Frequency Therapeutics — Hearing Loss Regeneration

Opinions and logic does not account as proof or evidence. We need a Galileo of hearing, not another Aristotle. With that said, Charles Liberman has definitely presented some very convincing hypothesis. He is one of the most prominent researchers in this field, and we need more people like him. We will know if these hypotheses are confirmed or not when we start collecting and analyzing data from clinical trials on humans.

We will also need new tools to make comparisons before and after therapy. Non-invasively! Simple audiograms will not be adequate. If we don't get these tools in time, we might as well start believing in magic! If the therapies work well, we will not know for sure why they work. At least I am of the opinion that seeing is believing!

 

What kind of hearing aid? You mean those that mask the tinnitus? Or those that amplify sounds? Can you give example of people who had their tinnitus diminished by using hearing aid? Also, did the effect last long after hearing aids were removed?

One way I can think of hearing aids improving tinnitus might be by improved frequency discrimination. This might be possible by increasing stimuli to hair cells adjacent to the damaged hair cells. But I doubt this would help much if the underlying cause of tinnitus is synaptopathy. Either way, this would hardly make a lasting effect when the hearing aids are removed. It would require the use of hearing aids all the time.

As long as there are no tools to assess cellular damage in the cochlea, non-invasively and in vivo, everyone is working under assumptions and in the blind. Including the hearing aids companies. They might have "advanced" hearing aids, but they don't quite know why they are working, if they are working.

I am strongly opposed to use of hearing aids. If they work for someone, that's fine, they should have it. But the very concept of hearing aids seems like violating the cochlea. It just doesn't speak to me. Cochlear implants are very different. These are in my opinion the only true remedy for hearing loss currently available in the field of hearing restoration. It's unfortunately only available to those with severe or profound hearing loss. Fortunately I should say! Because those with mild to moderate hearing loss should have a better chance of having their hearing restored by the new promise of regenerative medicine.

Simply put, the field of ear and hearing is almost entirely lacking medical treatments. There is very little that can be done here, even for problems of the middle ear. When you read about it you would think that inner ear problems are the only problems, and that they by now can treat everything else concerning the outer and middle ear. It's not true. It really is a field of unmet medical needs, especially for the inner ear, but not limited to the inner ear.

 

Wrong perception of lost sounds? How can there be any perception at all if the sounds are lost? Isn't that what we call tinnitus? Perception of sound without external source. It is not because we perceive these sounds the "wrong" way that we have tinnitus, it's because we do not perceive them at all, due to some damage in the cochlea.

How can you get back lost sounds/frequencies? Without treating the underlying cause, i.e. regenerating synapses and hair cells?

And hearing aids are not? Or is that because hearing aids don't do much at all for your hearing if you have a mild hearing loss so you don't notice the difference?

You don't lose frequencies, you lose synapses and hair cells. These synapses and hair cells correspond to certain sound frequencies. Hearing aids can't recover lost synapses and hair cells.

You can't amplify lost frequencies, that would mean making dead cells detect more of the sound. That's not how it works.

So you had T for 20 years? And you were able to manage it with hearing aids? But what happened in 2014? Why would anxiety cause T? I know I had anxiety right before I noticed for the first time that I had T. I think these anxiety episodes are precursors to tinnitus and they are due to recent synaptopathy or hair cell loss.

Can you still manage T with hearing aids?

 

The way hearing aids work is they amplify certain frequencies. If you have a cellular damage corresponding to 4500 Hz in the cochlea, amplifying that frequency alone will not help you hear that frequency better. If these cells are dead, they are dead. There is no way around that fact. Except regenerating them! But we are still not there yet.

What hearing aids do is they amplify sounds at 4400 Hz and 4600 Hz. Assuming that the cells surrounding the 4500 Hz region have survived, they will get extra stimulus and thereby increased signal strength. This is supposed to help the brain make up for the loss at 4500 Hz. The brain is supposedly smart enough to fill in the gap at 4500 Hz using the input from 4400 Hz and 4600 Hz. The way this might work is if the frequency band is wide enough at 4400 Hz and 4600 Hz so that the brain may differentially extrapolate the 4500 Hz sounds.

