Frequency Therapeutics — Hearing Loss Regeneration

Discussion in 'Research News' started by RB2014, Dec 8, 2016.

    1. Diesel

      Diesel Member Benefactor

      Location:
      Ohio
      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      I experience this myself on occasion.

      I think FX-322 will help with this condition. It seems like the underlying issue is likely damaged hair cells sending improper signals to the brain, or the brain trying to compensate for sounds erroneously due to missing hair cells.

      If FX-322 works as intended, I think it’s possible the following will help reduce the symptom: The damaged/missing cells are replaced with functioning ones, and the brain gets correct signals. The malfunctioning cells stay, but a population of new cells are created in the same area; the increased “bandwidth” of signal from properly function cells dramatically reduces the effect of the dysfunctioning cells.
       
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    2. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      Is there any data to suggest your tinnitus frequency is aligned to the actual frequency of hearing loss? Just trying to intuit some simple stuff here; for example my tinnitus is about 14 kHz, so wondering if because FX-322 hits high frequencies first, I would theoretically be a good candidate.
       
    3. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Can you get an extended audiogram? If you had OHC loss at 14 kHz specifically you could see it on an extended audiogram. Synapse loss alone wouldn't show up though.
       
    4. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      I am planning on it at some point - right now my ears are fragile/reactive so don't even wanna drive to the doctor. I agree that would clear up any ambiguity. I know my audiogram is "normal" to 8 kHz so hoping loss is above that or synaptic, otherwise I'm gonna be an orphan case of noise-induced tinnitus without an actionable solution :(
       
    5. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      I wish we could annihilate the misfunctioning cells. I have this too and my fear is even with new cells, I'll just be diluting the effect rather than curing it. I am going to try Keppra soon to see if it can help reduce the distortion, as some hypothesize it is a subset of hyperacusis.
       
    6. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      I think the theory that tinnitus is somehow related to specific frequencies is inevitably incredibly misguided. Something tells me that the tinnitus is not linked to some specific frequency because there are people with hair cell loss and no tinnitus and people with no hair cell loss and tinnitus. I think that we will find that tinnitus is more connected to the synapses than the hair cells and this tends to be supported by some of the research that has been done by groups like Hough Ear Institute. I think the reason FX-322 has happened to help tinnitus is because synapses have been regrown when FX-322 grows both new hair cells and synapses together.

      While having greater hearing volume and also actual clarity is going to assist, I believe that there is a lot of information suggesting that the synapses are what will improve the tinnitus since seemingly they are what connects it all together.
       
    7. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      I hope this is the case as it seems like an easy fix, but I have bad tinnitus and perform really well on speech in noise tests meant to tests the synapses, so I don't know what to believe.

      I get scared out of my mind sometimes pondering, what if for me this is all a brain problem - the ears are working fine but the brain is maladaptive and making changes. My worst fear is truly getting slowly worse over time with no clear catalyst...
       
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    8. Diesel

      Diesel Member Benefactor

      Location:
      Ohio
      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      An anecdotal data point for you.

      I can hear up to roughly 12 kHz in my left ear at a reasonable decibel level. The tinnitus in the left ear sounds like high-frequency static and a 13-14 kHz tone. I don't have "hear all the time" tinnitus in my right ear; and when I hear a 13-14 kHz tone in my right ear at about 20 dB, it sounds like I'm hearing it in "stereo" because it balances with the phantom sound being produced in my left ear; if that makes sense.

      I have concluded that the tinnitus I experience in my left ear is directly related to lost hair cells at those high frequencies (12 kHz +) due to noise exposure; resulting in the tone + static tinnitus.

      I would conclude that FX-322 working its way down into the cochlea may help a lot of people with all or part of their tinnitus that is experienced in the high frequency range. New IHC/OHC giving the brain a signal should quiet down the "phantom" sound sensation.
       
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    9. Diesel

      Diesel Member Benefactor

      Location:
      Ohio
      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      I don't dispute the overall point you're trying to make here... but we do know that hair cell loss is associated with hearing loss. So, less available functioning hair cells = less hearing (less sensitivity to sound).

      Do you think its plausible that people experiencing tinnitus have a combination of damaged/dead hair cells, "normal" hair cells connected to the synapse, and "normal" hair cells with broken synapses?

      If so, would it also be plausible that FX-322 treating the damaged/dead hair cells populations might create enough new "signal" for the brain to dramatically reduce tinnitus as a symptom?

      I tend to think more and more as I learn more about hearing loss that its clear the biology of the cochlea doesn't correlate directly with the metrics used to determine hearing function on the audiogram.

