Frequency Therapeutics — Hearing Loss Regeneration

I have good hearing up to 8000 Hz according to various audiograms. I have tinnitus with different tones and a very strong case of noxacusis.

Is it possible that I have profound hearing loss in frequencies above 8000 Hz? Could I have lost support cells in the high frequencies? How can I find out?
I would be surprised if you had not tried this yet.

If your curiosity gets the best of you while you're waiting for a real extended test -
You can do a rudimentary self-test of your high frequency hearing using your phone or computer.

Go onto YouTube or browser and type in 10 kHz.
Start there and go up to 14 kHz.

Just be vigilant about volume levels and keep the speaker arm distance from your ears.

Also - don't do this often or for long periods of time.
I'm sure it can be unsafe if you're not sensible about it.
 
Noxacusis involves different synapses (type 2 afferent neurons, which are pain fibers, and their synapses on the OHC). I don't see how this drug would make that worse, personally.
Does this mean then that FX-322 probably won't help us hyperacusis sufferers?

If I recall correctly, one researcher recently described that the extra synaptic ribbons resulting from acoustic trauma (in cases where hyperacusis is also suspected to occur) as being a case of "maladaptive plasticity".

How then would new OHCs (and their respective synapses), in the form of increased input, reverse this maladaptive plasticity?

My understanding of the word plasticity here is one of malleability - and therefore reversibility - so does that mean that these extra synaptic ribbons might "die off" once the cochlea detects new OHCs? I'm just struggling to understand how we can be cured of hyperacusis in the continued presence of these extra synapses, even if our hearing has improved.
 
Does this mean then that FX-322 probably won't help us hyperacusis sufferers?

If I recall correctly, one researcher recently described that the extra synaptic ribbons resulting from acoustic trauma (in cases where hyperacusis is also suspected to occur) as being a case of "maladaptive plasticity".

How then would new OHCs (and their respective synapses), in the form of increased input, reverse this maladaptive plasticity?

My understanding of the word plasticity here is one of malleability - and therefore reversibility - so does that mean that these extra synaptic ribbons might "die off" once the cochlea detects new OHCs? I'm just struggling to understand how we can be cured of hyperacusis in the continued presence of these extra synapses, even if our hearing has improved.
My response was that I don't see any way for it to make it worse.

As far as making it better, it's possible.

Noxacusis seems to be multi factorial and involve ATP leakage (from both damaged OHCs and tight junctions). If you regenerate damaged hair cells, then this would at least reduce this contribution. The tight junction leakage is more inflammatory in nature so you would need to address that, too.

But then you have the added factor of pain fiber sensitization, which does involve the purine receptors (among other things), so they might normalize more without extra ATP binding to them.

As far as the extra OHC/afferent pain fiber synapses that are unique to noxacusis, this has only--thus far--been shown to occur in rodents. So we have no idea how that will affect humans, if at all.

If those "extra synapses" are a form of plasticity in humans as well (again *if*, no one knows), then I suspect it's not permanent because people can and do recover from noxacusis with time. I think whatever does work for noxacusis won't be immediate (unless it's a Nav channel blocker which will block pain) as it will take time to reverse the sensitization.
 
I would be surprised if you had not tried this yet.

If your curiosity gets the best of you while you're waiting for a real extended test -
You can do a rudimentary self-test of your high frequency hearing using your phone or computer.

Go onto YouTube or browser and type in 10 kHz.
Start there and go up to 14 kHz.

Just be vigilant about volume levels and keep the speaker arm distance from your ears.

Also - don't do this often or for long periods of time.
I'm sure it can be unsafe if you're not sensible about it.
I wouldn't recommend doing this with YouTube due to compression. I've found I can never hear above 15 kHz from anything on YouTube and it's not because of my hearing range, it's due to YouTube compression.

Download Audacity and generate a sine wave. That will be enough to test. When I do this and test all of the frequencies I can hear up to 21 kHz before it drops off.
 
This theory of yours seems entirely plausible. Prior to November 2020, for the last 6 years or so, I had what I would call a "quiet" high pitched tinnitus on my left side where I would not notice it unless I was specifically listening for it and the room was VERY quiet. I could increase the tinnitus just by clenching my teeth together. That's how I could gauge how bad it was - I would compare clenching teeth to no clenching of teeth, and would always be satisfied that the tinnitus was still the same "quiet" volume in my head. Entirely manageable and not intrusive at all.

