LL-341070 Remyelination

[frohike]

Great news if you are mouse!

A new study shows that a novel drug (LL-341070) helped repair damaged myelin in the visual system of mice. Myelin is the protective coating around nerve fibers, and damage to it is often implicated in tinnitus, especially noise-induced tinnitus.

What's particularly interesting about this study:

• The drug seemed to work better than existing treatments at promoting nerve repair.
• Even partial repair of the nerve was enough to see improvements in function.
• The treatment was effective even when the nerve damage was pretty significant.

Why it might be relevant to us (and why I'm sharing it)

Tinnitus is often linked to damage to the auditory nerve and the myelin coating. If we can figure out how to repair that damage, it could potentially lead to new treatments. While this study isn't directly about tinnitus, it helps us understand how nerves might be repaired, which is a crucial first step.

Important to keep in mind

• This is very early stage research.
• It's in mice, not humans. And what works in mice doesn't always translate to humans.
• It's in the visual system, not the auditory system.
• There's no guarantee this will lead to a tinnitus cure (or even treatment).

Anyway, this shows that nerve repair is possible, and that even partial repair can make a difference. It reinforces the idea that researchers are actively looking for ways to address nerve damage, which gives me a little glimmer of hope for the future.

Here's the link for any scientist out there:

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function

 

[Nick47]

@frohike, a good find. I firmly believe that tinnitus is generated and maintained peripherally, which then leads to altered cell activity in areas of the brain responsible for sound processing and sensory integration. It's the first domino that sets off the chain reaction.

But is this idea really that controversial? Since the observations on cochlear implants, at least four institutions are now working on treatments that target the auditory nerve peripherally.

That said, this does not mean it cannot be intercepted at the brain level. All lines of inquiry remain open.

 

[HighleyTall]

Interesting find.

Dr. Jack Pulec:

A cochlear nerve neuroma or any other cerebellopontine angle lesion pressing upon the cochlear nerve can discharge the nerve similarly to other forms of compression. The resultant erosion of myelin sheaths and the "crosstalk" between the cochlear efferent and afferent nerves can produce tinnitus.

Electron microscopicexamination of the excised segment of the right cochlear nerve revealed degenerative change consisting of a mild swelling and vacuolization of myelin sheaths.

Dr. Jack Pulec always sectioned a 5 millimeter segment of the cochlear nerve in his patients.

This case involved a patient who developed debilitating tinnitus after a barotrauma.

In the majority of his patients (101 total), sectioning the nerve, which he performed 151 times in his career, resulted in complete relief from tinnitus. Forty three experienced improvement, while only seven did not.

After decades of tinnitus and hyperacusis, I am confident that my condition is a peripheral nerve problem caused by sensory cells (see the work of Megan Beers Wood) running in overdrive, sending too much current through the power cables.

For the past few months, my tinnitus has not just been a noise. It has become a nerve pain with burning sensations, tingling on my skull and face, migraines... absolutely horrible.

 

[UKBloke]

It's in the visual system, not the auditory system.

This recent study on mice discusses links between neuropathic pain and hyperacusis. There's evidently quite a bit of research into the role myelination plays in neuropathic pain so it looks like the common denominators are there whether it's visual or auditory systems.

 

[Joeseph Stope]

So, the damage is (or is likely to be) in the hearing nerve rather than the cochlear hair cells?

All we need now is a kindhearted multibillionaire, preferably someone suffering from tinnitus, hearing loss, or a similar condition.

News like this, people thinking outside the box, cheers me up a bit.

 

[dd314]

I firmly believe that tinnitus is generated and maintained peripherally

I used to believe this but I'm not so sure anymore. There was a wildly successful tDCS study last year which gave people a -30 TFI score and I'm sure it entails actual volume reduction.

tDCS only affects the cortex, which is the outer layer of the brain; it doesn't even affect deeper structures like the DCN. Is it possible that central generation might be a maladaptation to lasting peripheral damage? Sure, but it's looking like the on/off switch is in the brain so I'd say it's both generated and maintained in the brain.

 

[HighleyTall]

So, the damage is (or is likely to be) in the hearing nerve rather than the cochlear hair cells?

All we need now is a kindhearted multibillionaire, preferably someone suffering from tinnitus, hearing loss, or a similar condition.

News like this, people thinking outside the box, cheers me up a bit.

Read the work of Dr. Megan Beers Wood. It is very interesting.

