• We have updated Tinnitus Talk.

    If you come across any issues, please use our contact form to get in touch.

Frequency Therapeutics — Hearing Loss Regeneration

#10,291
@serendipity1996 I agree with both your points, I get tunnel vision based on my and similar cases but you're right pain hyperacusis isn't necessarily acoustic shock related and who knows how genetics and our individual chemistries come into play.

Can I ask because I'm not aware of your background, have you had acoustic shock that lead to noxacusis as well? You mention that you had gradual noxacusis. If you did, how did the pain compare in both cases? I'm asking because one of my ears is full on acoustic shock invoked pain hyperacusis, but my other ear has also experienced very very mild pain hyperacusis symptoms in the past but never acoustic shock, in this ear it doesn't last long and generally goes away again to the point where it might as well be recovered. There basically is no comparison when comparing the two different instances of pain though, one is crippling, while the other is nothing more than a very mild, but familiar sensation.

I guess where I'm coming from because I really don't know the answer to this, but is the crippling, debilitating noxacusis that people are desperate to cure generally considered more to be triggered by acoustic shock, or can the gradual non acoustic shock noxacusis also become just as debilitating?

Just an aside, I wonder if there's ever been a study to compare the activation status of type 2's between noxacusis sufferers vs non sufferers. I don't know if this could even be done in living subjects, if not possibly post mortem as long as the noxacusis history was known.
 
#10,293
serendipity1996 said:
What about people who experience pain hyperacusis without also experiencing an acoustic shock? My first experience with noxacusis was more gradual as opposed to being kickstarted by a sudden event. According to the team at Johns Hopkins (Fuchs et al) even progressive damage over time can increase ATP levels in the cochlea.
Click to expand...
I'm starting to question the use of "acoustic shock/trauma" as being anything other than really "fast" NIHL. It seems to be thrown around like its a special cause of hearing loss; and somehow those who experienced it will need some special treatment. Where really, it's just same old cell death/damage happening really quickly.

Acoustic shock sometimes does and does not cause hyperacusis; other than it being a faster way to lose hearing, what makes it any more unique than gradual NIHL?
NewLionel said:
The fact that FX-322 might not work on hyperacusis makes me (very) depressed.

My hyperacusis went through the roof after an alarm went off/acoustic shock.
Click to expand...
The great news is, there has never been a for-fact "NO it won't help..." but here's a helpful theory:

There seems to be a fair amount of agreement that OHC damage/death are related with several symptoms associated with hyperacusis. Enough OHC damage/death associated with their respective Type-II nerve may be triggering many of these symptoms.

FX-322 causes progenitors to regenerate OHC that are damaged, dead or missing. Called Progenitor Cell Activation (PCA).

When PCA occurs. The brand-new OHC are also reconnected to the appropriate nerve; the Type-II nerve in this case. The same way it was done in the womb; as nature intended.

It stands to reason with a fresh batch of new, living OHC connected to the Type-II nerve, symptoms related to hyperacusis would begin to fade or at least be reduced over time.

I, for one, will be looking closely at the results of the Hearing Handicap and Quality-of-Life survey data from the Phase 2A. Certainly some of the 96 participants have hyperacusis; they all will have significant hearing loss for starters, so prevalence of tinnitus and hyperacusis should be higher than "normal." Considering how greatly hyperacusis affects QOL, I would expect those scores to significantly improve post FX-322.
 
#10,296
Diesel said:
I'm starting to question the use of "acoustic shock/trauma" as being anything other than really "fast" NIHL. It seems to be thrown around like its a special cause of hearing loss; and somehow those who experienced it will need some special treatment. Where really, it's just same old cell death/damage happening really quickly.

Acoustic shock sometimes does and does not cause hyperacusis; other than it being a faster way to lose hearing, what makes it any more unique than gradual NIHL?

The great news is, there has never been a for-fact "NO it won't help..." but here's a helpful theory:

There seems to be a fair amount of agreement that OHC damage/death are related with several symptoms associated with hyperacusis. Enough OHC damage/death associated with their respective Type-II nerve may be triggering many of these symptoms.

FX-322 causes progenitors to regenerate OHC that are damaged, dead or missing. Called Progenitor Cell Activation (PCA).

When PCA occurs. The brand-new OHC are also reconnected to the appropriate nerve; the Type-II nerve in this case. The same way it was done in the womb; as nature intended.

It stands to reason with a fresh batch of new, living OHC connected to the Type-II nerve, symptoms related to hyperacusis would begin to fade or at least be reduced over time.

