Frequency Therapeutics — Hearing Loss Regeneration

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.
If this is true, I applaud them waiting to fill the trial. Looking forward to some breakthrough data in Q2/2021.
 
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.
I don't think it's going to be delayed. The testing is done up to 210 days or 7 months, which would bring us to March for the last of the enrolled participants. That gives them a month to analyze and aggregate all the data, so we can probably expect results in April.
 
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?
Nothing to see here... move along folks... move along. He still owns a huge chunk, those disposals are a small fraction of his ownership.
 
@FGG,

Do you perhaps know how aminoglycosides damage the cochlea? Is it neuronal or hair cell damage, or both? Have there been proposed theories on the ototoxicity mechanism of action for this type of antibiotic? It's been kind of hard searching it. I was wondering if FX-322 will help in this case. Thank you.
 
I don't think it's going to be delayed. The testing is done up to 210 days or 7 months, which would bring us to March for the last of the enrolled participants. That gives them a month to analyze and aggregate all the data, so we can probably expect results in April.
I hope you're right, but I'm not betting on it. They finished enrollment for Phase 1/2 in October 2019 and came out with results in April 2020. They followed patients for 3 months in that trial. Their Phase 2a trial has 4 times as many patients, 4 injections instead of 1 and they are following them 4 months longer. I'm counting on June 2021, possibly with even more delay.
 
@FGG,

Do you perhaps know how aminoglycosides damage the cochlea? Is it neuronal or hair cell damage, or both? Have there been proposed theories on the ototoxicity mechanism of action for this type of antibiotic? It's been kind of hard searching it. I was wondering if FX-322 will help in this case. Thank you.
It's primarily hair cell (causes apoptosis of hair cells).

PubMed is a good place to look it up if you need more details.
 
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.
This is my first time buying stock and I'm finding it to be good therapy. It's fun and it gives me hope. I'd rather take my chances on this than go to my local casino. My guess is we have at least a 50% shot at making some money and getting some of our hearing restored. Frequency Therapeutics has a good team, they're in the lead and I'm happy to be part of it in a small way.
 
I hope you're right, but I'm not betting on it. They finished enrollment for Phase 1/2 in October 2019 and came out with results in April 2020. They followed patients for 3 months in that trial. Their Phase 2a trial has 4 times as many patients, 4 injections instead of 1 and they are following them 4 months longer. I'm counting on June 2021, possibly with even more delay.
It's common for the sponsor to release top line / summary results shortly after announcing the end of the trial. I would expect them to share a summary metric for each cohort across each primary and secondary endpoint.

Ex: Word score improved x% in the 2-dose group.
 
Ah. Nevermind, I forgot that FX's animal studies used gentamicin (aminoglycosides) to induce hair cell death for their in situ cochlear explant studies. So FX-322 should still work with aminoglycosides antibiotics.
 
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.
Specifically in reference to this: 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?

Some people do, in fact, experience less tinnitus, sometimes much less, after getting hearing aids. In fact several months ago a Tinnitus Talk member did, and I'm not going to jinx her by looking her up. I've had hearing loss and tinnitus for what, over a year and a half now, and I am pretty sure I experienced some reduction in my baseline tinnitus after I got my aids.

But this experience is unpredictable, partly I'm sure because as another posted said hearing aids do not restore your hearing system back to being a 20-year-old. And all of us know how unpredictable tinnitus can be--I had a bizarre experience starting last weekend where for no obvious reason my tinnitus went nutso and I'm certain my hearing declined in my bad ear--but when I finally got to the hearing center three days later, I was feeling better and my hearing test showed results virtually exactly the same as last November!

Anyway long story short hearing aids can help reduce tinnitus although it's by no means guaranteed. And I think the science is sold that restoring natural hearing through FX-322 has better odds.
 
It's common for the sponsor to release top line / summary results shortly after announcing the end of the trial. I would expect them to share a summary metric for each cohort across each primary and secondary endpoint.

