Frequency Therapeutics — Hearing Loss Regeneration

This is a good point. Unless the first dose is supposed to be a primer of sorts, which I think was rejected by those in this thread as a possibility early on, then you will obviously receive benefits to the higher frequencies as they will be restored first. Following that, if your symptom results from those higher frequencies being damaged, then there should be improvement.

 

I was thinking just now, what’s to stop them from recruiting people that only have tinnitus? LeBel mentioned that they had an internal acceptance “filter” that was kept secret. If not, they’d have participants with no tinnitus and not taking the TFI at all.

 

This is very thought provoking indeed, for instance, if both my left and right ears only hear up to about 13 kHz and the higher frequencies are targeted first by FX-322, then if they injected my left ear with the 4 kHz & 6 kHz loss, it would probably take multiple rounds.

So my thoughts are if my left ear is treated and the upper frequencies are restored and finally the 4 kHz & 6 kHz are restored, wouldn't I now be able to hear better in the higher frequencies in my left ear than the right ear? Thus creating another possibility for tinnitus to develop? Or have I missed/overthought this? Lol.

 

Heck, why not recruit all unilateral, high frequency tinnitus subjects to stack the deck.

 

I would say this is the current expectation, yeah. It's a darn shame that one shot can't get all the gel to fill up the cochlea, but evolution seemed to think it was a good idea to lock that puppy away in your head.

I don't see any possibility for tinnitus to result from restoring frequencies. I think I get what you mean: there will be a disparity in your ears as your left can now hear better than your right.

I don't know this with certainty, and I don't even know if it is understood for uncertain, but I will assume that tinnitus develops independent of both ears. Tinnitus resulting in hearing loss from your right ear will be because that right ear is deficient and not because your left ear is superior. This is my perspective as a layman, but I also have not yet read anything that indicates otherwise.

Honestly, the moral of the story is to get both of your ears treated if you have bilateral tinnitus from sensorineural hearing loss.

 

If tinnitus was what they were seeking approval for, this is what they would likely have done.

 

Getting a single shot with enough FX-322 to penetrate deeper into the cochlea may be a matter of reformulating their delivery gel. Not really a difficult problem to solve, just won’t be ready for the Phase 1 product. I’m sure this is in the pipeline at Frequency Therapeutics.

If the tinnitus is a symptom of SNHL, in my own experience and others that have discussed it here, it can develop significantly differently in either ear. This would explain people who have one-sided tinnitus following an acoustic trauma that occurred either to their left or right (firecracker, gun shot, etc).

Based on what we’ve seen from the Phase 1/2, I suspect that the damaged cells restored by FX-322 in the cochlea are “like-new” in terms of performance and durability; but those worn cells that aren’t touched by the drug will retain the aged state and eventually be fully worn out sooner than the treated ones. There also may be cases where there are areas where a mixture of “new” cells and “worn original” cells exist that may wear a little more quickly, and redosing is needed to regenerate those more worn cells a few years later.

I expect that over the long term, patients will need to return for re-dosing as those original, worn and untreated cells die off and need regenerated.

This is why this drug shouldn’t be seen as a cure for hearing loss or tinnitus. In reality, it’s like a “reset button” for hearing cells.

It’s highly likely that someone will get treated with the drug, their hearing and tinnitus will improve in the damaged frequencies, and then something like an airbag will cause newer damage to worn cells lower in the cochlea, causing new hearing loss and tinnitus.

 

Hello. I was poisoned by organophosphates which made me develop multiple chemical sensitivity.

I also became sensitive to medications.

Unfortunately, I was on ototoxic medications and developed ototoxicity which I'm sure I was more prone to because of my chemical sensitivity.

So now I think to myself, what about the cochlear vestibular nerve damage caused by ototoxicity? Can FX-322 help that? What's in FX-322? Can it itself be ototoxic?

I have to ask these questions because I can't play around anymore with medications. I have rare reactions almost any time. I'm really hopeful for this but for a special case like me... I always must be careful, I seem to be sensitive to things that aren't even deemed as unsafe...

 

I tried to find this answer but couldn't. Apologies if it's a bit silly.

Do you think having TTTS would affect receiving FX-322 injections?

 

As far as I'm concerned, this is beyond satisfactory. It is better than the total of zero treatments currently available for both of those, and it can certainly serve as an intermediary until something more akin to an all-out cure arrives.

 

I can't think of a single reason why that would be the case.

 

FX-322 only regrows hair cells (which, depending on your ototoxicity may be an issue for you also). Generally, when they refer to "neuropathy" though it's almost always the synapse part of the nerve that is damaged and there are synaptopathy drugs in clinical trial (OTO-413).

True cochleovestibular nerve damage seems very rare from my reading and is due to demyelinating conditions like GBS and MS. Organophosphates is the rare toxin however that may cause demyelination in very rare cases. Just because you were exposed does not mean that's your specific auditory injury though (how did you diagnose that?).

If that's your situation, though, Rinri Therapeutics is the drug company that might be able to help you with that aspect. Frequency Therapeutics also has a remyelination drug in pre-clinical but I'm not sure if that is more universal or just for MS.

Anyway, keep an eye on Rinri Therapeutics. They are researching repair of the nerve itself (among other things):

https://rinri-therapeutics.com/science/

P.S. None of Frequency Therapeutics' pre-clinical testing indicated the drug was ototoxic and they applied it directly to cell cultures. Their Phase 1 showed no issue in vivo either.

 

The slideshow from the recent panel presentation has been made available:

https://investors.frequencytx.com/static-files/16a21001-6397-409d-b760-77ef91e9658c

 

I check this thread from time to time.

