Frequency Therapeutics — Hearing Loss Regeneration

[GBB]

My outer hair cells are probably damaged because of noise. Consequently, I have constantly "swinging hair cells" and it produces tinnitus for me on the frequency in which the problem is. That's a rare cause of tinnitus but i have it.

Do you think that FX-322 could potentially help me? I don't have a problem with synapses. I think my problem is with hair cells.

Just out of curiosity, how would you know this regarding swinging hair cells?

 

[Diesel]

It's complicated but I trust the company to report very detailed results and not just a mean on this.

I was thinking about this last night... Since there are no specific exclusion or inclusion criteria for patients with bilateral, unilateral, or non-directional tinnitus in the Phase 2A, it's highly likely there are representation of all three in the study.

Frequency Therapeutics should know the status of each participant's tinnitus upon entry to the trial. Whether they have unilateral, bilateral, non-directional. Also, if unilateral, which side they have tinnitus.

I could see Frequency Therapeutics presenting data on a sample of patients that present unilateral tinnitus in the treated ear, and displaying the change in TFI over time; as well as other audiogram improvements (ext. high frequency), for example.

Based on what we know about the prevalence of unilateral tinnitus, it may only be 8-10 patients, but its likely they would be randomly distributed across placebo, 1x, 2x, 4x dose cohorts.

It must be true, because this is exactly the type of selective data presentation that will get all the skeptics fired up for weeks on this forum.

 

[Trevor_phillips]

Just out of curiosity, how would you know this regarding swinging hair cells?

"Spontaneous oscillations of ECCs, producing active mechanisms without prior sound stimulation, could be followed by physiological effects: activation of CCIs and auditory fibers. The message going to the nervous system would be as "real" as nature, and the subject would hear a frequency-tuned hissing sound at the level of the CCE lesion.

Some authors implicate the median efferent system in triggering spontaneous oscillations and therefore tinnitus. However, it is only in very rare cases that these oscillations could be objectified in the form of spontaneous oto-emissions corresponding to the frequency of subjective tinnitus ..."

The website link:
http://www.cochlea.eu/pathologie/acouphenes-mecanismes

So, I think I have that.

 

[FGG]

"Spontaneous oscillations of ECCs, producing active mechanisms without prior sound stimulation, could be followed by physiological effects: activation of CCIs and auditory fibers. The message going to the nervous system would be as "real" as nature, and the subject would hear a frequency-tuned hissing sound at the level of the CCE lesion.

Some authors implicate the median efferent system in triggering spontaneous oscillations and therefore tinnitus. However, it is only in very rare cases that these oscillations could be objectified in the form of spontaneous oto-emissions corresponding to the frequency of subjective tinnitus ..."

The website link:
http://www.cochlea.eu/pathologie/acouphenes-mecanismes

So, I think I have that.

That site hasn't been updated since 2016. New information suggests that tinnitus is not "generated inside the cochlea" but is actually a phantom sound (like "phantom limb") resulting from auditory input being interfered with.

In fact, you can remove your entire cochlea and still have tinnitus.

 

[Trevor_phillips]

That site hasn't been updated since 2016. New information suggests that tinnitus is not "generated inside the cochlea" but is actually a phantom sound (like "phantom limb") resulting from auditory input being interfered with.

In fact, you can remove your entire cochlea and still have tinnitus.

Okay thanks. But if we admit that this information is true, would FX-322 benefit me?

 

[FGG]

Okay thanks. But if we admit that this information is true, would FX-322 benefit me?

I think we can assume you don't have "swinging hair cells" as that site is the only place I have ever seen that and they didn't cite any sources.

Have you had an extended audiogram?

 

[Jack V]

Okay thanks. But if we admit that this information is true, would FX-322 benefit me?

Like any drug for any condition... you really won't know until you try it.

 

[Diesel]

Okay thanks. But if we admit that this information is true, would FX-322 benefit me?

 

[acute]

Would FX-322 benefit people without hearing loss? I mean, people with seemingly perfect audiogram but who still have tinnitus.

 

[FGG]

Would FX-322 benefit people without hearing loss? I mean, people with seemingly perfect audiogram but who still have tinnitus.

Do you have a normal extended audiogram or just standard?

Lots of people are told they don't have hearing loss but when they get an extended audiogram (vs a standard audiogram), they find out they do.

Another group of people have cochlear synaptopathy where they have a form of "hidden hearing loss" that doesn't show up on audiogram and may not even be noticeable to them. OTO-413 is the drug for that condition in trials.

What is your cause?

 

[Philip83]

Would FX-322 benefit people without hearing loss? I mean, people with seemingly perfect audiogram but who still have tinnitus.