Ex: Word score improved x% in the 2-dose group.
Hope you're right. It didn't happen with Phase 1/2.
 
I see people speculating if FX-322 will help hyperacusis/noxacusis. Any speculation on if regeneration via FX-322 or another drug will help with TTTS at all?

Also, my tinnitus is very reactive. When people speak of improvement, I wonder about reactivity.

Of course it's great to see these drugs in development and ideally coming out in the next few years for many that are suffering from tinnitus that is debilitating in its own right. I can't lie and say I'm not worried that nothing will help with major parts of my own personal issues which come from TTTS, hyperacusis, intermittent noxacusis, and major reactivity.
 
I see people speculating if FX-322 will help hyperacusis/noxacusis. Any speculation on if regeneration via FX-322 or another drug will help with TTTS at all?

Also, my tinnitus is very reactive. When people speak of improvement, I wonder about reactivity.

Of course it's great to see these drugs in development and ideally coming out in the next few years for many that are suffering from tinnitus that is debilitating in its own right. I can't lie and say I'm not worried that nothing will help with major parts of my own personal issues which come from TTTS, hyperacusis, intermittent noxacusis, and major reactivity.
I don't think it will help with TTTS as that is caused by the tensor tympani muscle spasm or some disorder. The tensor tympani muscle has nothing to do with the inner ear or cochlear hair cells and since FX-322 is addressing hearing issues at the inner ear, TTTS is unlikely to be affected, unfortunately.
 
I don't think it will help with TTTS as that is caused by the tensor tympani muscle spasm or some disorder. The tensor tympani muscle has nothing to do with the inner ear or cochlear hair cells and since FX-322 is addressing hearing issues at the inner ear, TTTS is unlikely to be affected, unfortunately.
I could see it potentially having a positive impact on TTTS if middle ear hyperactivity arises as a consequence of inner ear damage. It seems that for many people problems with TTTS are usually triggered initially by some sort of acoustic trauma/noise over-exposure.
 
Just wondered if anyone else has read this acoustic shock model paper? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

@grate_biff posted it several months ago (thanks) and I've read it a few times now. Each time I read it, I understand it and research the content a bit better and I'm starting to think that the mechanics behind acoustic shock induced noxacusis pain, including repeat injury (setbacks), TTTS, and possibly acoustic shock induced tinnitus are staring us in the face in this paper. I'm leaning more and more to a middle ear problem as a primary cause for acoustic shock induced noxacusis re-injury, pain and setbacks. And also whatever nerve blocker this paper talks about as the primary possible treatment (it doesn't actually say what it is though, maybe stellate ganglion block?). It seems the tensor tympani muscle can get very badly damaged during an acoustic shock and produce a lot of inflammation and nerve sensitization in the facial area, and most importantly become primed for constant re-injury.

The main thing I'm still trying to work out with regard to the referred pain this paper talks about (i.e. the delayed facial, jaw, neck pain), is the way the nerve pathways work between the middle ear and the cochlea. It's well noted that during acoustic shock ATP can possibly diffuse from the middle ear through the round window to the cochlea, but I can't find a direct nerve link between the middle ear and the cochlea for the cochlea to send pain signals back the other way (although this paper says that there is one, anyone know?). It seems that the only nerve links between the inner ear and the cochlea are via higher up parts of the nerve system. (trigeminocervical complex and cochlear nucleus). I think it's less likely anyway that the pain signal is being produced by the cochlea for acoustic shock noxacusis. I think it's more likely that the previously damaged tensor tympani muscle is being re-injured either because its having trouble healing (due to a noisy environment and hence why it's impossible to 'push through the pain barrier' with noxacusis) or because of some kind of lowered nervous system threshold that's making it so unnecessarily active that it cannot rest and heal even in relative quiet. According to this paper the tensor tympani muscle injury can cause sensitization that occurs in the trigeminal nerve mandibular branch which makes sense because that branch seems to connect to every crucial area or muscle where either noxacusis referred pain is associated, or areas that are related to the acoustic trauma injury. In particular the tensor tympani muscle itself, the middle ear mucosa, the outer ear drum, and these muscles; masseter, temporalis, lateral and medial pterygoid, the tensor veli palatini, the mylohyoid muscle, and anterior belly of the digastric muscle. (Basically the muscles just under/in front of the ear, cheek and jaw). The way I read it is that every time the vulnerable tensor tympani muscle get over exposed to noise it causes middle ear inflammation and triggers pain throughout the mandibular nerve and those muscles. I seriously cannot see how my cochlea can be receiving enough noise exposure to even be vunerable to any noise damage these days anyway even though I still get setbacks.
 