I think too many people are too speculative about the (hopefully positive) effect of FX-322 on tinnitus and too hopeful about early market entrance.

My tinnitus has been intensive for the past 9 months - only the shower masks it (!)

I am at the edge between going crazy and somehow coping with it. I can't hear anything over 8 kHz in my left ear and 12 kHz in my right ear anymore. My tinnitus is very high pitched and consists of different tones.

Maybe FX-322 could help.

My subjective relief:

The best thing my psychotherapist said to me, as I am struggling with acceptance, is that I should look at my biography and name the things I first could not accept but found peace with or solutions for.

For me, I found about a dozen things, I guess you all could too.

Then I should explain how I could find acceptance or solutions or help coming off from the outside.

So he advised me to trust in me and to trust in time. That tinnitus will be the next thing I find peace with, acceptance or even healing, but I would not know how long the period of time waiting for it will be, but that I will achieve it at some point.

This is what I trust and it helps me a lot.

 

Wouldn't it be YES if the results are only fair and not good? If the results aren't great, they may hit the brakes, you never know...

 

He was only asking if moving a video off of YouTube spelled doom for the trial.

 

I think this question may have come up before and I apologise if I'm going over something that's already been discussed, but what does the hive mind make of page/slide 62 of 68, which shows the word-in-noise scores slightly declining over a period of 18 months or so, albeit not back to baseline. I remember seeing this before.

I can only see one of four possible explanations for this.

a) These newly generated hair cells are not as durable as the ones we're born with. Is this possible, or is there evidence that would suggest this is possible?

b) Hair cells that were not replaced/regenerated by FX-322 but were damaged have died off since the initial treatment - but I thought FX-322 treats damaged hair cells?

c) Test variance in scores. I think this is highly unlikely given that the variance in all cases is negative - typically several standard deviations - and in one case worse than the original baseline pre-treatment.

d) All patients experienced a false sense of security, causing more damage to their ears following treatment by exposing themselves to loud sounds again.

I find options (c) and (d) somewhat implausible, but maybe I'm wrong, or there's something else I haven't thought of here. Thoughts?

 

Well, I have to rule out Meniere's, and other things, including blood flow issues as I feel twitches and heartbeat in my right ear.

But before taking ototoxic drugs for the second time last year, I just had tinnitus which I had habituated to and hyperacusis. Now I have those in addition to mild low frequency hearing loss in my right ear. Tinnitus has also gone to unbearable level in that ear but is somewhat OK in the left ear.

Literally before taking the ototoxic drugs I did not have this.

Once I rule out things, I suspect FX-322 will help me but it won't be all I need. I have other neurological issues so I do suspect I'm in it for the long run.

 

I only have high frequency hearing loss.

 

Even if the Phase 2A only reproduces the Phase 1/2 results in all of the 3 cohorts (so, for some reason dosing doesn't work as expected), FX-322 is still a breakthrough and will still go to market.

 

Even from the simple experience of using single earplugs, it's clear that my ears will adjust very quickly to any imbalance between the two. Like, in a matter of minutes.

 

It's weird because in that same time frame the audiogram improved a bit more as I recall which can't be explained by A or B.

C seems unlikely.

I guess D is possible when you have a small sample size.

I thought of another possibility too, E:

Part of the word score improvement is due to some unknown effect (anti inflammatory, etc), that wears off over time and then you are left with baseline effects.

There are also additional possibilities I thought of.

1) I remembered how Otonomy excluded people with musical training from their study. My guess is because their brains know how to listen better and decode sounds with any given set of synapses. The same could be true here. People who no longer have to listen as hard probably get less attentive brains after 18 months (versus still having more attentive brains while also having the benefit of repair at 6 months).

2) It's possible the new IHCs lose a few of the initial synapses at 3 months without the support of things like BDNF. After all, the audiograms did not decline. This would point to a good synergy with synapse drugs, if so.

The bigger trials should shed a lot more light on this. If Frequency Therapeutics does another Tinnitus Talk Podcast, I want to ask them about this.

 

My thought is that the word scores continued to decline because the hair cells at/below 8 kHz continued to accumulate wear, and now they have deficiencies deeper in the cochlea.

 

I came across a comment elsewhere from someone reporting that they were given hearing aids for their hyperacusis as they suspect their hyperacusis is the result of hearing loss at certain frequencies. They reported that filling in those frequencies helped alleviate some of their hyperacusis - e.g. bars and concerts are still a no-go but they can now deal with traffic and overhead music.

It's not specified whether it was primarily loudness or pain and even though it's anecdotal it's encouraging at least because it's yet more evidence to suggest that restoring input should help, even if that input is fairly crude and rudimentary.

 

I would like to see the documentation for this please. Because this is news to me.

 

The context was that it doesn't repair demyelination of the auditory nerve. All of their corporate presentations on their website describe their method (look under "Investors and Media").

If your point was that the regenerated IHCs re-synapse with the SGNs, that does happen, too, but that wasn't the context of my reply.

 

Another study with no surprises linking hearing loss and tinnitus/hyperacusis.

Review: Neural Mechanisms of Tinnitus and Hyperacusis in Acute Drug-Induced Ototoxicity

 

These hyperacusis and tinnitus theories are making me believe again that FX-322 will work.

 

To try and inspire a bit of hopeful thinking, just consider now that there are a group of people out there right now in the process of having their hearing restored by FX-322. Words are becoming clearer. Sounds are sharper. Life is better.

They are the among the first in our species to conquer this insidious biological limitation. They will not be the only ones. This is the decade.

 

Salicylates seem especially activating on the NMDA receptor so that's not too surprising:

Salicylate Induces Tinnitus through Activation of Cochlear NMDA Receptors