      For example, if my math is correct, there are roughly 3500 inner hair cells and 12,000 outer hair cells in the cochlea. Yet, a human can hear from 20 Hz to 20,000 Hz. We also know that "normal" human hearing is sensitive enough to detect roughly a 1hz difference between a set of pure tones. So, the difference between 3500 Hz and 3501 Hz. However, the count of cells doesn't necessarily correlate 1:1 with the sensitivity to sound. This makes sense since the biology doesn't correlate with the metric (Hz). What it tells me though, is that brain uses one or more cells to differentiate and sense sound. I also recall a research article shared a while back that claimed that the brain can "repurpose" hair cells to hear sounds after damage has occurred. So, perhaps the cell that generally hears 4000 Hz-5000 Hz can maybe be stretched to hear 3800 Hz-5200 Hz if its neighbors are damaged?

      So, when I consider a damaged cochlea with "mixed" pathology as described above; I cant help but think that maybe repairing even a partial count of the population with new "signaling" providers that is enough to begin improving hearing and thereby reducing tinnitus.

      NOTE: I do agree for true full "restorative" treatment, we're going to need cell regrowth and synapse repair.
       
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    10. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I passed the speech in noise test just fine but can't watch movies anymore without captions. I have extensive high frequency and ultra low frequency damage but I don't believe synaptopathy is a big component of mine, though I could have that along with confirmed widespread ultra high frequency OHC damage.
       
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    11. weab00
      Alone

      weab00 Member Benefactor

      Location:
      depression-ville
      Tinnitus Since:
      04/2019
      Cause of Tinnitus:
      noise, whiplash; 08/20 H
      And there’s no way to target the damaged but not dead hair cells?

      I’m wondering if regrowing hair cells will be enough to significantly abate hyperacusis until synapse treatments come out. Maybe not enough to go to a club or concert, but enough to walk down the street without stabbing pain and lower your brain’s over all gain.
       
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    12. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      The repurposing is behind a lot of tinnitus fading I think - brain gets new signal but needs time to adapt. I assume after FX-322 it would take like a year for your tinnitus to fade. Consider the people who get earwax removed, and have perfectly healthy ears, and it still takes a year for them to return to normal...
       
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    13. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      I don’t disagree with this at all. Actually I am of the view that a combined issues of hair cells, inflammation and synapses cause tinnitus. I also am of the view the brain can rework to hear specific sounds both before and after damage. I don’t think that this will be an issue at all.

      I think that the restoration of hair cells probably will be a part of reducing tinnitus because if you look at some non-injury tinnitus such as through jaw movement, it is I think caused by reduced auditory input.

      I therefore think that people are going to have to have both FX-322 and PIPE-505 or similar since we obviously know many have a mixture between busted synapses and synapses and hair cells together. I still think that the inflammation will have some significant support with reducing tinnitus too though. There tends to be a very real likelihood that if you have gotten a hurt ear that it is incredibly likely to be inflamed like if you strained your thigh etc.

      Essentially I think that when doctors start to trial treat people because they don’t know what is exactly going on they will then be able to try and work out what is happening and also actually what sort of treatment they need to use in order to deal with or have a better idea of how to deal with specific stuff.
       
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    14. Diesel

      Diesel Member Benefactor

      Location:
      Ohio
      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      Frequency Therapeutics has claimed that the drug targets hair cells that are dead or damaged.

      Unfortunately, hyperacusis is such a catch-all diagnosis that we don’t know how FX-322 will help. That’s probably why it’s not being evaluated in the Phase 2a.

      I personally think that symptoms including “loudness” , recruitment, distortions, reactivity, and possible some level of pain relating to sound will be treated by replacing dead or damaged hair cells.
       
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    15. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      I think this tends to be fairly accurate about hyperacusis. However, I definitely think that if there are anecdotal comments about people with hyperacusis being helped like there were with tinnitus then there may be some secondary measure testing done in the subsequent clinical trial. Though I think this might be harder than doing it for tinnitus because tinnitus is much, much more easily identifiable both by the doctor and patient.
       
    16. weab00
      Alone

      weab00 Member Benefactor

      Location:
      depression-ville
      Tinnitus Since:
      04/2019
      Cause of Tinnitus:
      noise, whiplash; 08/20 H
      I really hope this gets rid of enough pain to endure things like social gatherings without stabbing in my ear. I can live without all the really loud shit till synapse treatments.
       
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    17. frpp

      frpp Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      Tmj, Nihl, ototoxic drugs, nerve/ vascular issues
      Ditto. Hoping FX-322 can cure TTTS too. The constant reactive ear spasms are killing me man.
       