Well, about a month ago I experienced a loud traumatic event - my ears felt full for 3 or 4 days, I thought I came down with a sinus infection or something. I had no idea the fullness in my ear, the dampening of all sounds was related to hearing loss. Boy, was I in for a nice surprise about 4 to 7 days later... I can't be sure of the timeline... it just started up late one night and has not gone away... now I have it in BOTH ears, about 2x louder than before and ALWAYS noticeable, even when talking... it's driving me up the wall. Now it's the SAME loudness as when I clench my teeth, but at a slightly different frequency (that's the only way I can tell the sounds apart). I have to literally always be doing something, which is exhausting, in order to try and forget about it. Thoughts of hanging myself now cross my mind, it's torture. On a scale of 1 to 10 prior to the loud event, the tinnitus was perhaps a 1, maybe 2 out of 10. Now it's in the 6 to 7 range of severity, as it has crossed over to both ears, with varying frequency and intensity and I can always hear it.

Perhaps there are some interesting points I can make about my particular case. I lost some high frequency hair cells in my teens from listening to headphones and hard rock too much. I remember my ears would feel hot and numb for 20 minutes or so after listening for prolonged periods (45 minutes to 1 hour). I never had any tinnitus (yet).

Then as I grew older my stress levels increased and I didn't sleep very well - my sleep/wake cycles were all messed up for nearly a decade. I didn't listen to headphones as much anymore, BUT I took dance lessons for years, and wore ear plugs for perhaps 70% of the time (when I remembered them) - the other 30% of the time I would take some chewing gum and stick it in my ears so they didn't hurt. Hard to find earplugs at 1am.

Thinking back to when I was a child my ears were always super sensitive to loud sounds... the school bell would make my ears hurt and I would have to cover my ears. I was born premature by 4 weeks. Already seem to be setting myself up for tinnitus while in an incubator in the 1970's.

Fast forward to my mid-forties (2015) and tinnitus starts to creep into my left ear. I am now careful to wear earplugs everywhere I go - theme park, concerts, outdoor events with big speakers... I had to wear earplugs around my children as well. Ear plugs at the local park. I could not take the pain of loud sounds - anything over 90 dB (I measured it) and it's as if my hearing clipped and plugged up. Hyperacusis? I guess so. I've had it for so long, I actually thought it was normal for everyone to feel the pain of loud sounds. Boy was I stupid. I never asked anyone about it.

Fast forward to November 2020, all it took was ONE loud event, no ear plugs, and boom... my auditory system gets taken over the edge... almost like a cytokine storm... Now what's very interesting is that the loud event was very low frequency... enough to shock the cilia in my ears... so it most likely killed cilia that were already on the verge of dying within the next 10 years... but this noise just accelerated their death... that's what I think. Or I just ended up killing more hair fibers. Can fibers partially work? Who knows.

The way I see it - since I already had some hearing loss... regardless of how little... plus mild tinnitus already... plus the added stresses in life... plus a poor diet and lack of exercise... I basically set my neurological system up for failure... it was not resilient enough to cope with adverse auditory events. I also suffered from joint pains, 10 year old injuries would still hurt, small injuries would take forever to heal or not heal at all, and nobody could figure out why. Medical establishment was useless. I suffered pains all over my body.

I bet restoring even a few of my missing hair cells would reduce the tinnitus back to some manageable level... I will take 10% to 20% reduction any day over nothing. When I look at that graph you posted, I see myself in the red line... and I believe I can get back to the green line. That would be a miracle. I would cut off my little finger if that's all it took.
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.
 
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'm sorry, this made me laugh out loud. Thanks for that. :LOL:

I'm suffering a similar spike/worsening right now... the noxacusis and reactivity is through the roof. ALL sounds hurt. Oddly enough the tinnitus is pretty much unaffected. I'm 8 weeks in without any improvement. It gives me some hope that yours got at least slightly better... I'm praying for "slightly better" right now...

Thanks @FGG for your answer about hyperacusis and FX-322, also gives me hope!
 
I'm sorry, this made me laugh out loud. Thanks for that. :LOL:

I'm suffering a similar spike/worsening right now... the noxacusis and reactivity is through the roof. ALL sounds hurt. Oddly enough the tinnitus is pretty much unaffected. I'm 8 weeks in without any improvement. It gives me some hope that yours got at least slightly better... I'm praying for "slightly better" right now...

Thanks @FGG for your answer about hyperacusis and FX-322, also gives me hope!
I didn't notice any improvement really until 4-5 months. Hope you improve!

Also I'm glad it was funny but I'm completely serious. I basically told my family if it didn't improve I would be opting out of existence. I went on disability from my job for 3 months. I also stayed in a hotel for a month in near total silence because anything would spike it, and I have not really left my home in the last three months - I have food delivered and due to COVID-19 work from home.

I don't want to jinx it but I've been enjoying the last few weeks rather than suffering every minute.
 
I didn't notice any improvement really until 4-5 months. Hope you improve!

Also I'm glad it was funny but I'm completely serious. I basically told my family if it didn't improve I would be opting out of existence. I went on disability from my job for 3 months. I also stayed in a hotel for a month in near total silence because anything would spike it, and I have not really left my home in the last three months - I have food delivered and due to COVID-19 work from home.