I, for one, will be looking closely at the results of the Hearing Handicap and Quality-of-Life survey data from the Phase 2A. Certainly some of the 96 participants have hyperacusis; they all will have significant hearing loss for starters, so prevalence of tinnitus and hyperacusis should be higher than "normal." Considering how greatly hyperacusis affects QOL, I would expect those scores to significantly improve post FX-322.
Click to expand...
I am reposting this link and excerpt supporting the notion that regenerating OHCs will help with hyperacusis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383716/
 

Attachments

  • OHC and hyperacusis.jpg
    OHC and hyperacusis.jpg
    464.4 KB · Views: 67
#10,299
100Hz said:
@serendipity1996 I agree with both your points, I get tunnel vision based on my and similar cases but you're right pain hyperacusis isn't necessarily acoustic shock related and who knows how genetics and our individual chemistries come into play.

Can I ask because I'm not aware of your background, have you had acoustic shock that lead to noxacusis as well? You mention that you had gradual noxacusis. If you did, how did the pain compare in both cases? I'm asking because one of my ears is full on acoustic shock invoked pain hyperacusis, but my other ear has also experienced very very mild pain hyperacusis symptoms in the past but never acoustic shock, in this ear it doesn't last long and generally goes away again to the point where it might as well be recovered. There basically is no comparison when comparing the two different instances of pain though, one is crippling, while the other is nothing more than a very mild, but familiar sensation.

I guess where I'm coming from because I really don't know the answer to this, but is the crippling, debilitating noxacusis that people are desperate to cure generally considered more to be triggered by acoustic shock, or can the gradual non acoustic shock noxacusis also become just as debilitating?

Just an aside, I wonder if there's ever been a study to compare the activation status of type 2's between noxacusis sufferers vs non sufferers. I don't know if this could even be done in living subjects, if not possibly post mortem as long as the noxacusis history was known.
Click to expand...
That's a good question. To be honest, this whole area of 'acoustic shock' vs 'hyperacusis' vs 'acoustic trauma' is very blurred. I'm not very clued-up on acoustic shock but it seems that it's characterised by the reaction to an unexpected, loud sound. I wouldn't say I've ever experienced an incident that could be defined as acoustic shock.

The first time I ever got hyperacusis it was gradual and then I think one loud event (an acoustic trauma I would say as opposed to an acoustic shock) exacerbated my symptoms. I had the classic burning/searing pain in ears, hot/cool sensations, aural fullness and trigeminal pain. This second time was also triggered by an event/series that was overly loud (although it didn't feel it in the moment). The first time was more gradual + acoustic trauma and the second time was acoustic trauma (although I already had a 'damaged cochlea' so the threshold for re-activation was lower). Both times the symptoms I experienced were very similar - hot/cool sensations in ears, burning searing pain, aural fullness. This second time I experienced more trigeminal pain but even that has practically gone now.

Some of the worst stories I have read are the ones on the Hyperacusis Research website under Patient Stories - cases where people experience severe intractable chronic pain that is very slow to improve. I have read many of these and something I have noted is that many of them started off with a history of loud noise exposure and then reached a threshold where the damage tipped over into hyperacusis/tinnitus territory. So I suspect hearing loss is the ultimate underlying pathology in leading to all these bizarre auditory symptoms.

Another thing I noticed in many of these case stories is that the medical help they were given often ended up worsening them and causing further setbacks - so if your ears are already very sensitised and you're just told to 'push through it' then I can see how that would ultimately lead to severe chronic pain with the ears not getting the chance to properly recover. I think if you view it similarly to any other injury e.g. a knee injury you have to give it time to heal properly so I think some of the very severe cases are repeated noise traumas. But then you have cases like Cindy Redmond's, a young teen, where she had an airhorn (130dB!) blasted into her ear - I mean, this probably flattened some OHCs. So I don't really think gradual vs non-gradual matters too much but I think they all originate from some sort of hearing loss.

I think the research team are Johns Hopkins are studying the Type 2 activation in mice. The theory is that once the OHCs are damaged the type 2s become easier to activate which makes sense - one question I have is why does that initiation threshold vary so much between different people? Every noxacusis sufferer is different it seems where for some people the type 2s are activated practically at the threshold of hearing whereas for others it would take something like a loud bar or a cinema.
 
