Frequency Therapeutics — Hearing Loss Regeneration

[Lucifer]

Does anyone know whether Frequency have started accepting new participants for the clinical trial yet and have started dosing them? October is in 4 months time, hopefully results don't get delayed.

 

[Christiaan]

Per the researcher I corresponded with (and I have since spent a lot of time reading papers on this..."flat epithelia cochlea" on PubMed, Google Scholar and PubMed turns up a lot if you want a place to start), once you have lost all of your IHCs, and OHCs in a particular area of your cochlea, the support cells die and are replaced with flat epithelia. This seems to only happen with *total* losses and your audiogram will reflect that as a greater than 90 dB loss (from anything but the sub 250 Hz tones, where a more moderate audiogram change may reflect full loss).

If hearing loss isn't your main problem and tinnitus is, it only matters where your tinnitus is. I.e. if you have profound loss at 16000 Hz but then you have a moderate notch at 8000 Hz but your tinnitus is at 8000 Hz, then that's what is relevant for you.

That's a tricky thing @FGG. For some of us who have lower frequency loss <250 Hz and tinnitus on that same level, how can we know or test the extend of our dB loss? A standard audiogram doesn't cover this area, unfortunately, so is there another way to gain insight in lower frequency dB loss?

 

[FGG]

That's a tricky thing @FGG. For some of us who have lower frequency loss <250 Hz and tinnitus on that same level, how can we know or test the extend of our dB loss? A standard audiogram doesn't cover this area, unfortunately, so is there another way to gain insight in lower frequency dB loss?

You can get an extended audiogram that includes 125 Hz. Below that, you kind of have to infer it I think by what you can and can't hear and at what volume.

 

[GlennS]

the support cells die and are replaced with flat epithelia. This seems to only happen with *total* losses and your audiogram will reflect that as a greater than 90 dB loss (from anything but the sub 250 Hz tones, where a more moderate audiogram change may reflect full loss).

That doesn't sound encouraging to me. Consider that rarely if ever does anyone maintain their hearing all the way to 20 kHz. If that coincides with the tinnitus frequencies then you're screwed. I haven't done an extended audiogram but my hearing seems to drop off completely in my left ear at around 12 kHz and that is probably around the range of my most annoying tinnitus frequencies.

 

[FGG]

That doesn't sound encouraging to me. Consider that rarely if ever does anyone maintain their hearing all the way to 20 kHz. If that coincides with the tinnitus frequencies then you're screwed. I haven't done an extended audiogram but my hearing seems to drop off completely in my left ear at around 12 kHz and that is probably around the range of my most annoying tinnitus frequencies.

Mine drops off completely around that range too but I only have "severe" loss there. But apart from an audiogram both, I can't hear it at all. I'm more worried about my low frequencies.

Definitely get an extended audiogram.

 

[Flyingsheep]

That doesn't sound encouraging to me. Consider that rarely if ever does anyone maintain their hearing all the way to 20 kHz. If that coincides with the tinnitus frequencies then you're screwed. I haven't done an extended audiogram but my hearing seems to drop off completely in my left ear at around 12 kHz and that is probably around the range of my most annoying tinnitus frequencies.

Unless you're a rare case like me who tends to experience severely loud 15kHz ringing, despite the fact I can easily hear all the way up to about 18kHz without cranking the volume, and 19kHz has to be cranked to hear it. I don't think HF tinnitus is always related to HF hearing loss.

 

[AtlasFainted]

Mine drops off completely around that range too but I only have "severe" loss there. But apart from an audiogram both, I can't hear it at all. I'm more worried about my low frequencies.

Definitely get an extended audiogram.

I don't doubt you, but I've read reports on Tinnitus Talk of people actually getting tinnitus/hearing damage from the audiograms themselves.

My plan as of now is to hold off on the extended audiogram until FX-322 is released, in an effort to keep what little I have left from being obliterated while there is still nothing to bring it back before the support cells die off.

In the meantime I'll consult with someone who conducts extended audiograms on a regular basis just to get a clearer idea of what my odds are of not having profound loss.

 

[DoNotGoGentle]

Please explain how do they get FX-322 to repair hair cells in the right place where the damage is?

Maybe I was thinking about this because the progenitor cells and support cells in those areas will be exposed. So they can turn them on.

Thanks.