I don't want to jinx it but I've been enjoying the last few weeks rather than suffering every minute.
Yeah, sorry, I know you're serious. I just couldn't help my morbid humour for a second. It's an F'ing nightmare, I know. I've seriously been considering going on disability, but luckily I'm a video editor and can do about 50% of my work from home and I think I can continue to do that. The other half I'm usually doing on-site at motorsport events... go figure... The next one is not until May though, so I guess we'll see where I'm at then.

Being around anyone and having to talk/listen is extremely exhausting and painful atm, so yeah, alone at home is my preferred setting right now.
 
Sorry, I might have misinterpreted because I had read people saying that tinnitus is always from hearing loss (unless from some other identifiable cause) and that restoring hearing is enough to cure tinnitus. Which I don't believe is the case at all.

Reading back I feel I was upset and a bit emotional in my judgment.

Sorry, and Merry Christmas everyone!
 
Sorry, I might have misinterpreted because I had read people saying that tinnitus is always from hearing loss (unless from some other identifiable cause) and that restoring hearing is enough to cure tinnitus. Which I don't believe is the case at all.

Reading back I feel I was upset and a bit emotional in my judgment.

Sorry, and Merry Christmas everyone!
Tinnitus is caused by many different things like hearing loss, ototoxic medication, benzo withdrawal, head trauma, and more. Some of these are neurological while some are cochlear. FX-322 is being developed for sensorineural hearing loss, so hair cells. The theory is that tinnitus is a phantom ringing being caused by lack of input to the brain. Theoretically if we restored the damage that started the phenomenon then the brain would be neuroplastic enough to go back to normal.
 
Theoretically if we restored the damage that started the phenomenon then the brain would be neuroplastic enough to go back to normal.

I think we are all looking at this from the wrong side of the coin. Yes, restoring hearing would add input — but I think there's evidence that it's actually inhibitory input. Our ears are always 'on' (in a teleological sense). When we cone in on a sound, say middle C, we are able to hear that sound better — over the background noise — because, not only are there nerves firing 'middle C', but also because nerves, from those same hair cells, are inhibiting/dampening other tones. Think of it like software that's able to separate a single voice out of a cacophony of conversations — or how software is able to make blurry pictures sharper. Also, keep in mind that almost all synapses that form after we are born are inhibitory. This is why FX-322 seems to be good at improving conversation in noise — and why I think it'll help with hyperacusis — it will add regenerate the inhibitory input and turn down the noise.
 
Theoretically if we restored the damage that started the phenomenon then the brain would be neuroplastic enough to go back to normal.

I think we are all looking at this from the wrong side of the coin. Yes, restoring hearing would add input — but I think there's evidence that it's actually inhibitory input. Our ears are always 'on' (in a teleological sense). When we cone in on a sound, say middle C, we are able to hear that sound better — over the background noise — because, not only are there nerves firing 'middle C', but also because nerves, from those same hair cells, are inhibiting/dampening other tones. Think of it like software that's able to separate a single voice out of a cacophony of conversations — or how software is able to make blurry pictures sharper. Also, keep in mind that almost all synapses that form after we are born are inhibitory. This is why FX-322 seems to be good at improving conversation in noise — and why I think it'll help with hyperacusis — it will add regenerate the inhibitory input and turn down the noise.
I agree with this. I feel like somehow our ears are like a corrupted file and we need to use FX-322 to restore the program lol.
 
I wouldn't recommend doing this with YouTube due to compression. I've found I can never hear above 15 kHz from anything on YouTube and it's not because of my hearing range, it's due to YouTube compression.

Download Audacity and generate a sine wave. That will be enough to test. When I do this and test all of the frequencies I can hear up to 21 kHz before it drops off.
Not to mention the fact that there are also headphones etc which won't work with sounds above 16000 Hz either.
 
What about the eardrum perforation after being injected with FX-322?

Does the the hole in the eardrum heal afterwards? Will it be as good as before the injection?
 
I do not understand you. If you have tinnitus, you know for sure.
Some people have tinnitus so minor they don't realise it's tinnitus. Some have had it so long they think the noise IS silence.

That said, for the majority, they DO know when they have tinnitus. I periodically checked and looked for noise - especially if I heard electrical static. It was NEVER tinnitus, and always a real noise.

Now I do have tinnitus.
 
Some people have tinnitus so minor they don't realise it's tinnitus. Some have had it so long they think the noise IS silence.
This is actually something I have been pondering myself, and it's something I don't see often discussed here on Tinnitus Talk. I also find this as one of the most stressful things about experiencing these symptoms; have I had this all my life and am only just now finding it problematic? I suppose it could be the case that my sudden awareness is manifesting as a spike. It really makes me wonder how much of this is psychological.