#10,300
Diesel said:
I'm starting to question the use of "acoustic shock/trauma" as being anything other than really "fast" NIHL. It seems to be thrown around like its a special cause of hearing loss; and somehow those who experienced it will need some special treatment. Where really, it's just same old cell death/damage happening really quickly.

Acoustic shock sometimes does and does not cause hyperacusis; other than it being a faster way to lose hearing, what makes it any more unique than gradual NIHL?

The great news is, there has never been a for-fact "NO it won't help..." but here's a helpful theory:

There seems to be a fair amount of agreement that OHC damage/death are related with several symptoms associated with hyperacusis. Enough OHC damage/death associated with their respective Type-II nerve may be triggering many of these symptoms.

FX-322 causes progenitors to regenerate OHC that are damaged, dead or missing. Called Progenitor Cell Activation (PCA).

When PCA occurs. The brand-new OHC are also reconnected to the appropriate nerve; the Type-II nerve in this case. The same way it was done in the womb; as nature intended.

It stands to reason with a fresh batch of new, living OHC connected to the Type-II nerve, symptoms related to hyperacusis would begin to fade or at least be reduced over time.

I, for one, will be looking closely at the results of the Hearing Handicap and Quality-of-Life survey data from the Phase 2A. Certainly some of the 96 participants have hyperacusis; they all will have significant hearing loss for starters, so prevalence of tinnitus and hyperacusis should be higher than "normal." Considering how greatly hyperacusis affects QOL, I would expect those scores to significantly improve post FX-322.
Click to expand...
I agree with this - we're now starting to learn that the cochlea is far more vulnerable to damage than previously thought. According to hyperacusis.net acoustic shock is defined as "any sound that is perceived as threatening, usually a sudden/unexpected/loud sound heard near the ear. The sound is rarely loud enough or present for long enough to cause a noise induced hearing loss." But we now know that current methods to diagnose hearing loss are primitive - perhaps acoustic shock doesn't typically show up on a normal audiogram but it causes EHF loss or synapse loss, who knows?

I think noxacusis/acoustic shock in general can be seen as a bit of an extra special edge case disorder but I'm not sure, I have a gut feeling it's all linked to hearing loss fundamentally.

I've also seen this view expressed occasionally here that FX-322 won't help hyperacusis as Frequency Therapeutics haven't mentioned hyperacusis in any of their discussions about the drug. The way I see it, they're not purposefully omitting any mention of it because they believe it won't work for hyperacusis. I think it's more that hearing loss and tinnitus are far more common and well-known, both amongst the public and medical professionals. I always forget that outside of this forum and some research circles hyperacusis, and more specifically noxacusis is pretty unknown. I mean, I've seen figures that estimate its prevalence at 1 in 50,000 - Bryan Pollard said in his Tinnitus Talk Podcast interview that it's difficult to increase awareness when even doctors report that they may only see a handful of cases per year of disabling hyperacusis. Even experienced clinicians at major hospitals seem dumbfounded at the concept of noise-induced pain, in some cases. It took Cindy Redmond 6 months to get a diagnosis. The clinical world is far behind the research.

I also think, from a commercial standpoint, Frequency Therapeutics are really focused on meeting the needs of a significant 'unmet market' - hearing loss is extremely common and tinnitus too. I'm not necessarily alarmed by hyperacusis not factoring much into their discussions at the moment as it's not really a 'significant market' - but I think it will be interesting to see whether this will emerge as the trials progress. Not sure if that makes sense, just my take.
 
#10,301
serendipity1996 said:
I agree with this - we're now starting to learn that the cochlea is far more vulnerable to damage than previously thought. According to hyperacusis.net acoustic shock is defined as "any sound that is perceived as threatening, usually a sudden/unexpected/loud sound heard near the ear. The sound is rarely loud enough or present for long enough to cause a noise induced hearing loss." But we now know that current methods to diagnose hearing loss are primitive - perhaps acoustic shock doesn't typically show up on a normal audiogram but it causes EHF loss or synapse loss, who knows?

I think noxacusis/acoustic shock in general can be seen as a bit of an extra special edge case disorder but I'm not sure, I have a gut feeling it's all linked to hearing loss fundamentally.