This discussion has been had many time over in this thread, just read the last 5-10 pages and you'll know more. In short, no one knows, but there's a chance.

 

[serendipity1996]

Would FX-322 benefit people without hearing loss? I mean, people with seemingly perfect audiogram but who still have tinnitus.

If you truly have no hearing loss at all, even at extended high-frequencies then no, it wouldn't. It's primarily a hearing loss drug aimed at regenerating sensory hair cells. That said, current diagnostics are pretty primitive so a lot of people are told they have 'perfect' hearing when they really don't - if you got tinnitus from noise, chances are you have some hair cell loss.

 

[Flyingsheep]

What I always wonder is if you just absolutely can't pinpoint why your tinnitus started, why it continues to worsen every year, and you still get perfect hearing test results, is it even possible to convince an ENT to agree to try FX-322 anyway? I feel like that is another substantial barrier.

 

[Orions Pain]

Would FX-322 benefit people without hearing loss? I mean, people with seemingly perfect audiogram but who still have tinnitus.

Have you seen an actual copy of your audiogram? My ENT told me my hearing was "perfect" but when I saw my audiogram myself, I'm close to minor hearing loss on one frequency. I would recommend obtaining a copy of your audiogram.

I hope this is allowed since this is an FX-322 thread, but over on the University of Minnesota bimodal stimulation device thread someone brought up that one theory is that it's not so much severe hearing loss that causes tinnitus, but more "dips" in hearing. So someone who has lots of hearing loss across a bunch of frequencies that happened slowly over many years is less likely to have tinnitus than someone who has hearing that falls in the normal range (between 0 and 20 dB) but has a random dip on an audiograms even if it doesn't fall into the hearing "loss" area.

Most people here probably do have hearing loss, especially at higher frequencies that aren't assessed on a standard audiogram.

 

[katri]

What I always wonder is if you just absolutely can't pinpoint why your tinnitus started, why it continues to worsen every year, and you still get perfect hearing test results, is it even possible to convince an ENT to agree to try FX-322 anyway? I feel like that is another substantial barrier.

We'll worry about that later. I'm sure things would work out a little better in terms of talking about hidden hearing loss and the results it's had on other people's tinnitus.

 

[Orions Pain]

What I always wonder is if you just absolutely can't pinpoint why your tinnitus started, why it continues to worsen every year, and you still get perfect hearing test results, is it even possible to convince an ENT to agree to try FX-322 anyway? I feel like that is another substantial barrier.

I would assess your history with noise exposure and the months leading up to tinnitus starting, very often it's a delayed reaction. There is no such thing as perfect hearing results especially if you haven't gotten an extended audiogram. If FX-322 works, it could change the way audiologists treat hearing. They don't test past 8 kHz because they consider it irrelevant since there's nothing they can do.

They do extended audiograms on patients undergoing chemo to monitor hearing loss, so clearly they are aware to some extent that hearing at those frequencies matters. They just don't do it for regular people because it's not profitable for them in any way.

I'm sure if FX-322 works, things will change.

 

[Diesel]

What I always wonder is if you just absolutely can't pinpoint why your tinnitus started, why it continues to worsen every year, and you still get perfect hearing test results, is it even possible to convince an ENT to agree to try FX-322 anyway? I feel like that is another substantial barrier.

You won't have to convince an ENT by the time FX-322 is on the market. They will be inclined to try it and see how it goes. If the ENT still says no, I'm sure at that point sites like this and Frequency Therapeutics will have lists of ENTs that will gladly give you the goop.

 

[Flyingsheep]

I would assess your history with noise exposure and the months leading up to tinnitus starting, very often it's a delayed reaction. There is no such thing as perfect hearing results especially if you haven't gotten an extended audiogram. If FX-322 works, it could change the way audiologists treat hearing. They don't test past 8 kHz because they consider it irrelevant since there's nothing they can do.

They do extended audiograms on patients undergoing chemo to monitor hearing loss, so clearly they are aware to some extent that hearing at those frequencies matters. They just don't do it for regular people because it's not profitable for them in any way.

I'm sure if FX-322 works, things will change.

I've had zero luck convincing any ENT or audiologist to do an extended audiogram. I've done my own testing to the best of my own ability with proper speakers and I can hear the full range without any noticeable dips, especially in the high range. I don't write off hearing loss completely, I mean it's most likely that I have hidden hearing loss that is just totally unnoticeable and I'm sure the majority of the population does. My piercing tinnitus is probably a result of maladaptive neuroplasticity to the gradually minor changes in my hearing.

So my best option would be to try FX-322 since OTO-413 is going to take longer. There's nothing to lose I guess.