I doubt that it sounds anywhere near as good as having the sensory cells and synapses at 4500 Hz biologically restored. Also, if you have too many of these gaps in the cochlea or if they are too far apart, I don't think hearing aids will help you much. A deaf person for example has no use of hearing aids because there is nothing to amplify! No sensory cells!

That's one advanced brain! Brains are indeed very advanced, but I don't think hearing aids are good enough in the long run. Putting extra stress on surrounding cells can't be good for cell survival. We can do better! Much better! Especially now that we know so much more about ears and hearing! We should not be satisfied with this and allow the hearing aid companies to set the standards.

Companies like Frequency Therapeutics are seeking biological answers to the problem. But they are not only up against biology, but also the establishment. Hearing aid and cochlear implant is a billion dollar industry. These companies will not look kindly on anything that disrupts their cash flow. They will want to push back these new approaches to treating hearing loss and deafness so that they have enough time to further advance their own technology and stay competitive.

 

Yeah! I thought about you! It's hard to think that your T would disappear when you put ear muffs on. I think for most people it's the other way around.

I would say you can lose frequencies if the gaps between dead and healthy hair cells are too wide. How do you explain naturally occurring upper range frequency loss from 10000 Hz to 20000 Hz (Presbycusis)? Loss of sensitivity or loss of hair cells and synapses?

 

Thanks to healthy surrounding cells.

Due to loss of cells at that frequency or very close to it.

A 1000 Hz tone does not exclusively stimulate the 1000 Hz section of the cochlea. It rather stimulates a range of frequencies in the cochlea, perhaps from 900 Hz to 1100 Hz. You perceive this as a 1000 Hz tone, even if you have missing hair cells at exactly 1000 Hz. This is possible because the brain is smart enough to predict the highest peak to be at 1000 Hz by using the information from the surrounding hair cells. A 40 dB hearing level at 1000 Hz is like a mean average hearing level for frequencies ranging from 900 Hz to 1100 Hz, centered at 1000 Hz.

Well it's not binary. One reason is because outer hair cells are innervated by spiral ganglion neurons in bundles of 15 or more hair cells. For 1 neuron you have 15 outer hair cells. That's not binary (in the sense of one on one correspondence)! I am not even accounting for the inner hair cells. The second reason is the way that fluid/mechanical waves propagate inside the cochlea. This is all the more reason why the cochlea is such a complex organ.

There is no reason to believe that there is a one on one correspondence between test tone pitches and the cochlea. This is exactly why you don't see the graph zig zagging (unless you have severely damaged cochlea). The audiograms show mean average hearing levels at pitches one octave apart: 250, 500, 1000, 2000, 4000, 8000 (plus the half octave 6000) Hz. That's why we don't need to do the test with 1 Hz increments to get an idea of the hearing level. Such test would take at least two hours to complete, if not more. If you were to do such a tedious test you might see the kind of zigzag graph you describe.

Frequency ranges, yes. But also discrete frequencies, with the help of surrounding healthy cells within the range. In other words, if all your cells and synapses are dead at 1000 Hz, you will still be able to perceive 1000 Hz tones if your hair cells 100 Hz below and 100 Hz above that are healthy and alive. This way you can hear all the frequencies in the range 900 Hz to 1100 Hz. But you will have the classic "dip" at exactly 1000 Hz.

The "dip" is more or less evident on the graph, i.e. more or less shallow and sharp. The deeper and sharper the dip, the more severe the damage is at that test frequency. But this can be elusive. The dip can be shallow and dull. So it depends on the sampling of the test. You need more sampling frequencies and more sampling points to tell how far-spread the damage is at the cochlea. The standard hearing test consists of 7 sampling frequencies. You will need more than that. The standard hearing test is a good gauge for overall hearing level. But it cannot serve well as a way to assess this kind of granular hearing discrepancies and to give us detailed information about the cellular damage in the cochlea.

A visual tool, such as a µOCT endoscope would serve that purpose much better. Not to mention how much faster we could assess the damage, compared to doing insane 1 Hz increment audiometry. A visual instrument like that is something we are currently missing in the clinics.