I know that "true silence" isn't actually possible outside of the vacuum of space, but I am curious how those without tinnitus can hear nothing in a quiet place. I haven't bothered asking unafflicted friends and family to try this in fear that they will hear something and not let it go...
 
What about the eardrum perforation after being injected with FX-322?

Does the the hole in the eardrum heal afterwards? Will it be as good as before the injection?
In most cases, the ear drum heals fine. One member had about 80 protein rich plasma injections in his ear drums over a few weeks without complications.

Ear drum perforations (this usually refers to a larger than expected defect after injection) are uncommon and usually heal except in rare cases.

An ENT who is used to giving IT injections will dramatically minimize this risk (otologist or Meniere's specialist ENT, both groups do IT injections routinely).
 
Some people have tinnitus so minor they don't realise it's tinnitus. Some have had it so long they think the noise IS silence.

That said, for the majority, they DO know when they have tinnitus. I periodically checked and looked for noise - especially if I heard electrical static. It was NEVER tinnitus, and always a real noise.

Now I do have tinnitus.
Exactly this. Prior to having all-the-time/24-7 awareness of my tinnitus. I had a very faint "shhhhh" in my ear since about 2008 from someone firing a flare gun next to me. I didn't really consider it has the having the tinnitus that we all have today, but looking back, it definitely was the first sign of permanent damage. It just never bothered me because I would only hear it in specific circumstances, but not all the time.

There were times many, many years ago, when I had a home office in my basement where I would think that the desk lamp was making a noise. Now that I look back, it was probably the first sign of audible tinnitus.
 
What about the eardrum perforation after being injected with FX-322?

Does the the hole in the eardrum heal afterwards? Will it be as good as before the injection?
The eardrum does heal. The needle is incredibly small, so it sounds like it heals quickly. Some have mentioned that there may be a scar, but it does not seem to affect overall hearing.

Considering patients got 4 injections of FX-322 through the same eardrum, 1 per week, it seems like Frequency Therapeutics doesn't seem all that concerned with the effect of the injection need on the eardrum. Also, considering the injections are a week apart is a sign that most eardrums probably heal from the needle poke within that 7-day timespan.
 
The eardrum does heal. The needle is incredibly small, so it sounds like it heals quickly. Some have mentioned that there may be a scar, but it does not seem to affect overall hearing.

Considering patients got 4 injections of FX-322 through the same eardrum, 1 per week, it seems like Frequency Therapeutics doesn't seem all that concerned with the effect of the injection need on the eardrum. Also, considering the injections are a week apart is a sign that most eardrums probably heal from the needle poke within that 7-day timespan.
The eardrum heals in two days after the injection. I received 8 injections in the right ear (every third day of Dexamethasone injections) and after that I immediately had 10 treatments in the Hyperbaric Chamber and there was no problem :)

So the injection is not a problem.
 
@Diesel @Drachen

For myself I know I had no tinnitus that I was ever able to detect prior to this year. I can't really explain how or why, but I just know that I'd be in bed late at night and hear ny charger or my lights make noise. When unplugging these or plugging my ears while they were on... silence. Even while looking for a noise.

Unfortunately I had a whiplash, a 100 dB alarm go off next ti my ears, an earwax blockage and severe stress/anxiety all within the same two weeks and was left with horribly reactive tinnitus.

No measurable hearing loss though.
 
You can definitely have hearing loss without tinnitus.
Absolutely. Anyone interested in this particular topic should read the Dr. Will Sedley thread (Dr. Tzounopoulos has talked about this too). Tinnitus depends not just on the auditory interference but the presence of a "predictive brain" that tries to match expected input with actual input. Not everyone has a "predictive brain" and will need a lot more damage to produce tinnitus.
 
In most cases, the ear drum heals fine. One member had about 80 protein rich plasma injections in his ear drums over a few weeks without complications.

Ear drum perforations (this usually refers to a larger than expected defect after injection) are uncommon and usually heal except in rare cases.

An ENT who is used to giving IT injections will dramatically minimize this risk (otologist or Meniere's specialist ENT, both groups do IT injections routinely).
Protein rich plasma injections?

I recollect that this person underwent treatment entailing intratympanic injections of Platalet-rich plasma.

https://en.wikipedia.org/wiki/Platelet-rich_plasma
 
What about the eardrum perforation after being injected with FX-322?

Does the the hole in the eardrum heal afterwards? Will it be as good as before the injection?
I had intratympanic steroid injections after suffering sudden hearing loss. Yes, the hole heals after a while. It's weird if you cover your nose and blow you can feel air come out through the hole. Once I got the initial injection the hole stayed there for about a month or so until it healed.
 

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