This is a Discovery Research Grant awarded to Professor Karen Steel at King’s College London in 2021.
Losing our hearing as we get older is very common, and can cause people to become disconnected from their family and friends and their day-to-day life.
There are currently no treatments that can reverse hearing loss or slow down its progression. Researchers around the world have been working to develop these treatments, including using gene therapy. However, as yet, no research has conclusively shown that it is possible to reverse hearing loss once the inner ear has matured.
The researchers will investigate whether it is possible to reverse a specific type of hearing loss in an adult ear. To do this, they’ll study mice which have a specific change in a gene called Pex3. As a result of this change, these mice develop progressive hearing loss. Changes in this gene cause severe hearing loss in children, and there is some evidence that it may also be involved in milder forms of hearing loss in adults. Pex3 is important for many normal cell functions, including how the cell deals with lipids (fats) and cellular stress. It’s found on small structures called peroxisomes within all cells. Peroxisomes are thought to be involved in the inner ear’s response to loud noise, protecting hair cells from damage.
The researchers will try to reverse the hearing loss in the Pex3 ‘mutant’ mice by correcting the gene and thus reactivating its function. They’ll also study whether there’s a time limit after which this reversal is no longer possible. This would suggest that there is a “critical period” after which it is no longer possible to improve hearing.
The researchers will look carefully at the connections, called synapses, between the sound-sensing hair cells and their associated auditory neurons (which carry sound information to the brain). They’ll do this because the main feature associated with hearing loss in the Pex3 mutant mice is loss of these connections. They’ll also investigate whether the Pex3 mutant mice are especially sensitive to noise damage.
If reactivating the Pex3 gene reverses hearing loss in these mice, this will show that hearing loss can be reversed even after the inner ear has fully developed. This will encourage the development of genetic treatments for hearing loss by providing proof that it is possible.