The last point I want to make is that if the range at which you have cellular damage is wide enough, you will not be able to hear certain frequencies within that range, least of all the mid frequency. If the cells corresponding to the range 500 Hz to 1500 Hz are all dead, I bet you can't hear a 1000 Hz tone! As you get closer to the endpoints of that range you may start to hear some tones. So you may be able to hear the 800 Hz tone, as well as 1200 Hz tone, but maybe only after increasing the volume to 50 dB. At the very endpoints you would most certainly be able to hear the tones, assuming you don't have any other damaged segments below 500 Hz or above 1500 Hz. So you may hear the 500 Hz tone, perhaps at mild to moderate 30 dB level.

Not sure what to make of this... how or why what happens? I may have already answered this... if you're referring to why we still can hear certain frequencies at some level, even after damage to the hair cells or the synapses in a certain region of the cochlea.

 

Agreed!

Agreed!

What I mean here is that you might see a very different graph if you sample more than the standard 7 frequencies. You might see more than only one sharp rise and fall in the graph, i.e. zigzags. We get back to your binary analogy. (Never thought I would use the word binary and analogue in the same sentence.)

D'oh! Perfect fifth?!

Why do we even have that odd boll in there? All the other frequencies are one octave apart.

Fair point! But we can't know for sure until we test that. It would be interesting to see how that works out, just as an experiment.

Aha! So we are on the same page then?! And here I am wasting digital ink on trying to convince you in something you already agree on. Sorry! I completely misinterpreted you.

Funny how my smiles smack their heads in sync!

 

I just have to say I am surprised that so many of you were helped by using a hearing aid. Using hearing aids to boost hearing thresholds is one thing, but using them to effectively lower tinnitus is something I did not expect. This is a significant finding. It further strengthens the hypothesis that tinnitus is caused by loss of sensory cells and/or synapses.

But it also seems like those who previously found relief by using hearing aids are now faced with the problem that hearing aids no longer help them. Could this be because of new sensory/synaptic loss? How can hearing aids be reconfigured to make use of another set of healthy cells?

Of course, we can't just keep reconfiguring hearing aids and wearing down another set of healthy cells. We need to be able to bring new cells to life. This is of course something we all strive for. Hopefully this will all change when Frequency Therapeutics and other companies like it have a treatment ready!

 

It was about Frequency up until about 20 posts back. Then it derailed into hearing aids. So let's bring this train back on track.

What can you tell me about the delivery method that Frequency plans on using?

Do they make an incision in the tympanic membrane? Or they just push the needle through it? They release the molecules at the round window? Then what? How are these molecules taken up through the round window membrane? Several companies seem to plan on using this technique but I found no detailed explanation of how this works.

 

I think they will need to make an incision, because they probably need to see into the middle ear and aim for the round window. I don't think they can do that without putting in an endoscope through the tympanic membrane, along with the syringe.

The concept behind this delivery method is something called diffusion. The round window is semi-permeable which means it can allow molecules to pass through it. This is the way ototoxins get inside the cochlea too (amikacin).

 

I thought they needed a visual guide to facilitate contact with the round window. So it's enough to just tilt your head and the gel itself will facilitate contact with the round window? What is this gel made of? How effective is round window access? Can the drug reach out to all regions of the organ of Corti this way?

 

@Mricha37 What company would that be?

I have been reading about this today. Apparently, the way of using syringe injections through the tympanic membrane has been in use since the 1940s. I don't think anyone can have a patent on this. What they might have patent on is the gel, and of course the drug itself.

 

There is a company called Auritec Pharmaceuticals that focuses specifically on drug delivery mechanisms.

But they currently don't have anything for the inner ear. Which is understandable, since there are no drugs on the market for treating inner ear disorders. @Mricha37 The paragraph above supports this general idea that a company normally has a patent for not only the drug, but also for the delivery system. But in case of inner ear disorders, no one really holds a patent for the delivery system. There is not really much to it, there is not enough complexity to even call it a "system". I guess this is a good thing, because many companies can share the same method, instead of each of them having to reinvent the delivery method.