Frequency Therapeutics — Hearing Loss Regeneration

Also if the drug is currently showing most benefit in the UHF regions, any differences may not be all that detectable by the person receiving the drug I'm guessing?
Interesting point. Maybe someone can help me on this question...

Frequency has mentioned a few times that they are filtering for a really homogeneous group of participants to join the trial; to show consistent improvement. We assume this group will look a lot like the Moderate-Moderately Severe group of the Phase 1/2.

Would someone with the tinnitus/hearing loss that comes with Moderate-Moderately Severe hearing loss in the standard PT range notice much of a "qualitative" difference after receiving FX-322?

Or, would the brain just adjust so slowly that it wouldn't seem like an improvement took place until it was measured by the current standards?
 
For me what I find interesting was the audiologist's response on the HLAA video, she deemed FX-322 to be very impressive, and the fact that she's almost rethinking her field was very interesting to me.
 
https://clinicaltrials.gov/ct2/show/NCT04120116

We need to also keep in mind that this trial is Quadruple Blinded.

Participant, Care Provider, Investigator, Outcomes Assessor

If my Googling is correct... that means that the participant should not only be blinded to whether or not they got placebo, but also how they did on the follow up tests. So, if they did get any number of shots of FX-322, they won't know if their word score increased, audiogram improved, etc from the care provider or investigator at the trial.

Of course, they could go off to an audiologist and get tested on their own.
 
Interesting point. Maybe someone can help me on this question...

Frequency has mentioned a few times that they are filtering for a really homogeneous group of participants to join the trial; to show consistent improvement. We assume this group will look a lot like the Moderate-Moderately Severe group of the Phase 1/2.

Would someone with the tinnitus/hearing loss that comes with Moderate-Moderately Severe hearing loss in the standard PT range notice much of a "qualitative" difference after receiving FX-322?

Or, would the brain just adjust so slowly that it wouldn't seem like an improvement took place until it was measured by the current standards?
Look at the phase 1 results:

Some results from the word recognition test:
14/50 to 34/50
20/50 to 39/50
26/50 to 47/50

Of course you notice that in your day to day life, it's an incredible improvement. Some people barely understood speech before but are now able to have a near normal conversation (if you recognize 80% of words often the context will be sufficient to fill in the gap).
 
How much a single ear treatment will improve bi-lateral tinnitus should be considered in the phase 2a study. There may not be stellar results until both ears are treated.
 
He should.
Potentially, by publicly posting, he could delay recruiting (which could delay the drug release), so low information anecdotes especially do a lot more harm than good.

50% of people get either placebo or phase 1 dosing.

If someone doesn't have a lot of problem related to UHF loss or has placebo, then they likely wouldn't notice anything at all in those two scenarios.

That's why I think if you are going to potentially affect recruitment with stuff like this, at least post before and after audiograms so we know what we are looking at. Otherwise, it's fearful speculation that may be completely irrelevant at best and something that could even delay release at worst with zero benefit in terms of meaningful speculation.

But honestly, they have NDAs for a reason and people should respect that. I know April seems forever away to wait for results but that's going to give us the answers.
 
If you only gain 10 dB at 8 kHz, you aren't going to feel any improvement.

Heck 10 dB at any frequency and you aren't going to feel or hear any improvement.

Same for tinnitus. I doubt any small improvement will get rid of it.

We are all just guessing, but I'm pretty sure you need to get back to perfect hearing once you have tinnitus for it to go away. People get tinnitus with as little as 10 dB loss. Once you have it, and you know you have it, I'm pretty sure you need to get back to baseline for it to go away. As for small improvements... It isn't a linear scale where you gain 10 dB of hearing and your tinnitus gets better by that much. There are so many factors that contribute to its loudness.

I'm not sure if his post is good or bad, but we really need to see improvements in the 30 to 50 dB range for FX-322 to help people, or whatever your hearing loss is...
 
If you only gain 10 dB at 8 kHz, you aren't going to feel any improvement.

Heck 10 dB at any frequency and you aren't going to feel or hear any improvement.

Same for tinnitus. I doubt any small improvement will get rid of it.

We are all just guessing, but I'm pretty sure you need to get back to perfect hearing once you have tinnitus for it to go away. People get tinnitus with as little as 10 dB loss. Once you have it, and you know you have it, I'm pretty sure you need to get back to baseline for it to go away. As for small improvements... It isn't a linear scale where you gain 10 dB of hearing and your tinnitus gets better by that much. There are so many factors that contribute to its loudness.