Just wondered if anyone else has read this acoustic shock model paper? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

@grate_biff posted it several months ago (thanks) and I've read it a few times now. Each time I read it, I understand it and research the content a bit better and I'm starting to think that the mechanics behind acoustic shock induced noxacusis pain, including repeat injury (setbacks), TTTS, and possibly acoustic shock induced tinnitus are staring us in the face in this paper. I'm leaning more and more to a middle ear problem as a primary cause for acoustic shock induced noxacusis re-injury, pain and setbacks. And also whatever nerve blocker this paper talks about as the primary possible treatment (it doesn't actually say what it is though, maybe stellate ganglion block?). It seems the tensor tympani muscle can get very badly damaged during an acoustic shock and produce a lot of inflammation and nerve sensitization in the facial area, and most importantly become primed for constant re-injury.

The main thing I'm still trying to work out with regard to the referred pain this paper talks about (i.e. the delayed facial, jaw, neck pain), is the way the nerve pathways work between the middle ear and the cochlea. It's well noted that during acoustic shock ATP can possibly diffuse from the middle ear through the round window to the cochlea, but I can't find a direct nerve link between the middle ear and the cochlea for the cochlea to send pain signals back the other way (although this paper says that there is one, anyone know?). It seems that the only nerve links between the inner ear and the cochlea are via higher up parts of the nerve system. (trigeminocervical complex and cochlear nucleus). I think it's less likely anyway that the pain signal is being produced by the cochlea for acoustic shock noxacusis. I think it's more likely that the previously damaged tensor tympani muscle is being re-injured either because its having trouble healing (due to a noisy environment and hence why it's impossible to 'push through the pain barrier' with noxacusis) or because of some kind of lowered nervous system threshold that's making it so unnecessarily active that it cannot rest and heal even in relative quiet. According to this paper the tensor tympani muscle injury can cause sensitization that occurs in the trigeminal nerve mandibular branch which makes sense because that branch seems to connect to every crucial area or muscle where either noxacusis pain is associated, or areas that are related to the acoustic trauma injury. In particular the tensor tympani muscle itself, the middle ear mucosa, the outer ear drum, and these muscles; masseter, temporalis, lateral and medial pterygoid, the tensor veli palatini, the mylohyoid muscle, and anterior belly of the digastric muscle. (Basically the muscles just under/in front of the ear, cheek and jaw). The way I read it is that every time the vulnerable tensor tympani muscle get over exposed to noise it causes middle ear inflammation and triggers pain throughout the mandibular nerve and those muscles. I seriously cannot see how my cochlea can be receiving enough noise exposure to even be venerable to any noise damage these days anyway.

This is really interesting, a lot of food for thought. One thing I'm wondering is how do you determine whether you've suffered an acoustic shock versus regular acoustic trauma? How do we determine whether someone is suffering from acoustic-shock induced noxacusis vs acoustic trauma noxacusis since they might be separate pathologies? I've seen that paper before although I'll need to reread it as there's a lot to digest!
 
@100Hz interesting. Again I wonder how this translates to people who suffered an acoustic shock but do not have noxacusis at all. I also wonder if this may be, in part, reason for fluctuating and reactive tinnitus... man, all of this is horrible and I really wish they were able to understand the workings of the ear better.
 
