An Antibody to RGMa Promotes Regeneration of Cochlear Synapses After Noise Exposure

Abstract
Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

Hidden hearing loss results in compromised ability to understand words in a noisy background and has been implicated in tinnitus and hyperacusis. Further development of a treatment is therefore warranted and will require studies to determine optimal dosing after synaptopathic noise exposure either as a discrete event or a lifetime of smaller insults.

https://www.nature.com/articles/s41598-021-81294-5

 

Interesting!

I think ENTs should start doing a more comprehensive battery of tests to assess hearing performance. The old audiograms are totally outdated, not subtle at all, and cannot identify speech recognition problems.

 

The problems with audiograms are actually absolutely understated too. There have been recent examples of the audiogram being the sole measure that both audis and doctors use for determining things, despite there being countless examples of how flawed this is.

It is exactly why it isn't in any way considered best practice by the better audiologists to look solely at the audiogram any longer but rather the sentence recognition and word recognition scores are considered the ultimate measures presently. Pretty much this is why some people do so well with hearing aids for what is considered a mild moderate hearing loss for example and others do so badly with them and need the Cochlear Implant instead.

It is suggested that if your Audiologist/ENT solely looks at an audiogram as the measure of your hearing and nothing else then you should go elsewhere immediately. It is not going to lead to a positive outcome...

 

Yes, I know.

The problem is hearing issues are hard to fix, or impossible to fix, as hearing aids cannot improve sound and speech recognition in the same way that glasses fix vision problems.

 

Correct, which is why an implant is seen by many as being vastly superior to pretty much all hearing aids. As a result the only way improvement could be obtained is by cell/synapse regrowth.

 

The audiologist I went to was part of a chain of audiologists. These past few years they changed their attitude to tinnitus dramatically.

They now actively call up former customers with tinnitus to come in and do more tests with new equipment and the audiologists there were better trained to help people with tinnitus... even if simply guiding them towards CBT or relaxation techniques. (Something my original ENT did not do, she just said there’s nothing I can do).

Anyway, I went back and they now do:

Hearing test up to 16 kHz
Speech in noise test
Loudness perception test

This chain of audiologists also works together with the University Hospital of Antwerp. They even have one IN the hospital! I assume they share their data with the hospital for research purposes.

This is in Belgium btw.

 

That's all good news. It seems things are evolving and getting better.

By the way, I love Antwerp. Really nice city!

 

Belgian doctors do seem to take tinnitus and hyperacusis more serious than those in other countries.

 

What strikes me is that audiologists are jumping in the gap. They seem eager to take the role that many ENTs / doctors seem to neglect.

Of course, in the end, some forms of tinnitus can be mitigated with hearing aids, so that is an incentive. But still... a good evolution imho.

 

This makes Belgium out to be a nice place for finding a fix for tinnitus.

 

Another potential synaptopathy drug on top of OTO-413 and PIPE-505.

Good news.