I've also seen this view expressed occasionally here that FX-322 won't help hyperacusis as Frequency Therapeutics haven't mentioned hyperacusis in any of their discussions about the drug. The way I see it, they're not purposefully omitting any mention of it because they believe it won't work for hyperacusis. I think it's more that hearing loss and tinnitus are far more common and well-known, both amongst the public and medical professionals. I always forget that outside of this forum and some research circles hyperacusis, and more specifically noxacusis is pretty unknown. I mean, I've seen figures that estimate its prevalence at 1 in 50,000 - Bryan Pollard said in his Tinnitus Talk Podcast interview that it's difficult to increase awareness when even doctors report that they may only see a handful of cases per year of disabling hyperacusis. Even experienced clinicians at major hospitals seem dumbfounded at the concept of noise-induced pain, in some cases. It took Cindy Redmond 6 months to get a diagnosis. The clinical world is far behind the research.

I also think, from a commercial standpoint, Frequency Therapeutics are really focused on meeting the needs of a significant 'unmet market' - hearing loss is extremely common and tinnitus too. I'm not necessarily alarmed by hyperacusis not factoring much into their discussions at the moment as it's not really a 'significant market' - but I think it will be interesting to see whether this will emerge as the trials progress. Not sure if that makes sense, just my take.
Click to expand...
Completely agree with the marketability of hyperacusis when compared to hearing loss and tinnitus, which are both well known and understood in comparison.

I also cannot find a universally/generally accepted or standard by which hyperacusis is measured in the clinical and research setting. There are proposals for measuring hyperacusis, but nothing that is validated like the TFI, for example. The other troubling reason is that there is unclear agreement by what hyperacusis actually is... is it pain? loudness? just fear of sound?

This may be the simple reason Frequency Therapeutics doesn't mention it. They can't quantify it using a standard test that either the FDA or clinicians are willing to accept as an outcome. In the Phase 2A for example, all of their tests are accepted by clinicians, the FDA, or insurance as a standard measure of a drug's effectiveness.

It may very will be that tinnitus treatment and hyperacusis/noxacusis treatments coincide... so if the patient is treated for tinnitus with FX-322, it benefits in reducing hyperacusis as well.
 
#10,302
Diesel said:
This may be the simple reason Frequency Therapeutics doesn't mention it. They can't quantify it using a standard test that either the FDA or clinicians are willing to accept as an outcome.
Click to expand...
Yeah this is correct.

If it weren't for the TFI then tinnitus wouldn't have been included in the phase 2a trial data collection. Frequency Therapeutics did standard tests for the first phase and saw that there was some efficacy so they decided to explore extended audiograms in phase 2a. They also heard some anecdotal evidence of tinnitus improvement so they included the TFI as well.

I'm sure they did it this way not to jeopardize the beginnings of the trial since this is primarily a hearing loss drug. Also, hearing loss is much more quantifiable because of audiograms and speech-in-noise tests, so I'm sure any regeneration drug will first explore these more quantifiable tests and will then explore how it affects tinnitus in later studies.

This is why I think drugs solely targeting tinnitus are generally going to be less successful. You almost need an ulterior motive first, like hearing loss or in the case of Neuralink, calling your Tesla with your brain (jk lol), in order to have a better chance of reaching the later stages of trials. We really need an objective measurement for tinnitus (and also hyperacusis).
 
#10,303
FGG said:
I think almost everyone agrees it will help loudness hyperacusis as much as tinnitus.
Click to expand...
I do believe that restoring OHCs will help with both pain and loudness hyperacusis.

The reason why I say this is that those who suffer from loudness hyperacusis may also suffer from pain hyperacusis but at higher dB level, yet lower dB levels compared to normal people.
 
#10,304
Danad said:
I am reposting this link and excerpt supporting the notion that regenerating OHCs will help with hyperacusis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383716/
Click to expand...
Pardon me for jumping in here, but the highlighted excerpt you linked doesn't actually apply to the A2 fibers. That specific Liberman paper from 1984 is about how OHC destruction can cause enough downward energy to damage the IHC and A1 fibers via the tectorial membrane. This is, to my knowledge, one of the first mechanical explanations behind noise-induced synaptopathy as we know it today.

I'm also familiar with the papers cited in the unhighlighted portions, and those too involve A1 synaptopathy, not the A2 fibera stimulated in noxacusis. If anyone wants to do a double-check, feel free - I might have missed a noxacusis mention.

I say this not to invalidate the theories behind OHC restoration possibly resolving noxacusis, but only to clarify that those papers involved loudness hyperacusis, not pain.

Edit: Just wanted to add that he later refined this to show that the same mechanical energy can deplete A1 fibers even without OHC damage. Hence the whole "hidden hearing loss" thing.
 
#10,305
Can I humbly request on this thread that anytime hyperacusis is mentioned, people clarify if they mean loudness or noxacusis? It would be way less confusing.
 