 

[Orions Pain]

I've had zero luck convincing any ENT or audiologist to do an extended audiogram. I've done my own testing to the best of my own ability with proper speakers and I can hear the full range without any noticeable dips, especially in the high range. I don't write off hearing loss completely, I mean it's most likely that I have hidden hearing loss that is just totally unnoticeable and I'm sure the majority of the population does. My piercing tinnitus is probably a result of maladaptive neuroplasticity to the gradually minor changes in my hearing.

So my best option would be to try FX-322 since OTO-413 is going to take longer. There's nothing to lose I guess.

My hope is that if they have really favorable tinnitus outcomes with their current trials, they'd eventually explore addressing tinnitus with "normal" audiograms as well. Curing hearing loss is major but finding a treatment for tinnitus that works is just as major.

I honestly wouldn't worry about all that until we get some sort of actual data on tinnitus itself.

FGG has pointed out that Universities may be more willing to do an extended audiogram than private audiology offices.

 

[FGG]

I've had zero luck convincing any ENT or audiologist to do an extended audiogram. I've done my own testing to the best of my own ability with proper speakers and I can hear the full range without any noticeable dips, especially in the high range. I don't write off hearing loss completely, I mean it's most likely that I have hidden hearing loss that is just totally unnoticeable and I'm sure the majority of the population does. My piercing tinnitus is probably a result of maladaptive neuroplasticity to the gradually minor changes in my hearing.

So my best option would be to try FX-322 since OTO-413 is going to take longer. There's nothing to lose I guess.

I checked your location on your profile. You can get it done at Kent State. Someone else here got his extended audiogram done there.

 

[Joe72]

Pretty similar experience - for me it was a 2 second train horn blast that sent me from what was a mild case that went away over a few years to severe. It was audible above everything with crazy distortion of masking noise, and HYPER reactivity. I really thought I was gonna die to be honest. If it kept that way, I would be living outside in a tent, on disability, no doubt. I've since had it reduce a bit from 24/7 severe, to usually, severe only after 2pm. The beginning of the day it is quieter now than when I got it 5 months ago, and consistently starts the day the same way, at a mild level, and then gets louder over the day. Distortion is also down but not gone.

Wow, yes, what you describe is very similar to what is happening to me right now. It's quieter in the morning before all the neurons begin firing, then about 1 hour after waking up it's full volume right up until bedtime.

What's interesting is that we both had a mild case of it early on, and lived with it, then boom... a loud event and it becomes much worse. I am starting to think that my brain was already defective in it's wiring due to lifelong stress, job, etc, and that all it took was one loud event to take my auditory system into cytokine mode and re-wire itself in an incorrect way to make up for the hearing loss.

Having this group to post to, and talk about it is such a help. No one in my family is understanding of the condition at all. Truth be told, it's my young children that keep me from going A-Wall. I need to be there for them. I take a deep breathe everyday, and am thankful that my children are healthy, and that we can enjoy spending time together. Otherwise I'm pretty much alone.

 

[Cernuto]

Another thing that occurred to me about audiograms (extended or not) is they usually are for a limited number of frequencies. You could possibly be missing entire groups of hair cells between the tested frequencies?

If the audiogram tested for 2 kHz and 4 kHz, and you are missing everything in between (say 2.5 kHz-3.5 kHz), the audiogram would never show it?

 

[Philip83]

Another thing that occurred to me about audiograms (extended or not) is they usually are for a limited number of frequencies. You could possibly be missing entire groups of hair cells between the tested frequencies?

If the audiogram tested for 2 kHz and 4 kHz, and you are missing everything in between (say 2.5 kHz-3.5 kHz), the audiogram would never show it?

Yes. @Diesel posted about this a couple of pages back:

https://canadianaudiologist.ca/issue/volume-7-issue-6-2020/feature-1/

 

[Pero1234]

Yes. @Diesel posted about this a couple of pages back:

https://canadianaudiologist.ca/issue/volume-7-issue-6-2020/feature-1/

View attachment 42457

I suspect this is the case with me.

My standard audiogram shows impeccable hearing. Measured up to 8 kHz.

When I test via YouTube with a constant tone, I definitely hear a dip around 4 kHz. Almost like - over the span of 500 Hz - someone is slowly turning down the volume a notch or two before gently turning it back up. Very strange.

Then my hearing fizzles out completely around 12.5-13 kHz.

I am aware YouTube and speakers / headset are not accurate testing equipment, but it corresponds to many theories out there concerning tinnitus and hearing loss.

Of course the question remains: where is my tinnitus coming from? My hearing loss above 12 kHz? Or that dip at 4 kHz...?