 

[FGG]

Please explain how do they get FX-322 to repair hair cells in the right place where the damage is?

Maybe I was thinking about this because the progenitor cells and support cells in those areas will be exposed. So they can turn them on.

Thanks.

I imagine it's similar to the intestines where cells signal to each other not to overgrow (would be neoplastic otherwise) so if there are healthy cells with the right signaling capabilities, it would not regrow there. Same way your skin cells only divide around a cut.

 

[FGG]

I don't doubt you, but I've read reports on Tinnitus Talk of people actually getting tinnitus/hearing damage from the audiograms themselves.

My plan as of now is to hold off on the extended audiogram until FX-322 is released, in an effort to keep what little I have left from being obliterated while there is still nothing to bring it back before the support cells die off.

In the meantime I'll consult with someone who conducts extended audiograms on a regular basis just to get a clearer idea of what my odds are of not having profound loss.

Let us know what they say! If there is a way to do this at home, that would be good for many people.

 

[GlennS]

Mine drops off completely around that range too but I only have "severe" loss there. But apart from an audiogram both, I can't hear it at all. I'm more worried about my low frequencies.
Definitely get an extended audiogram.

What's suspicious to me is the stereo aspect, where it's a mono signal in the YouTube clip and yet my perception of it fades off in my left ear as the frequency goes up but not my right. I also know that certain sounds like birds chirping or rain are much harder to hear just through my left ear. When I got my regular audiogram the audiologist definitely confirmed my left ear is worse and I've sensed this ever since I acquired tinnitus back in 1992. What that means as far as regeneration goes I don't know. I probably have nothing to lose by opting for this treatment even if there's a dead-zone it can't work with. Some improvement is better than none.

 

[Lucifer]

It would be nice if Frequency Therapeutics could figure out how much hair cells are regenerated with each FX-322 dosage but I will assume this would be hard to measure.

 

[FGG]

What's suspicious to me is the stereo aspect, where it's a mono signal in the YouTube clip and yet my perception of it fades off in my left ear as the frequency goes up but not my right. I also know that certain sounds like birds chirping or rain are much harder to hear just through my left ear. When I got my regular audiogram the audiologist definitely confirmed my left ear is worse and I've sensed this ever since I acquired tinnitus back in 1992. What that means as far as regeneration goes I don't know. I probably have nothing to lose by opting for this treatment even if there's a dead-zone it can't work with. Some improvement is better than none.

Just a guess, but if it's "harder to hear" in your left ear but not damn near impossible, you probably aren't profound in that range.

 

[AtlasFainted]

It would be nice if Frequency Therapeutics could figure out how much hair cells are regenerated with each FX-322 dosage but I will assume this would be hard to measure.

Pretty sure that's what they're trying to figure out during this trial. Not how many hair cells per se, but how much improvement comes with each additional dose (which in turn would indicate more hair cells).

 

[AtlasFainted]

Just a guess, but if it's "harder to hear" in your left ear but not damn near impossible, you probably aren't profound in that range.

Not to speak for him, but I think he's more worried about his tinnitus frequencies, not the lower ones where he can still perceive sound. Only guessing, because this is the case with me.

After this 'flat epithelia' stuff, I went from feeling certain that I'll have my ears back to normal within 2-3 years to not being sure if that will be the case until 15-20 years from now. The frequencies I hear slightly less volume in aren't the ones I'm worried about. I'm 95% sure those will be restored just fine sooner than later...

 

[dan]

It would be nice if Frequency Therapeutics could figure out how much hair cells are regenerated with each FX-322 dosage but I will assume this would be hard to measure.

We would still have glass ears, and if we think we can just go clubbing again, we won't have any more progenitor cells to burn if we kill them off again.

 

[GlennS]

Just a guess, but if it's "harder to hear" in your left ear but not damn near impossible, you probably aren't profound in that range.

Well, I'm fudging a bit. There have been times when I wake up while sleeping on one ear and turn around and suddenly hear the bird song or other faint noises like rustling leaves or road noise from a nearby freeway. Then I turn the other way to sort of "test" my bad ear and I simply can't hear it, at least can't hear it over the din of my tinnitus in that ear. It's a pretty bad combination.

The audiologist didn't even recommend a hearing aid for me. I was shocked, really. But the thing is, they're really only interested in speech parsing. They don't really care about upper frequency as long as you're still able to engage in conversation without saying "what" all the time, and frankly, I am saying what and mixing up what I think people are saying more than I used to.