#10,306
patorjk said:
Also, as an interesting aside, while researching this, I came across a foreign language hearing loss forum and saw posts referring to this thread. There are people who use google translate to read this thread and keep up with FX-322. It was a little surreal, it's like we're in a fishbowl. It made me wonder how many lurkers this thread has.
Click to expand...
Many, you can count on it. I spend time at the Acoustic Guitar Forum and one popular thread currently has 52 comments and around 1,100 views.
 
#10,307
Diesel said:
I'm starting to question the use of "acoustic shock/trauma" as being anything other than really "fast" NIHL. It seems to be thrown around like its a special cause of hearing loss; and somehow those who experienced it will need some special treatment. Where really, it's just same old cell death/damage happening really quickly.

Acoustic shock sometimes does and does not cause hyperacusis; other than it being a faster way to lose hearing, what makes it any more unique than gradual NIHL?
Click to expand...
@Diesel, I agree with the OHC theory. It's the one I most want to be true but regarding noxacusis as a result of acoustic shock, I'm going to expand on it a bit. I also agree that acoustic shock causes NIHL at a rapid pace, but I believe acoustic shock causes far more damage than just NIHL. I hang onto these 3 possibilities below.

1. Type II afferents are activated when outer hair cells are damaged and cause noxacusis. Fix the OHCs with FX-322 and then in theory connections and sensory input are restored. FX-322 is potentially the full fix for noxacusis sufferers who didn't get it through acoustic shock.

This is also good to know (quoted from the link below) 'Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage'. So the new retigabine is also a possibility I hope. https://www.pnas.org/content/112/47/14723

2. Based on the acoustic shock symptoms cluster, the point that stands out for me is the devastating chain reaction of inflammatory and destructive processes that get kicked off at the outset of the shock, only one of which is possibly the destruction of OHC's and sensitization of type II's. Notable points below are taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

'The middle ear inflammation [resulting from the acoustic shock] is associated with the secretion of many proinflammatory molecules and may lead to earache and otalgia (tingling and stabbing pain).'

'To note, the inflammatory molecules present in the middle ear cavity may cross the round window and cause inner ear damages (hearing loss), in particular in the high frequency region. One can further speculate that these molecules (such as ATP) may further reach the organ of Corti and activate the unmyelinated type II afferent neurons synapsing with OHC'.

'Finally, ATP and other proinflammatory molecules, produced in the middle ear during inflammatory processes and diffusing up to the Organ of Corti, may activate cochlear type II fibers and trigger sound-induced earache. One notes that ATP may also be released by the OHCs that are damaged due to the acoustic shock or trauma or due to the cytotoxic effects of proinflammatory molecules that diffused from the middle ear. Assuming that the diffusion of ATP secreted in the middle ear is limited to the cochlear base, sound-induced earache may be produced by high-frequency sound, which is consistent with informal patient reports.'

'Tinnitus that follows an acoustic trauma has been reported to fluctuate over time, in close correlation with tingling in the ear and otalgia' (Noting this because it exactly matches my tinnitus / hyperacusis relationship).

Here's the important bit where I'm a bit more skeptical about FX-322. It could break the cycle by repairing OHC's, and certainly could deal with some otalgia, but if any other resulting nerve pain (from the acoustic shock, not the type II's) remains ongoing due to being a separate self sustaining process then I think a separate nerve pain management drug is also needed. The link above goes deep, but from what I can relate to in it, and regarding your question 'what makes it any more unique than gradual NIHL?' I'd say the answer is that many more independent sensitization's of different nerve systems appear to take place during an acoustic shock. NIHL is only one single offshoot of the cluster of symptoms. My biggest question in this scenario should I only take FX-322, is would any nerve pain still present be sensitive to noise any more? I might be happier that even though there was still various nerve pain left, at least now it might not be noise sensitive anymore.

3. Synapse disconnection. Hopefully OTO, Hough or Pipeline could also potentially be a fix if this causes noxacusis.

There are more theories that involve genetics and the fact that some people may be more predisposed to noxacusis, but until I can ever try these drugs It's enough for me now to have faith in them working and in my genetics.

Bottom line is, no one knows, I could be wrong about everything, but it doesn't hurt to try and do a bit of working out. I'm not negative about any of these drugs, they all sound promising. I'm trying to (with what precious little knowledge we have) build up hope that what's in the research pipeline will benefit noxacusis sufferers in as many of the various scenarios as possible because we need some hope. I have far more hope for solely hearing loss and tinnitus sufferers. If I was suffering from either or both of those conditions without noxacusis then I'd be confidently waiting for the upcoming drugs.