Hair cells and synapses are, of course, damaged too. But I actually believe that tinnitus and hyperacusis have the same underlying cause. Someone with mild tinnitus will likely have mild hyperacusis in a very small frequency range, though it may not be noticeable.

I developed mild tinnitus after noise trauma, and it took me some time to realize that I had mild hyperacusis as well. Restaurants started to bother me. Over the years, this developed into broadband hissing tinnitus along with very noticeable hyperacusis. Now, I have to live like a hermit.

If you develop an acoustic neuroma, you experience tinnitus because the nerve is compressed, likely damaging the myelin. This can cause tinnitus even with perfect hearing and intact inner and outer hair cells.

Researchers have spent far too long focusing on the brain without finding answers. I burned Jastreboff's book. In my opinion, he has caused more harm to patients and research than Dr. Joseph Goebbels.

 

[Nick47]

Is it possible that central generation might be a maladaptation to lasting peripheral damage?

This is only my hypothesis based on the available evidence. If tinnitus is generated or maintained by the brain, then I would assume that any peripheral treatment would not be able to modulate it.

The counterargument would be: why does not everyone with hearing damage develop tinnitus? I have noticed that sudden hearing loss or acute acoustic trauma is more likely to trigger tinnitus than gradual or age related hearing loss.

 

[Joeseph Stope]

This is only my hypothesis based on the available evidence. If tinnitus is generated or maintained by the brain, then I would assume that any peripheral treatment would not be able to modulate it.

The counterargument would be: why does not everyone with hearing damage develop tinnitus? I have noticed that sudden hearing loss or acute acoustic trauma is more likely to trigger tinnitus than gradual or age related hearing loss.

It seems that hearing research and tinnitus research are developing on a wide front, to borrow a phrase from military technology.

The Bionics Institute focuses on finding an objective way to detect and measure the volume of tinnitus, which could accelerate the pace of research and clinical trials.

Susan Shore is working on the brain side of things, using sound therapy along with additional stimulation.

This thread discusses myelin repair and its effect on nerve fibers.

And let's not forget about imaging technology. MRI and PET (positron emission tomography) might go through some new iterations once artificial intelligence is added to the mix.

Recent news about archaeologists deciphering 2,000 year old burned scrolls with imaging techniques and AI got me thinking.

If we are soon going to get updates on Cicero and Aristotle, then perhaps they could also turn their attention to what is happening in vivo with the stereocilia and connector synapses within the cochlea and auditory system.

And maybe I should mention Jastreboff, who focuses on the psychological side of things. He takes a lot of criticism on the forums.

 

[Ozhe]

Perhaps transcranial magnetic neurostimulation, which has been largely overlooked for tinnitus treatment, will be accepted as a clinical therapy with new application protocols that ensure both safety and efficacy.

 

[HighleyTall]

The counterargument would be: why does not everyone with hearing damage develop tinnitus? I have noticed that sudden hearing loss or acute acoustic trauma is more likely to trigger tinnitus than gradual or age related hearing loss.

Yes, like my father—a carpenter who worked all his life with loud machinery without any protection whatsoever. He was almost deaf at 88 but never experienced tinnitus or hyperacusis.

The difference is that I experienced a single but extreme noise trauma—it felt like a knife stabbing into my ear. And it seems that noise trauma isn't the only cause; barotrauma can trigger it too (see the study by Pulec).

Perhaps transcranial magnetic neurostimulation, which has been largely overlooked for tinnitus treatment, will be accepted as a clinical therapy with new application protocols that ensure both safety and efficacy.

They have to find the root cause of tinnitus first.

 

[Ozhe]

They have to find the root cause of tinnitus first.

Several functional imaging studies have shown that people with tinnitus exhibit abnormal activity in the auditory cortex and associated limbic regions of the brain. Because of this, the neural mechanisms of tinnitus make it a strong candidate for suppression using TMS.

In some respects, the evidence supporting the efficacy of rTMS for tinnitus is even stronger than the evidence for its use in treating depression. Yet, rTMS is widely accepted and used worldwide as a treatment for major depression.

Unresolved Issues Associated with Transcranial Magnetic Stimulation (TMS) Treatment of Chronic Tinnitus

 

[HighleyTall]

Imaging that shows abnormal activity in the brain does not prove anything. Damaged sensors or nerves could be responsible for the brain receiving incorrect or extreme input, which would then result in abnormal activity.

Dr. Pulec was highly respected and certainly not a charlatan. How do you explain these results?

There is no evidence that rTMS is effective for treating tinnitus.