Are faulty mitochondria to blame for hereditary hearing loss?

No fewer than 95 genes have so far been implicated in hearing loss. A new study into mitochondrial activity may open new and exciting avenues of research into potential gene therapies.
[DNA Strands]
Mitochondrial DNA are linked to premature hearing loss in a new genetic study.

Hearing loss affects an astonishing 15% of Americans over the age of 18. The potential causes of diminished hearing are varied; ranging from physical damage to infection.

Over the last few years, the role of genetics in hearing loss has been brought to center stage. State of the art genetic research steadily increases our understanding of how faulty genes can induce deafness.

Recent research published in The American Journal of Pathology looks at the role of mitochondrial dysfunction in a type of hereditary deafness that worsens over time and leads to profound hearing loss.

Lead investigator Gerald S. Shadel, PhD, and his team at the Departments of Pathology and Genetics at Yale School of Medicine conducted research on a genetically modified strain of mice.

Genetically modified mice

The mice were modified to overproduce a gene that codes for transcription factor B1, mitochondrial (TFB1M). TFB1M plays an important role in mitochondrial gene expression and has already been implicated in hereditary hearing loss.

These modified mice, known simply as Tg-mtTFB1 mice, have been shown to develop hearing loss at a much swifter rate than their unmodified counterparts.

Shadel and his team investigated the hearing pathways of the Tg-mtTFB1 mice and found a number of tell-tale modifications that seem to cause the inevitable worsening of the animal’s hearing.

The team noticed specific changes in the auditory system, particularly in the spiral ganglion nerves and the stria vascularis:

“We propose that the defects we observed in the stria, spiral ganglion neurons, and outer hair cells conspire to produce the observed hearing loss profile in Tg-mtTFB1 mice.”

The spiral ganglion nerves link the ear’s sound translating device – the cochlea – to the central nervous system via the auditory nerve. They have been described as “the initial bridge between the physical world of sound and perception of that sound.”

The stria vascularis is an area that is thought to produce the fluid of the inner ear – the endolymph. This fluid conducts sound information to receptor cells in the inner ear.

These two sections of the ear, if damaged, severely reduce the individual’s ability to hear.

Potential mitochondrial mechanism

Shadel and his team have managed to tease apart a potential mechanism that mitochondria might play in their premature demise.

The researchers theorized that the break down of the spiral ganglion nerves and the stria vascularis in Tg-mtTFB1 mice might be mediated by mitochondrial reactive oxygen species (ROS). ROS are natural byproducts of mitochondria’s activity and appear to stimulate the enzyme AMPK (an enzyme that modulates mitochondrial activity).

To investigate whether AMPK might truly be the villain, they dampened the activity of the enzyme. They did this by breeding a new strain of Tg-mtTFB1 mice with a limited ability to produce enzyme AMPK.

When comparing the hearing ability of the two Tg-mtTFB1 strains, they found that those with minimal AMPK were indistinguishable from standard mice. In other words, if AMPK was taken out of the equation, hearing was left wholly intact.

Shadel says:

“We conclude that reducing AMPK signaling has no effect on normal hearing at the ages tested but rescues or delays premature hearing loss in Tg-mtTFB1 mitochondrial deafness model mice.

This opens the possibility for intervention in humans based on inhibiting AMPK, which is already a drug target for several diseases.”

Although this study still leaves us a long walk from finally preventing hereditary hearing loss, it is a welcome new arrow in the quiver. There are an ever growing number of potential genetic targets to investigate, each with their own complex web of interaction.

Recently, Medical News Today reported on another study into a gene therapy that restored hearing in mice.

Written by Tim Newman

Be the first to comment

Leave a Reply

Your email address will not be published.