Gene Therapy Cures Deaf Mice, Offers Hope Of Treatment For Congenital

“This is a welcome discovery that will hopefully lead to a greater range of options for families with deaf children and help reduce the impact of deafness for the child”. In this confocal microscopy image, microvilli are shown in red and cell bodies in green.

The team hopes to start clinical trials of the therapy “within five to 10 years”, he said.

The big question now is not whether gene therapy for inherited deafness will work, but whether there will be enough money to pay for it, says Moser.

More than 70 different genes have been found to result in deafness if mutated, the researchers explain.

TMC1 is responsible for encoding a protein important to hearing that helps convert sounds into electrical signals to be sent to the brain.

Jeffrey Holt of Boston Children’s Hospital and Harvard Medical School said that their gene therapy protocol wasn’t ready yet for clinical trials as they needed to tweak it a bit more but in the not-too-distant future he thinks it could be developed for therapeutic use in humans. This “dominant” defect causes children to go deaf gradually from about the age of 10 to 15. Within a month, around half the mice with one mutation showed brainwave activity consistent with hearing and jumped when exposed to loud noises.

Electrical signals in the brain confirmed that the mice were no longer deaf.

Their idea was to use gene therapy to replace mutated TMC1 genes with genes that functioned correctly.

“Current therapies for profound hearing loss like that caused by the recessive form of TMC1 are hearing aids, which often don’t work very well, and cochlear implants”, says Margaret Kenna, MD, MPH, a specialist in genetic hearing loss at Boston Children’s Hospital who is familiar with the work.

“Mice with TMC1 mutations will just sit there, but with gene therapy they jump as high as a normal mouse”, said Dr Holt.

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. 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 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.

“Once we realized we had this deafness gene we began thinking about how we might be able to restore function in these patients with genetic hearing loss”, Holt says. The scientists believe a range of other genes involved in congenital deafness could be treated by the same approach to treat the severe and profound hearing loss affecting between 1 and 3 of every 1,000 live births.

The TMC1 gene, along with an associated gene called TMC2, codes for a protein that is made in the tip of the tiny, hair-like projection or “microvilli” of the inner ear. “Anything that could stabilise or improve native hearing at an early age is really exciting and would give a huge boost to a child’s ability to learn and use spoken language”.

To tackle the problem, Holt and his colleagues equipped a harmless virus called adeno-associated virus 1 with corrected copies of the faulty gene.

“This is a great example of how the basic science can lead to clinical therapies”, says Holt.

The team focused on a gene called TMC1, which is a common cause of human genetic deafness. The results are testament to the vast dedication of the research team and their commitment to bringing best-in-class science ever closer to real-world application.