I'm not sure if his post is good or bad, but we really need to see improvements in the 30 to 50 dB range for FX-322 to help people, or whatever your hearing loss is...
What are you basing this off on?

Couple of thoughts:

1) 10 dB isn't small potatoes. Even if it doesn't change the tinnitus, the increase in hearing ambient noises will be a relief.
2) People have reported tinnitus abating with hearing aids and cochlear implants. I don't think these completely restoring hearing (though I could be wrong.) So I think we need to be a little more cautious on how we project a novel treatment is going to work.
 
I'm not sure if his post is good or bad, but we really need to see improvements in the 30 to 50 dB range for FX-322 to help people, or whatever your hearing loss is...
Hopefully we see that in the extended audiograms. Then it would just be a matter of drug delivery, but at least that would mean that the concept works.

Does anyone know how much dB of hearing cochlear implants would restore? I guess it could be a decent comparison about what to expect.
 
Hopefully we see that in the extended audiograms. Then it would just be a matter of drug delivery, but at least that would mean that the concept works.

Does anyone know how much dB of hearing cochlear implants would restore? I guess it could be a decent comparison about what to expect.
Eh Cochlear implants are not a good comparison. They don't restore natural hearing as much as bypass the hair cells entirely to send a (crude) electrical signal at spaced out intervals to the spiral ganglion neurons. They improve your audiogram tremendously because they allow you to hear sound even if that sound quality is relatively meh (but gets better as they add better and more electrodes and use better processing).
 
10 dB in hearing improvement = 4x the sensitivity to the human ear.

One would think that an improvement on an audiogram from a "worse" threshold at a baseline might be more noticeable if it's 10 dB.

For example, if one's baseline on the audiogram from 4 kHz-8 kHz was roughly 50 dB; and it improved to 40 dB... it might be more noticeable than if it went from 20 dB to 10 dB.

There is probably no research to prove this, only Frequency Therapeutics knows.
 
If you only gain 10 dB at 8 kHz, you aren't going to feel any improvement.

Heck 10 dB at any frequency and you aren't going to feel or hear any improvement.

Same for tinnitus. I doubt any small improvement will get rid of it.

We are all just guessing, but I'm pretty sure you need to get back to perfect hearing once you have tinnitus for it to go away. People get tinnitus with as little as 10 dB loss. Once you have it, and you know you have it, I'm pretty sure you need to get back to baseline for it to go away. As for small improvements... It isn't a linear scale where you gain 10 dB of hearing and your tinnitus gets better by that much. There are so many factors that contribute to its loudness.

I'm not sure if his post is good or bad, but we really need to see improvements in the 30 to 50 dB range for FX-322 to help people, or whatever your hearing loss is...
I'm going to dissect your post bit by bit and give my view on what you said.

We know people have tinnitus and no hearing loss and people have hearing loss and no tinnitus. What this tends to indicate is that tinnitus and hearing loss are actually not inherently linked.

Multiple participants in the phase 1 trial noted improvements in tinnitus. However, what we don't know definitively is whether their tinnitus improvement came from improvements in hearing thresholds or from another source such as synaptic recovery. This is due to insufficient testing. Therefore, we still do not have any clarity as to the reason participants had a reduction in tinnitus. Hence it is impossible to determine both what type of hearing improvement is needed and also what level of improvement is needed to improve or eliminate tinnitus.

CI and hearing aid users have had improvement in their tinnitus (and quite significantly too). The generally well established reason is the extra stimulation delivered, particularly to the high frequency range where the overwhelming majority of daily sounds sit.

However, what we do not know is how much extra stimulation is given to people when utilising a hearing aid. Apparently the amount of stimulation delivered at a particular frequency can often be insufficient to theoretically return someone to baseline level. Yet while using a hearing aid, the user has no symptoms of tinnitus. This suggests that it isn't actually necessary to return hearing thresholds to baseline to eliminate tinnitus.

While a 10 dB improvement as indicated in phase 1 results isn't significant, it is meaningful. Also the increase was only shown at a single frequency due to the testing criteria in the inaugural trial. It is very much possible that there was an improvement above 10 dB in the very high frequencies in the initial trial and this is plausible due to the word recognition score test results.

Therefore I very strongly believe that it is near impossible to determine how much hearing improvement is required and also where that improvement specifically needs to be had in order to eliminate tinnitus. Since we have evidence which suggests you can eliminate tinnitus without returning hearing thresholds to baseline, I would hypothesise that the required improvements you mentioned such as returning hearing levels to baseline levels are not actually required to eliminate tinnitus entirely.
 