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    18. Diesel

      Diesel Member Benefactor

      Location:
      Ohio
      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      The best they can do with hyperacusis is quality-of-life / hearing handicap surveys. There currently isn’t a validated survey for hyperacusis like there is for tinnitus (TFI). So it has to be inferred that the hearing handicap score may reflect some with hyperacusis improving.
       
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    19. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      Does anyone understand the mechanism by which damaged hair cells would be identified for replacement?
       
    20. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Since it works by activating a support cell to asymmetrically divide, and doesn't cause this division when there is an intact hair cell, I can only assume there is a feedback loop that a normal hair cell would have with its associated support cell that the support cell doesn't receive when the hair cell is not sending this normal signal.
       
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    21. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      This makes a lot of sense although if tinnitus and/or hyperacusis could be treated through one of or multiple of these medicines then I can almost see that such a measure would be redundant.

      Really I could see such a measure being developed for hyperacusis had people reported benefit from these medicines, however that would probably only be if there was partial relief.
      When you say mechanism, do you mean the way they are replaced? I thought that it is just a matter of finding where those damaged hair cells are and actually sending a signal to regrow them should that need to be done.
       
    22. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      Okay so it's very plausible a bent hair cell misfiring and creating some sort of distortion could still have an intact handshake with its respective support cell, and so this treatment might leave bent hair cells as is.
       
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    23. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I assume you mean the stereocilium is bent, not the hair cell itself because a bent "hair cell" would be pretty well destroyed.

      Stereocilium naturally are supposed to have movement during normal hearing. For a hair cell to remain "bent", either the actin cross linking at the tips is damaged (and this actually is self repairing in a reference I found ages ago) or it's broken at the insertion site which means the cell itself is damaged too.

      The other option (and this is my theoretical opinion) is if the stereocilium are temporarily being pushed down by something like inflammation.

      Either way, on the podcast there was a question about damaged but not destroyed hair cells and the reply was that in all the cochlea that they looked at they didn't see this as a significant problem at all. I realize individual theoretical lesions weren't asked about but i really don't think this is a likely worry at all.

      Humans have very different apoptosis pathways and i wonder if damaged hair cells are just more likely to be destroyed based on lack of weird pathology like that being reported in humans that I can find on autopsy studies.
       
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    24. sensualmosquito
      Dreaming

      sensualmosquito Member

      Location:
      New Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      6-8 khz HL, T and H from gunshots
      I probably bent the living hell out of mine. I hope that with newer, better functioning cells present that the effect of these more dysfunctional cells can be diminished. I remember hearing though somewhere that we have already discovered a significant portion of the genes that control development of the ear. Perhaps, as we learn more, there will be some sort of solution to that as well. Although I'm afraid I'll be an old man by then!
       
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    25. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      I think we can agree that, just like tinnitus, hyperacusis is caused by auditory injury. As a result, I think that if you repair the cochlea(s) then there tends to be a good prospect probably of resolving the issues that cause hyperacusis.
      I think that this is similar to my case where my issues seem to be more hair cell than synapse related. Consequently I can believe that I will be much more likely to benefit by having a hair cell medicine rather than a synapse medicine, though I will probably trial treat to see what actually occurs with the testing post treatment. I definitely think though that I will use the inflammation medicine as well.
      Where do you get such information regarding bent hair cells?

      What would a hair cell do if it is bent and not damaged? Why would this be any different in its operation/function to a normal hair cell?
       
    26. sssing

      sssing Member Benefactor

      Tinnitus Since:
      2019
      Cause of Tinnitus:
      cold
      I experience this as well, a morse code sound above car engines and car brakes. I didn’t even know how to put it in words. Thanks for giving it a name...
       
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    27. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      Thank you, I appreciate the clarification. I did have a small conversation in another thread with @Juan and @serendipity1996 about the cause of distortion, and it was posited that this was due to “bent hair cells”, as opposed to a nerve issue. In my tinnitus life, I am guilty of not using primary sources - I often rely on others to developed a more informed opinion. It’s good that it sounds like any sort of “bent” damage would be addressable.
       
    28. GBB

      GBB Member

      Location:
      NYC
      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Microsuction / Additional Acoustic Trauma in Close Proximity
      See this thread - the bent hair cell conversation was speculative.

      Has Anyone Experienced a Transition from Fragile Hyperacusis Ears Back to Durable Normal Ears?
       
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    29. Street Novelist
      Depressed

      Street Novelist Member

      Location:
      Bay Area
      Tinnitus Since:
      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      All of this negativity... we don' t know how it will work. I wish the speculating would stop. Have faith. It will work.
       
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    30. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Absolutely agree with this. I think that the treatment will totally work too.
       
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