Longevity Briefs: Could We Reverse Hearing Loss With Gene Therapy?

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Decline in hearing ability seems to be an inevitable part of ageing, though minimising exposure to loud noises may slow that decline down. Hearing loss happens partly because of the death of hair cells, the receptor cells within the inner ear that convert vibrations into electrical signals. However, the nerves linking these cells to the brain also change with age. In particular, a group of inhibitory neurons are rewired to connect directly to the hair cells and inhibit their output.

Interestingly, this wiring setup exists temporarily in embryonic mammals before they have developed the ability to hear, and can be replicated by deleting a gene called Myo7a. Myo7a codes for a protein that is important for converting vibrations into electrical signals, and variants of Myo7a can cause various forms of deafness in animals and humans alike. Since Myo7a is also downregulated in ageing humans, researchers in this study wanted to see if there was potential to target it to reverse hearing loss.

The discovery:

The researchers first developed a genetically engineered mouse model in which Myo7a would be downregulated after birth. As expected, the mice progressively lost their hearing and became almost completely deaf within a few weeks, and their neurons showed rewiring as described. They then gave the mice an adeno-associated virus containing DNA coding for Myo7a in order to restore levels of the protein. They found that mice given this Myo7a gene therapy had their hearing partially restored, though their hearing was still a lot worse than that of normal mice. It also partially restored normal wiring between the hair cells and brain.

Graph showing level of noise necessary to produce an auditory brainstem response (ABR) at different sound frequencies in normal mice (black), Myo7a downregulated mice (red) and Myo7a downregulated mice treated with gene therapy (blue).
*In vivo AAV9-Myo7a gene rescue restores hearing and cholinergic efferent innervation in inner hair cells*

Keep in mind that the decibel scale is logarithmic, so 50 decibels (about as loud as rain) is a lot quieter than 100 decibels (about as loud as a helicopter). So the treated mice were still only able to hear loud noises, though this is obviously still significantly better than near-total deafness.

The implications:

This study shows that the rewiring that occurs when Myo7a is deactivated can be reversed with gene therapy to restore hearing, which means that the same could be possible in old age. We’ll need more studies to confirm that, since the hearing loss that was restored in this study was specifically caused by Myo7a downregulation. Age-related hearing loss is more complex than just the downregulation of a single gene, and so a similar treatment might not have the same effect, but could hopefully become part of wider hearing loss treatment.