I think I may have more luck in getting it "fixed" with FX-322 if the culprit is located above 12.5 kHz.

We will have to wait and see. What an exciting / pivotal year 2021 will be!

 

[FGG]

Yes. @Diesel posted about this a couple of pages back:

https://canadianaudiologist.ca/issue/volume-7-issue-6-2020/feature-1/

View attachment 42457

I'm honestly surprised no one tried to make a more customizable hearing aid knowing this occurs. I think they would be more universally at least helpful with tinnitus (though not curative) if they did.

But perhaps part of the problem is the audiology appointment would be hours long. Still, there is a niche and they could charge appropriately.

 

[d'Wooluf]

I'm honestly surprised no one tried to make a more customizable hearing aid knowing this occurs. I think they would be more universally at least helpful with tinnitus (though not curative) if they did.

My second set of hearing aids used a self-programming paradigm. The user was required to match volumes of tones at four frequencies. Yes, a whole four frequencies. I often wondered why not forty? It was my time I was using. Not theirs. It's as though it was more important to set your aids up easily and speedily than optimally.

I'm still hoping that we'll eventually see hearing aids with sophisticated user-adjustment capabilities.

But perhaps part of the problem is the audiology appointment would be hours long. Still, there is a niche and they could charge appropriately.

Yep. Or they could develop automated testing booths. I don't think it would be hard to do.

 

[Diesel]

My second set of hearing aids used a self-programming paradigm. The user was required to match volumes of tones at four frequencies. Yes, a whole four frequencies. I often wondered why not forty? It was my time I was using. Not theirs. It's as though it was more important to set your aids up easily and speedily than optimally.

I'm still hoping that we'll eventually see hearing aids with sophisticated user-adjustment capabilities.

Yep. Or they could develop automated testing booths. I don't think it would be hard to do.

I don't see why Audiologists couldn't do a menu of packages, and charge more per package depending on the complaint and feedback from the patient. This is standard for other types of diagnostics in other industries, where they start with a 30-min broad diagnostic, and determine if a deeper inspection is needed.

For example:

Standard Audiogram - 125 Hz - 8 kHz - 7 Band Diagnostic - Fee: $200
Standard + Extended HF - 125 Hz - 16 kHz - 12 Band Diagnostic - Fee: $400
High Fidelity Audiogram - 125 Hz - 16 kHz - 30 Band Diagnostic - Fee: $800
Custom Assessment - 125 Hz - 16 kHz - Custom Range Detailed (IE: 200 Hz steps between 6 kHz and 8 kHz) - Fee: $1000

This wouldn't be super hard to add to their list of services, and since Audiologists are basically sales people, they can tier-out patients.

So the sales process could be:

- We do the standard test, but it isn't very detailed and don't give you a "personal assessment" of your hearing. But for $X more, we can give you a specific assessment of your hearing.

- For patients with X, Y, Z, issues... because they're more complex, we recommend going right to the High Fidelity or Custom Assessment, so we can see exactly where you'll need treatment.

Maybe Audiologists aren't creative enough to sell it this way. I have met a few doctors in my career, and I can say they mostly lack business creativity.

 

[Drachen]

We do the standard test, but it isn't very detailed and don't give you a "personal assessment" of your hearing. But for $X more, we can give you a specific assessment of your hearing.

So, from what I'm hearing, is the first sentence of this supposed to be what I expect next week when I visit the audiologist?

I'm really concerned that I won't be able to fully identify where my problems may lie. I honestly thought you could just ask them to do more frequencies, and that's all there is to it.

 

[FGG]

So, from what I'm hearing, is the first sentence of this supposed to be what I expect next week when I visit the audiologist?

I'm really concerned that I won't be able to fully identify where my problems may lie. I honestly thought you could just ask them to do more frequencies, and that's all there is to it.

In the US, a standard audiogram is: 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, 8000 Hz and that's it.

Occasionally, they include 125 Hz.

Extended audiograms include: 10 kHz, 12 kHz, 14 kHz, 16 kHz.

 

[Drachen]

In the US, a standard audiogram is: 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, 8000 Hz and that's it.

Occasionally, they include 125 Hz.

Extended audiograms include: 10 kHz, 12 kHz, 14 kHz, 16 kHz.

Yeah, which doesn't seem to convey much if you had anything by the way of hidden hearing loss. I guess that's why it's "hidden", lol.

Is there much value in an audiogram otherwise then? Considering you won't know what happens in between the intervals and the fact it only goes up to so high, I'm not sure what information I can glean from it.

Since you usually lose hearing at the highest frequencies first, do changes or dips on the lower frequencies mean you have above mild hearing loss?

I'm so confused how this all plays together.