their inner ears.
The research offers new hope to children born with defective genes that cause “profound” hearing loss, leaving them with a permanent handicap which may affect their education and employment prospects.
Lead scientist Dr Jeffrey Holt, from Boston Children’s Hospital in the US, said: “I can envision patients with deafness having their genome sequenced and a tailored, precision medicine treatment injected into their ears to restore hearing.”
The team hopes to start clinical trials of the therapy “within five to 10 years”, he said.
More than 70 different defective genes are known to result in deafness. The scientists focused on one, TMC1, which accounts for between 4% and 8% of cases and plays a central role in hearing by coding for vital inner ear protein.
The treatment was tested on two strains of mutant mouse representing different forms of TMC1-related deafness in humans.
One had no functioning TMC1 gene. Children with this kind of “recessive” genetic defect go profoundly deaf from a very young age, usually around two years.
The other mouse strain, called “Beethoven”, had a less common form of TMC1 deafness caused by only one copy of the paired genes not working. This “dominant” defect causes children to go deaf gradually from about the age of 10 to 15.
Deaf mice with the recessive defect fully regained their ability to hear after treatment with the TMC1 gene.
Placed in a “startle box” and exposed to abrupt, loud noises, they responded in the same way as healthy mice with no hearing problems.
“Mice with TMC1 mutations will just sit there, but with gene therapy they jump as high as a normal mouse,” said Dr Holt.
Mice in the “dominant” group were treated with a related gene, TMC2. Their hearing was partially restored, and the treatment was successful at the cellular and brain level.
Both TMC1 and TMC2 code for proteins at the tip of sensory hairs in the inner ear that, when stimulated, convert sound vibrations into nerve signals.
A defective TMC1 gene is enough to cause deafness on its own, but the scientists showed that gene therapy with TMC2 could compensate for its loss.
An engineered virus called adeno-associated virus 1, or AAV1, was used to insert the corrective genes. A genetic switch sequence known as a “promoter” was also used to ensure the genes were only activated in the inner ear hair cells.
The research is reported in the journal Science Translational Medicine.
Dr Holt said: “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.”
He added that other forms of genetic deafness may also respond to the same kind of treatment. Overall, severe to profound hearing loss in both ears affects one to three children in every 1,000 born.