What are you basing this off on?

Couple of thoughts:

1) 10 dB isn't small potatoes. Even if it doesn't change the tinnitus, the increase in hearing ambient noises will be a relief.
2) People have reported tinnitus abating with hearing aids and cochlear implants. I don't think these completely restoring hearing (though I could be wrong.) So I think we need to be a little more cautious on how we project a novel treatment is going to work.
1. 10 dB at 8 kHz is small potatoes... Sure it's a miracle that they were able to do anything at all and a breakthrough by itself. Most people though are down 20 dB, 30 dB, 40 dB, 50 dB, ... at lower frequencies, not just at 8 kHz where FX-322 might not have reached. The word scores improving mattered though. If the 10 dB at 8 kHz helped get better word scores then great but we are still speculating on that one. Extended audiograms could also provide more insight on that one. If people were gaining 40 dB at 10 kHz because FX-322 got there easier... that could be something to celebrate.

2. I was one that reported having hearing aids and I didn't get tinnitus until I was much older. I've worn them for approx 25 years. Hearing aids get you back to baseline if the hearing test is correct and the hearing aids are programmed correctly. That kept me from getting tinnitus. Once my hearing dropped to the point where the hearing aids were no longer able to get me to baseline, I got tinnitus. There were other factors as well. I'm older now, and have had some bad anxiety...
Without the hearing aids I have a rock concert going on in my head. They do help keep tinnitus down when I wear them, but they don't make it go away. Just like everyone, I have good days and bad days.

Don't get me wrong. You are correct that every little bit helps. If you are down 20 dB at 8 kHz and you get back 10 dB this is great news. That might be the difference between hearing well and saying "what" some of the time. Even in this case though I don't think it's enough to make tinnitus go away or something someone would notice. It might provide a little relief though. Again it's just my theory from a guy that likes to experiment on himself and dealt with hearing loss all his life...
 
Hopefully we see that in the extended audiograms. Then it would just be a matter of drug delivery, but at least that would mean that the concept works.

Does anyone know how much dB of hearing cochlear implants would restore? I guess it could be a decent comparison about what to expect.
Agreed. Extended audiograms would be extremely helpful. If he gained 30 dB at 10 kHz...This could mean FX-322 has more potential. Again it's not something you might notice but this could help people that have tinnitus in the higher frequency range. Drug delivery could help with the lower frequencies as well. Dosage might help as well. Multiple injections could help as well.

I'm looking into doing a CI. From what I've read you get back quite a few dB and maybe back to baseline. The issue is that it's not "natural" hearing. I'm guessing it might sound more computerized???? I do know people report being able to hear higher frequencies that they couldn't hear before.
 
So from what I've been reading, it sounds like FX-322 isn't likely to do anything for pain hyperacusis and noxacusis/reactive tinnitus since the underlying issue is not dead hair cells? Some people seem to believe that broken synapses are the issue. I'm more concerned about this than the tinnitus itself. If so, then are there any regenerative treatments/cures in the works to address those issues (hopefully in the near future)?
 
If you only gain 10 dB at 8 kHz, you aren't going to feel any improvement.

Heck 10 dB at any frequency and you aren't going to feel or hear any improvement.

Same for tinnitus. I doubt any small improvement will get rid of it.

We are all just guessing, but I'm pretty sure you need to get back to perfect hearing once you have tinnitus for it to go away. People get tinnitus with as little as 10 dB loss. Once you have it, and you know you have it, I'm pretty sure you need to get back to baseline for it to go away. As for small improvements... It isn't a linear scale where you gain 10 dB of hearing and your tinnitus gets better by that much. There are so many factors that contribute to its loudness.

I'm not sure if his post is good or bad, but we really need to see improvements in the 30 to 50 dB range for FX-322 to help people, or whatever your hearing loss is...
A 10 dB improvement is massive. In fact, the fact that FX-322 can regenerate hearing at all is massive.
I'm pretty sure I would notice a 10 dB improvement seems as I am down to -50 dB at 8000 Hz. Getting that to -40 dB would be hugely relieving... to know that deafness is likely further away.

It will be interesting to see if a 10 dB improvement has any effect on tinnitus, or as you say hearing needs to be perfect before it may disappear. Got to remember though that there may be other damage to the cochlear that may be playing a part in tinnitus and which FX-322 does not address.
 
What are you basing this off on?