I like your posts, I read lots of them but respectfully, this one quoted was out of place seeing as you're on here obviously as a sufferer of something hearing related. I don't think it's fair to say with regard to acoustic shock 'It seems to be thrown around like it's a special cause of hearing loss; and somehow those who experienced it will need some special treatment.' This just sounds like you personally are bored of hearing the term and it comes across as dismissive. It could almost be something I'd expect from a doctor. I'm pointing this out in the friendliest way possible, I'm not aware of what you suffer from, but this is what I suffer from.

Acoustic shock leading to life changing noxacusis is a horrific and instantaneous turning point in someone's life. There's nothing gradual about it, and it does not get thrown around lightly. I've spent most of the last several years in pain, in bed, in silence, reading about all the potential upcoming drugs for hearing loss and tinnitus wondering where the F*** does pain hyperacusis come into the picture. One of the only things I have left in life is to read what I can and try and decipher the web of the potential causes, pathologies, symptoms, and treatments to fit noxacusis into the equation, luckily after lots of reading and very helpful input from here I'm optimistic and I think one way or another, as long as the drugs get successfully released, noxacusis will be covered. I hope this offers a little bit of optimism anyway.
 
#10,308
100Hz said:
@Diesel, I agree with the OHC theory. It's the one I most want to be true but regarding noxacusis as a result of acoustic shock, I'm going to expand on it a bit. I also agree that acoustic shock causes NIHL at a rapid pace, but I believe acoustic shock causes far more damage than just NIHL. I hang onto these 3 possibilities below.

1. Type II afferents are activated when outer hair cells are damaged and cause noxacusis. Fix the OHCs with FX-322 and then in theory connections and sensory input are restored. FX-322 is potentially the full fix for noxacusis sufferers who didn't get it through acoustic shock.

This is also good to know (quoted from the link below) 'Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage'. So the new retigabine is also a possibility I hope. https://www.pnas.org/content/112/47/14723

2. Based on the acoustic shock symptoms cluster, the point that stands out for me is the devastating chain reaction of inflammatory and destructive processes that get kicked off at the outset of the shock, only one of which is possibly the destruction of OHC's and sensitization of type II's. Notable points below are taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

'The middle ear inflammation [resulting from the acoustic shock] is associated with the secretion of many proinflammatory molecules and may lead to earache and otalgia (tingling and stabbing pain).'

'To note, the inflammatory molecules present in the middle ear cavity may cross the round window and cause inner ear damages (hearing loss), in particular in the high frequency region. One can further speculate that these molecules (such as ATP) may further reach the organ of Corti and activate the unmyelinated type II afferent neurons synapsing with OHC'.

'Finally, ATP and other proinflammatory molecules, produced in the middle ear during inflammatory processes and diffusing up to the Organ of Corti, may activate cochlear type II fibers and trigger sound-induced earache. One notes that ATP may also be released by the OHCs that are damaged due to the acoustic shock or trauma or due to the cytotoxic effects of proinflammatory molecules that diffused from the middle ear. Assuming that the diffusion of ATP secreted in the middle ear is limited to the cochlear base, sound-induced earache may be produced by high-frequency sound, which is consistent with informal patient reports.'

'Tinnitus that follows an acoustic trauma has been reported to fluctuate over time, in close correlation with tingling in the ear and otalgia' (Noting this because it exactly matches my tinnitus / hyperacusis relationship).

Here's the important bit where I'm a bit more skeptical about FX-322. It could break the cycle by repairing OHC's, and certainly could deal with some otalgia, but if any other resulting nerve pain (from the acoustic shock, not the type II's) remains ongoing due to being a separate self sustaining process then I think a separate nerve pain management drug is also needed. The link above goes deep, but from what I can relate to in it, and regarding your question 'what makes it any more unique than gradual NIHL?' I'd say the answer is that many more independent sensitization's of different nerve systems appear to take place during an acoustic shock. NIHL is only one single offshoot of the cluster of symptoms. My biggest question in this scenario should I only take FX-322, is would any nerve pain still present be sensitive to noise any more? I might be happier that even though there was still various nerve pain left, at least now it might not be noise sensitive anymore.

3. Synapse disconnection. Hopefully OTO, Hough or Pipeline could also potentially be a fix if this causes noxacusis.

There are more theories that involve genetics and the fact that some people may be more predisposed to noxacusis, but until I can ever try these drugs It's enough for me now to have faith in them working and in my genetics.