This is really interesting, a lot of food for thought. One thing I'm wondering is how do you determine whether you've suffered an acoustic shock versus regular acoustic trauma? How do we determine whether someone is suffering from acoustic-shock induced noxacusis vs acoustic trauma noxacusis since they might be separate pathologies? I've seen that paper before although I'll need to reread it as there's a lot to digest!
Not sure but it's a good question. I think they're separate pathologies although there's potentially a one way link between them as well (acoustic shock can apparently cause inner ear noxacusis).

The trouble with this is that obviously some people will know they've had one for sure, whereas some people won't be so sure. And others will know they haven't had one. I'm hoping that the subtle differences in symptoms will be a good start (for example would non acoustic shock sufferers get the delayed facial pain?). And the paper above indicates that acoustic shocks can be quite low level in that you'd recover fully from any acute symptoms. But that's not to say that you might not have now primed your tympanic muscle for further injury.

Also you have any degree or severity of combination of the 2, in either ear to think about as well.

Also maybe it just doesn't matter because it looks like FX-322 would potentially cure one of them and whatever that nerve blocker is (wish I could find out) would treat the other one.
 
@100Hz interesting. Again I wonder how this translates to people who suffered an acoustic shock but do not have noxacusis at all. I also wonder if this may be, in part, reason for fluctuating and reactive tinnitus... man, all of this is horrible and I really wish they were able to understand the workings of the ear better.
If you read that paper there's a good section on tinnitus and some kind of vicious cycle that it apparently gets into with the middle ear inflammation that I would imagine that nerve blocker would help as well.
 
Not sure but it's a good question. I think they're separate pathologies although there's potentially a one way link between them as well (acoustic shock can apparently cause inner ear noxacusis).

The trouble with this is that obviously some people will know they've had one for sure, whereas some people won't be so sure. And others will know they haven't had one. I'm hoping that the subtle differences in symptoms will be a good start (for example would non acoustic shock sufferers get the delayed facial pain?). And the paper above indicates that acoustic shocks can be quite low level in that you'd recover fully from any acute symptoms. But that's not to say that you might not have now primed your tympanic muscle for further injury.

Also you have any degree or severity of combination of the 2, in either ear to think about as well.

Also maybe it just doesn't matter because it looks like FX-322 would potentially cure one of them and whatever that nerve blocker is (wish I could find out) would treat the other one.
This is a really good question - it seems that the defining characteristic of acoustic shock is that it is a sudden, unexpected sound that can take you by surprise. I've never experienced an acoustic shock but from my own experience of regular acoustic trauma, I also had the delayed facial/trigeminal pain. So I think it could be tricky to distinguish the symptoms. I did experience some thumping in my middle ear muscles (the tensor tympani) e.g. when I shut one eye but the classic middle-ear thumping/TTTS spasms was not really an issue for me. So perhaps acoustic shock sufferers display more middle-ear symptoms?
 
If you read that paper there's a good section on tinnitus and some kind of vicious cycle that it apparently gets into with the middle ear inflammation that I would imagine that nerve blocker would help as well.
I just read through it some. It actually paints a clear picture, but man, does it suck. I really want to know what nerve blocker this is, though, and I hope that some people will look into it more. The fact that there may be treatments available for some of us that no doctor knows about is so, so sad and painful.

It does make me wonder about a few things - but the overstimulation of the brain may also explain the onset or worsening of visual snow/visual snow syndrome for some. It may also explain why some people benefit from sleeping in silent environments and experience a quieter volume in the morning. Maybe these things are mentioned in the paper, sorry if they are - I skimmed through it as I don't have the energy or attention span to read the entire paper these days.

I still don't understand what exactly it is that makes some people experience noxacusis, and some none at all, even if the same process is responsible for symptoms.
 
