Hearing loss is a pretty common affliction as people age, especially those who have been exposed to sustained loud noise throughout their lives. But now, biologists at the Universities of Washington and Iowa are testing drugs they call “chemical earmuffs” in mice, which could prevent hearing loss without affecting the volume or quality of sound.
Synaptopathy is a form of hearing impairment or even deafness caused by prolonged exposure to loud noises throughout life. When the inner ear hair cells pick up vibrations from sound waves, they release a chemical called glutamate across a synapse to receptor cells that then transmit the signal through nerves to the brain. But if the noise is too loud for too long, the cells can produce too much glutamate, which over time prevents the receptors from working, resulting in hearing loss.
But the researchers on the new study discovered a previously-unknown mechanism at work and, more importantly, how to take advantage of it to prevent hearing loss in the first place. The receptors are known to have a protein called GluA2, but the team found that some don’t – and interestingly, the ones that lack GluA2 are the ones that succumb to synaptopathy.
On closer inspection, they found that the GluA2-lacking receptors tend to allow calcium ions to pass into the inner-ear neurons, where they cause damage. So, they investigated whether these vulnerable receptors could be a drug target.
In experiments with mice, the researchers showed that a drug called IEM-1460 can effectively block receptors that are missing GluA2. That effectively prevents synaptopathy from taking hold, and the remaining receptors are sufficient to maintain hearing.
"What we found is if you block the GluA2-lacking receptors, a.k.a. calcium-permeable receptors, then you can prevent the damage, and the mouse can hear just fine because it still has the GluA2-containing receptors that can mediate synaptic transmission," says Steven Green, corresponding author of the study. "Now, we have a drug that doesn't prevent hearing, but does prevent hearing damage.”
The drug has so far only been tested in mice, so as usual there’s no guarantee this will apply to humans or ever make it to market. But the team is hopeful that this new understanding could lead to future treatments.
It would need to get less invasive, though – in these tests, the team surgically administered the drug directly into the cochleas of the mice, but that’s a bit much for human use. Ideally, the team says that similarly-acting drugs could be injected in people before they’re exposed to loud sounds to prevent hearing damage. Until then, of course, it’s best to avoid loud or prolonged noise exposure.
“Permanent hearing damage can be caused by noise levels that have been considered 'safe,' and people need to be careful about noise exposure because we can't yet repair synapses or regenerate hair cells,” says Green. “Our chemical earmuffs are, currently, just an indication of the direction research can go, not yet a proven, safe means of protection in humans.”
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: University of Iowa via MedicalXpress