If I were only 20 years younger I'd feel more optimistic about recent developments but I feel like maybe physiologically I'm close to running out the clock on being able to benefit much from some of this stuff. I hope I'm wrong.

 

[Jaysterk]

We would still have glass ears, and if we think we can just go clubbing again, we won't have any more progenitor cells to burn if we kill them off again.

I was under the impression that progenitor cells were stimulated to regrow hairs, not burned off?

And why would we still have glass ears?

 

[sssing]

Unless you're a rare case like me who tends to experience severely loud 15kHz ringing, despite the fact I can easily hear all the way up to about 18kHz without cranking the volume, and 19kHz has to be cranked to hear it. I don't think HF tinnitus is always related to HF hearing loss.

Yes, I somehow agree with @Flyingsheep that tinnitus frequency may not correspond to your hair cell loss location. But that your hearing dips on the audiogram corresponds to your cochlea region of damage because that was how they plotted the frequency map of the cochlea. They used people who had hearing losses after a certain frequency and studied their cochlear lesion location. So they used 27 donated human temporal bones with specific losses after 125Hz, 1000Hz, 2000Hz and so on and plotted what we know about the cochlear frequency map.

 

[HootOwl]

Unless you're a rare case like me who tends to experience severely loud 15kHz ringing, despite the fact I can easily hear all the way up to about 18kHz without cranking the volume, and 19kHz has to be cranked to hear it. I don't think HF tinnitus is always related to HF hearing loss.

It's important to remember though that the severity of tinnitus isn't necessarily related to the degree of hearing damage/loss you have, but instead to the degree of hyperactivity and central gain you have. Inflammation can also play a serious role. As a result, you can have very, very minor damage and yet still get very strong central gain.

The question as to why some people have such severe hyperactivity as a response to decreased cochlear input is still hotly debated, but one of the current theories being investigated is the ability of the Kv7 ion channels to self regulate. Those who don't develop hyperactivity even after significant hearing loss seem to have ion channels that re-equalize their voltage much easier or faster than those that do.

Edit: I should clarify that this relates to tinnitus of cochlear origin. Tinnitus stemming from TMJ, TMI, autoimmune, etc. could be different. The studies regarding central gain/hyperactivity all involve hearing loss, via noise or ototoxicty.

 

[Alex0o_o0]

... the current theories being investigated is the ability of the Kv7 ion channels to self regulate. Those who don't develop hyperactivity even after significant hearing loss seem to have ion channels that re-equalize their voltage much easier or faster than those that do.

Would this also hold through for non-noise induced tinnitus (e.g. tinnitus due to TBI)?

 

[HootOwl]

Would this also hold through for non-noise induced tinnitus (e.g. tinnitus due to TBI)?

For tinnitus that isn't of cochlear origin I'm not sure... I'm sorry, I would have to do more reading about that.

 

[Flyingsheep]

Those who don't develop hyperactivity even after significant hearing loss seem to have ion channels that re-equalize their voltage much easier or faster than those that do

Except that it's been a complete upside-down pyramid for me. I had very mild T for a good 6 months before it gradually got worse, and 2020 has been the year of greater worsening into the severe zone. Ironically the greatest worsening has started while I've been in the quietest environments possible. So if I have really minor damage but I have an extremely high central gain, why would it worsen substantially over time instead of improve slowly? Most people who have hearing damage start out with T at its worst, but mine started in the most mild form it could possibly be in.

 

[HootOwl]

Except that it's been a complete upside-down pyramid for me. I had very mild T for a good 6 months before it gradually got worse, and 2020 has been the year of greater worsening into the severe zone. Ironically the greatest worsening has started while I've been in the quietest environments possible. So if I have really minor damage but I have an extremely high central gain, why would it worsen substantially over time instead of improve slowly? Most people who have hearing damage start out with T at its worst, but mine started in the most mild form it could possibly be in.

My situation is similar to yours. Mine started out very mild as well, and then worsened considerably after very short acoustic exposures, no longer than a few seconds. There are actually many people who start out with mild tinnitus (quite a few on this forum) and then subsequent exposures causes it to worsen, or it worsens on its own.