Bottom line is, no one knows, I could be wrong about everything, but it doesn't hurt to try and do a bit of working out. I'm not negative about any of these drugs, they all sound promising. I'm trying to (with what precious little knowledge we have) build up hope that what's in the research pipeline will benefit noxacusis sufferers in as many of the various scenarios as possible because we need some hope. I have far more hope for solely hearing loss and tinnitus sufferers. If I was suffering from either or both of those conditions without noxacusis then I'd be confidently waiting for the upcoming drugs.

I like your posts, I read lots of them but respectfully, this one quoted was out of place seeing as you're on here obviously as a sufferer of something hearing related. I don't think it's fair to say with regard to acoustic shock 'It seems to be thrown around like it's a special cause of hearing loss; and somehow those who experienced it will need some special treatment.' This just sounds like you personally are bored of hearing the term and it comes across as dismissive. It could almost be something I'd expect from a doctor. I'm pointing this out in the friendliest way possible, I'm not aware of what you suffer from, but this is what I suffer from.

Acoustic shock leading to life changing noxacusis is a horrific and instantaneous turning point in someone's life. There's nothing gradual about it, and it does not get thrown around lightly. I've spent most of the last several years in pain, in bed, in silence, reading about all the potential upcoming drugs for hearing loss and tinnitus wondering where the F*** does pain hyperacusis come into the picture. One of the only things I have left in life is to read what I can and try and decipher the web of the potential causes, pathologies, symptoms, and treatments to fit noxacusis into the equation, luckily after lots of reading and very helpful input from here I'm optimistic and I think one way or another, as long as the drugs get successfully released, noxacusis will be covered. I hope this offers a little bit of optimism anyway.
Click to expand...
I find the appearance of any type of hyperacusis, or the complete lack thereof, after an acoustic trauma confusing. Some with an acoustic shock or trauma get no hyperacusis at all and some get it horrifically, yet those without can still have horrific tinnitus.

Either way, I hope that by fixing the underlying damage we all see improvement in all our symptoms. At least those with (suspected) hearing loss as this obviously won't work for some other causes.
 
#10,309
100Hz said:
I like your posts, I read lots of them but respectfully, this one quoted was out of place seeing as you're on here obviously as a sufferer of something hearing related. I don't think it's fair to say with regard to acoustic shock 'It seems to be thrown around like it's a special cause of hearing loss; and somehow those who experienced it will need some special treatment.' This just sounds like you personally are bored of hearing the term and it comes across as dismissive. It could almost be something I'd expect from a doctor. I'm pointing this out in the friendliest way possible, I'm not aware of what you suffer from, but this is what I suffer from.
Click to expand...
I greatly appreciate your thoughtful and thorough response to my discussion regarding hyperacusis and noxacusis as it relates to acoustic trauma and FX-322. I definitely did not intend to sound dismissive of the effects of an acoustic trauma, or anyone living with hyperacusis and noxacusis. I actually do live with all three, tinnitus, hyperacusis and intermittent noxacusis, and my journey started with an unfortunate acoustic trauma from an untimely tool malfunction. Many of the symptoms described in #2 of your response I lived with for about 6 months, which I assume is more noxacusis than hyperacusis. Fortunately now, it's become much more manageable, but there are times where it sneaks up and lingers for a few days from some random event.
 
#10,310
There is some very thought-provoking discussion here. I think with noxacusis there's lots of questions as to whether there is also middle ear vs inner ear pathology. Jaime-Garcia Anoveros from Northwestern did some experiments in mice on this a few a years ago, in an attempt to determine which parts of the auditory system respond to noxious noise. His conclusion was that this response originates in the cochlear inner ear.

From the 2016 ARO Auditory Nocicpetion and Pain Hyperacusis Symposium notes:
"In mice without Vglut3, Jaime found significant responses to noxious noise (120dB), which damages hair cells, but not to innocuous noise (80dB), by neurons of the cochlear nucleus, but not of the vestibular or trigeminal nuclei. Noxious noise activated neurons in the cochlear nucleus in a pattern consistent with the innervation of Type II afferents. Some areas of the cochlear nucleus activated were different than normal auditory responses. The response to noxious noise originates in the cochlea and not in other areas also stimulated by intense noise (middle ear and vestibule), as the response was absent in another type of mutant mice with selective cochlear degeneration but normal vestibular and somatosensory function."
https://hyperacusisresearch.org/2016-aro-symposium-pain-hyperacusis/

But then the model put forth in that paper on acoustic shock is also very intriguing - since acoustic shock seems to be characterised by a very sudden and unexpected noise, could there be a different sort of response when the noise is perceived as a shock? I just wish we knew exactly what's going on!
 