Just wondered if anyone else has read this acoustic shock model paper? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

@grate_biff posted it several months ago (thanks) and I've read it a few times now. Each time I read it, I understand it and research the content a bit better and I'm starting to think that the mechanics behind acoustic shock induced noxacusis pain, including repeat injury (setbacks), TTTS, and possibly acoustic shock induced tinnitus are staring us in the face in this paper. I'm leaning more and more to a middle ear problem as a primary cause for acoustic shock induced noxacusis re-injury, pain and setbacks. And also whatever nerve blocker this paper talks about as the primary possible treatment (it doesn't actually say what it is though, maybe stellate ganglion block?). It seems the tensor tympani muscle can get very badly damaged during an acoustic shock and produce a lot of inflammation and nerve sensitization in the facial area, and most importantly become primed for constant re-injury.

The main thing I'm still trying to work out with regard to the referred pain this paper talks about (i.e. the delayed facial, jaw, neck pain), is the way the nerve pathways work between the middle ear and the cochlea. It's well noted that during acoustic shock ATP can possibly diffuse from the middle ear through the round window to the cochlea, but I can't find a direct nerve link between the middle ear and the cochlea for the cochlea to send pain signals back the other way (although this paper says that there is one, anyone know?). It seems that the only nerve links between the inner ear and the cochlea are via higher up parts of the nerve system. (trigeminocervical complex and cochlear nucleus). I think it's less likely anyway that the pain signal is being produced by the cochlea for acoustic shock noxacusis. I think it's more likely that the previously damaged tensor tympani muscle is being re-injured either because its having trouble healing (due to a noisy environment and hence why it's impossible to 'push through the pain barrier' with noxacusis) or because of some kind of lowered nervous system threshold that's making it so unnecessarily active that it cannot rest and heal even in relative quiet. According to this paper the tensor tympani muscle injury can cause sensitization that occurs in the trigeminal nerve mandibular branch which makes sense because that branch seems to connect to every crucial area or muscle where either noxacusis referred pain is associated, or areas that are related to the acoustic trauma injury. In particular the tensor tympani muscle itself, the middle ear mucosa, the outer ear drum, and these muscles; masseter, temporalis, lateral and medial pterygoid, the tensor veli palatini, the mylohyoid muscle, and anterior belly of the digastric muscle. (Basically the muscles just under/in front of the ear, cheek and jaw). The way I read it is that every time the vulnerable tensor tympani muscle get over exposed to noise it causes middle ear inflammation and triggers pain throughout the mandibular nerve and those muscles. I seriously cannot see how my cochlea can be receiving enough noise exposure to even be vunerable to any noise damage these days anyway even though I still get setbacks.
Can a middle ear muscle be injured just by sound, really? I mean you can damage your hair cells / synapses by sound. May be sound levels that rupture the ear drum can cause middle ear muscle injury. But I was never exposed to such sound levels, yet my middle ear muscle feels injured and is acting weird. I am more of the opinion this is due to inner ear injury.
 
Just wondered if anyone else has read this acoustic shock model paper? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156190/

@grate_biff posted it several months ago (thanks) and I've read it a few times now. Each time I read it, I understand it and research the content a bit better and I'm starting to think that the mechanics behind acoustic shock induced noxacusis pain, including repeat injury (setbacks), TTTS, and possibly acoustic shock induced tinnitus are staring us in the face in this paper. I'm leaning more and more to a middle ear problem as a primary cause for acoustic shock induced noxacusis re-injury, pain and setbacks. And also whatever nerve blocker this paper talks about as the primary possible treatment (it doesn't actually say what it is though, maybe stellate ganglion block?). It seems the tensor tympani muscle can get very badly damaged during an acoustic shock and produce a lot of inflammation and nerve sensitization in the facial area, and most importantly become primed for constant re-injury.