As to why some exposure results in mild hyperactivity, and some in extreme, even within the same individual and at different points in that person's life? Why is it some people worsen and others get better - well, again it's not well understood. Fusiform activity in the DCN plays a role, inflammation plays a role, the ion channels - might - play a role, and even predicative brains (look up Will Sedley) probably have an active component.

The idea behind the Kv7 channel theory is it seeks to explain why some people have their tinnitus worsen or get better over time. The theory plays out like this: for some the channel voltage is able to recalibrate naturally, resulting in diminished tinnitus; in others it either can't recalibrate or does so in the "opposite direction" so to speak, resulting in even more hyperactivity and worsened tinnitus. It gets complicated, and even I don't fully understand all the papers to the degree that I would like. :/

The question you have is unfortunately one that even the brightest of researchers are still struggling with.

But ultimately, tbh it doesn't matter much to me why I have hyperactivity as long as I can fix the damage at its source.

 

[xyz]

Except that it's been a complete upside-down pyramid for me. I had very mild T for a good 6 months before it gradually got worse, and 2020 has been the year of greater worsening into the severe zone. Ironically the greatest worsening has started while I've been in the quietest environments possible. So if I have really minor damage but I have an extremely high central gain, why would it worsen substantially over time instead of improve slowly? Most people who have hearing damage start out with T at its worst, but mine started in the most mild form it could possibly be in.

Isn't this quite normal that tinnitus gets worse over time? The noise damage adds up and tinnitus worsens and if one is unlucky hyperacusis and other shit adds itself to the game. If I would still have the tinnitus as it was ten years ago I probably wouldn't be here. Only strange that you had worsenings while being in a quiet environment.

 

[AtlasFainted]

We would still have glass ears, and if we think we can just go clubbing again, we won't have any more progenitor cells to burn if we kill them off again.

I was under the impression that progenitor cells were stimulated to regrow hairs, not burned off?

And why would we still have glass ears?

Progenitor cells are divided and then turned into a new haircell. So you don't end up with less progenitor cells than you had before recieving FX-322.

There's no evidence at all to suggest we would have "glass ears". I'm going to take care of mine regardless, though.

 

[AtlasFainted]

Isn't this quite normal that tinnitus gets worse over time? The noise damage adds up and tinnitus worsens and if one is unlucky hyperacusis and other shit adds itself to the game. If I would still have the tinnitus as it was ten years ago I probably wouldn't be here. Only strange that you had worsenings while being in a quiet environment.

I don't know the scientific reasons, but lots of people have their tinnitus go away after a certain period. My brother had his go away completely but it took almost 2 years. His was from acoustic trauma & he still listened to loud music during that 2 year period.

It didn't come back even when he worked in a metal fabrication shop without ear protection. He still has hearing damage though.

I think our ears are complicated enough to say every case is extremely unique. Just clicking around this forum will prove that.

 

[Charburchar]

Isn't this quite normal that tinnitus gets worse over time? The noise damage adds up and tinnitus worsens and if one is unlucky hyperacusis and other shit adds itself to the game. If I would still have the tinnitus as it was ten years ago I probably wouldn't be here. Only strange that you had worsenings while being in a quiet environment.

I developed hyperacusis in a quiet environment, during lockdown.

 

[Lucifer]

Progenitor cells are divided and then turned into a new haircell. So you don't end up with less progenitor cells than you had before recieving FX-322.

There's no evidence at all to suggest we would have "glass ears". I'm going to take care of mine regardless, though.

I think once we get both FX-332 and synapses drug like Hough and OTO-413 then it should fix all issues in the ear.

Unless there is more involved in the ear then we may need other drugs other than regrowing hair cells and synapses.

 

[Flyingsheep]

Isn't this quite normal that tinnitus gets worse over time? The noise damage adds up and tinnitus worsens and if one is unlucky hyperacusis and other shit adds itself to the game. If I would still have the tinnitus as it was ten years ago I probably wouldn't be here. Only strange that you had worsenings while being in a quiet environment.

If I have minor damage that sparked this beast, there is no additional damage going on in the past 6 months. Taking a shower or having an ambulance drive by while staying inside and hearing the sound through walls isn't going to damage your hearing. That's just scientifically impossible. It has been worsening for some other reasons which we aren't even close to having answers for. I almost wish I had hearing damage so I knew something like this drug could help me. I don't know if there is anything else in the works that possibly can.