Couple of thoughts:

1) 10 dB isn't small potatoes. Even if it doesn't change the tinnitus, the increase in hearing ambient noises will be a relief.
2) People have reported tinnitus abating with hearing aids and cochlear implants. I don't think these completely restoring hearing (though I could be wrong.) So I think we need to be a little more cautious on how we project a novel treatment is going to work.
10 dB is not small potatoes, but 10 dB in one frequency is really not that great loudness wise (I'm not talking about clarity). If you told people here back in 2017 this drug would add 10 dB in one frequency, there wouldn't nearly be the hype this drug got. If I look at how Frequency Therapeutics talks about this drug now, they themselves have probably lowered their expectations. That's not an indictment of Frequency Therapeutics, that's what drug testing is for. It also doesn't mean it couldn't be a big help to people. But the bottom line is we need better results in Phase 2a than we got in Phase 1/2.
 
If you only gain 10 dB at 8 kHz, you aren't going to feel any improvement.

Heck 10 dB at any frequency and you aren't going to feel or hear any improvement.

Same for tinnitus. I doubt any small improvement will get rid of it.
Not sure I agree with this. For 28 years I had tinnitus that I could only hear at night. I'm now able to hear it during the day as well and the difference between those two situations is considerable. If 10 dB means dialing down the tinnitus to a point where we get a decent enough break from it the quality of life benefit is going to be significant.
 
So from what I've been reading, it sounds like FX-322 isn't likely to do anything for pain hyperacusis and noxacusis/reactive tinnitus since the underlying issue is not dead hair cells? Some people seem to believe that broken synapses are the issue. I'm more concerned about this than the tinnitus itself. If so, then are there any regenerative treatments/cures in the works to address those issues (hopefully in the near future)?
Otonomy's OTO-413 is focused on synapse repair. It's yet to be proven it will do anything like FX-322 for hypercausis and tinnitus. I think the Hough pill goes on to target synapse repair. I think the synapses are damaged before hair cells are destroyed in noise trauma.
 
So from what I've been reading, it sounds like FX-322 isn't likely to do anything for pain hyperacusis and noxacusis/reactive tinnitus since the underlying issue is not dead hair cells? Some people seem to believe that broken synapses are the issue. I'm more concerned about this than the tinnitus itself. If so, then are there any regenerative treatments/cures in the works to address those issues (hopefully in the near future)?
Loudness hyperacusis is hypothesised to potentially be due to loss of type 1 synaptic fibers. However, noxacusis is thought to possibly be due to damage to the outer hair cells which consequently sensitises the type 2 afferent fibers - these fibers are resistant to damage and actually remain intact in damaged areas of the cochlea. So hair cell regeneration might help via restoration of OHCs - key word is 'might' though - as noxacusis remains relatively poorly understood although that is starting to change!
 
10 dB in hearing improvement = 4x the sensitivity to the human ear.

One would think that an improvement on an audiogram from a "worse" threshold at a baseline might be more noticeable if it's 10 dB.

For example, if one's baseline on the audiogram from 4 kHz-8 kHz was roughly 50 dB; and it improved to 40 dB... it might be more noticeable than if it went from 20 dB to 10 dB.

There is probably no research to prove this, only Frequency Therapeutics knows.
Exactly.

Amplitude ratio is:
10dB 3.162
20dB 10
30dB 31.62
40dB 100

https://en.wikipedia.org/wiki/Decibel
 
So from what I've been reading, it sounds like FX-322 isn't likely to do anything for pain hyperacusis and noxacusis/reactive tinnitus since the underlying issue is not dead hair cells? Some people seem to believe that broken synapses are the issue. I'm more concerned about this than the tinnitus itself. If so, then are there any regenerative treatments/cures in the works to address those issues (hopefully in the near future)?
Aren't Hough Ear Institute working with synapses?
 
I agree with @FGG, this person was irresponsible and put their own frustrations over the importance of this study.

The best way to think about the patients in the study is as puzzle pieces. Some will not improve, some will improve a bit, and some will improve tremendously. These pieces will all come together to create a clearer picture of how FX-322 will move forward, what its impact is, and who the most suitable patients are. But separately they are just pieces of a puzzle, and you can't tell what the end picture will be from one tiny fragment.
 
Below is an 8000 Hz pure tone which changes upward 10 dB. It's significant. Be sure to turn your system volume down before playing.
 

Attachments

  • 8k tone 10db diff.mp3
    97.3 KB · Views: 105

Log in or register to get the full forum benefits!

Register

Register on Tinnitus Talk for free!

Register Now