The main thing I'm still trying to work out with regard to the referred pain this paper talks about (i.e. the delayed facial, jaw, neck pain), is the way the nerve pathways work between the middle ear and the cochlea. It's well noted that during acoustic shock ATP can possibly diffuse from the middle ear through the round window to the cochlea, but I can't find a direct nerve link between the middle ear and the cochlea for the cochlea to send pain signals back the other way (although this paper says that there is one, anyone know?). It seems that the only nerve links between the inner ear and the cochlea are via higher up parts of the nerve system. (trigeminocervical complex and cochlear nucleus). I think it's less likely anyway that the pain signal is being produced by the cochlea for acoustic shock noxacusis. I think it's more likely that the previously damaged tensor tympani muscle is being re-injured either because its having trouble healing (due to a noisy environment and hence why it's impossible to 'push through the pain barrier' with noxacusis) or because of some kind of lowered nervous system threshold that's making it so unnecessarily active that it cannot rest and heal even in relative quiet. According to this paper the tensor tympani muscle injury can cause sensitization that occurs in the trigeminal nerve mandibular branch which makes sense because that branch seems to connect to every crucial area or muscle where either noxacusis referred pain is associated, or areas that are related to the acoustic trauma injury. In particular the tensor tympani muscle itself, the middle ear mucosa, the outer ear drum, and these muscles; masseter, temporalis, lateral and medial pterygoid, the tensor veli palatini, the mylohyoid muscle, and anterior belly of the digastric muscle. (Basically the muscles just under/in front of the ear, cheek and jaw). The way I read it is that every time the vulnerable tensor tympani muscle get over exposed to noise it causes middle ear inflammation and triggers pain throughout the mandibular nerve and those muscles. I seriously cannot see how my cochlea can be receiving enough noise exposure to even be vunerable to any noise damage these days anyway even though I still get setbacks.
Your description along with my crude understanding of this research page eerily describes the initial, very serious symptoms I had experienced from an outing shortly after my original acoustic trauma (I didn't realize at the time the severity of my injury.) Even now, typing this I am reminded of smaller setbacks that I have had where the pain and irritation of the middle ear had a delayed effect.
 
I see people speculating if FX-322 will help hyperacusis/noxacusis. Any speculation on if regeneration via FX-322 or another drug will help with TTTS at all?.
How long have you suffered from TTTS? It may still go away, months after your original trauma.

I suffered from it for about 6-8 months after my acoustic trauma. Then it went away. It either healed... or I got less anxious around medium-loudness situations. It seemed to go away around the same time my mild hyperacusis lessened.

Now I'm no expert... I may just have been lucky enough for my nerves to heal sufficiently so that they tolerated just enough noise... not triggering TTTS anymore.

However, to me it felt like there was a fear-based trigger to TTTS. The first few months I was involuntarily scared to death of all sounds. Even harmless medium-volume ones. I suffered from TTTS constantly.

At that time I had no idea what TTTS was. I only read about it 4 months after my trauma, around the same time I was in therapy to cope with my anxiety caused by tinnitus through Acceptance & commitment therapy (a more meditation / eastern philosophy based cognitive behavior therapy).

I can't speak for everyone of course, but I always felt that once I knew that TTTS had a fear-based trigger and once I learned the techniques of calming my nerves and not have a panic attack after most sounds... TTTS really went away for me.

Now it only comes back after experiencing a loud sound (not medium ones) and after I start worrying about that sound. I also feel it if I am very stressed or agitated (at work etc). But after about two weeks it goes away again.

I know I digress from FX-322, but I just wanted to tell you that TTTS can still improve / heal up to months after your trauma. And understanding that it may have a fear-based trigger and that it is in itself harmless, may help you as well. Especially if you combine it with relaxation, meditation, yoga or act (CBT) exercises.

It is my guess that route may have more chance of success than FX-322 actually "curing" it.

Of course I can only speak from my personal experience. And as @Diesel says, there's definitely a healing component to it as well. Exposing yourself to noise too soon after your original trauma will make you suffer from TTTS for sure. I made that mistake too.

Good luck!

P.S: TTTS and my mild hyperacusis were a greater nuisance to me than tinnitus in itself. I hope it goes away for you at some point.
 

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