#10,314
I enjoy the discussions between the high knowledge users; this is helpful for people with brain fog and focusing problems. Also, I don't mind the talk about stock market suggestions. Let's be honest, it would be pretty cool to come out of this experience making money on an investment. I realize this is unlikely to become a dream scenario, but it's interesting to think about.
 
#10,316
Paulmanlike said:
David Lucchino today disposed of just over 15,000 shares but appears to be part of a rule 10b5-1 trading plan. Nothing to worry about, right, @Diesel, @FGG?
Click to expand...
Well, he's blinded to the trial so we know it's not the drug. If anything he's reading the writing on the wall for the entire biotech sector which is not looking good at all.
 
#10,317
Long time lurker on this thread as, like all of you very much hoping FX-322 can come through for us tinnitus suffers. I had a very simple question (and apologies for interrupting the flow of a very interesting discussion). If the theory is that tinnitus may improve by restoring hearing in the same frequency ranges as the tinnitus itself, why would this be any different to a hearing aid that had the capability to do the same thing?

I had become reasonably accustomed to my 'mid-level' tinnitus until very recently when an accidental one-off noise exposure has sent it sky high. I'm hoping it'll settle back down to something more manageable, but if not wondering if a good quality hearing aid is worth considering. My hearing loss is from 2 kHz and up, and my tinnitus seems to be in the 7-8 kHz range (hard to tell exactly because it's not a pure tone, but definitely in the higher ranges).

Thanks in advance,
Paul

P.S. I did contact one of the FX-322 test centers this week and was told that they just filled the 96 person trial for the phase 2 testing and have closed enrollment on Monday.
 
#10,319
ploughna said:
Long time lurker on this thread as, like all of you very much hoping FX-322 can come through for us tinnitus suffers. I had a very simple question (and apologies for interrupting the flow of a very interesting discussion). If the theory is that tinnitus may improve by restoring hearing in the same frequency ranges as the tinnitus itself, why would this be any different to a hearing aid that had the capability to do the same thing?

I had become reasonably accustomed to my 'mid-level' tinnitus until very recently when an accidental one-off noise exposure has sent it sky high. I'm hoping it'll settle back down to something more manageable, but if not wondering if a good quality hearing aid is worth considering. My hearing loss is from 2 kHz and up, and my tinnitus seems to be in the 7-8 kHz range (hard to tell exactly because it's not a pure tone, but definitely in the higher ranges).

Thanks in advance,
Paul

P.S. I did contact one of the FX-322 test centers this week and was told that they just filled the 96 person trial for the phase 2 testing and have closed enrollment on Monday.
Click to expand...
I would consider a good quality hearing aid in the meantime. Hearing aids amplify sound which is only one component of hearing but it sounds like your tinnitus is in a range where they have the potential to improve it. At least in the US, most places will let you trial a hearing aid for 30 days before you buy it. It's definitely worth a shot!
 
#10,320
ploughna said:
Long time lurker on this thread as, like all of you very much hoping FX-322 can come through for us tinnitus suffers. I had a very simple question (and apologies for interrupting the flow of a very interesting discussion). If the theory is that tinnitus may improve by restoring hearing in the same frequency ranges as the tinnitus itself, why would this be any different to a hearing aid that had the capability to do the same thing?

I had become reasonably accustomed to my 'mid-level' tinnitus until very recently when an accidental one-off noise exposure has sent it sky high. I'm hoping it'll settle back down to something more manageable, but if not wondering if a good quality hearing aid is worth considering. My hearing loss is from 2 kHz and up, and my tinnitus seems to be in the 7-8 kHz range (hard to tell exactly because it's not a pure tone, but definitely in the higher ranges).

Thanks in advance,
Paul

P.S. I did contact one of the FX-322 test centers this week and was told that they just filled the 96 person trial for the phase 2 testing and have closed enrollment on Monday.
Click to expand...
Thanks for letting us know. This is great news that 96 participants have been filled. Hopefully results don't get delayed and are still coming out in April.
 

Log in or register to get the full forum benefits!

Register

Register on Tinnitus Talk for free!

Register Now
Top Bottom
Back
Forums
Members
Donate
Menu