Frequency Therapeutics — Hearing Loss Regeneration

[Lucifer]

I can't wait until these treatments become real where it restores our hearing and gets rid of both hyperacusis and tinnitus.

We know more than the audiologists and ENT specialists right now about these issues. They better catch up fast when these drugs come out.

 

[Gb3]

No need for violence. Parts of the industry will be in decline while new entrants fill the space as preferred alternatives.

Hearing aids and other coping treatments will just slowly start to go extinct and become a niche player like the cassette tape and dial-up internet.

I would compare this to eye glasses and LASIK. There are a lot of people who have hearing loss and tinnitus who will not seek this treatment because it just isn't that bothersome to them. Just like in comparison people who continue to use eye glasses or contacts instead of getting LASIK surgery.

 

[Philip83]

Agree. I largely think this "above 8 kHz doesn't matter" has the hearing aid industry partly to blame. They can't provide a product to meet the need so conditioned the market that it is not important.

I was at an audiologist yesterday because I want to make moulded earplugs. He was actually quite knowledgeable and we talked a bit about extended audiograms. He told me one reason that it's not often that over 8 kHz and below 250 Hz is done is because of technical issues in getting correct results. The higher the frequency, the more likely that the ear canal, which is differently shaped for every person, will possibly interfere with the signal, as higher frequency sound waves are more sensitive to obstruction when reaching the eardrum. And the lower the frequency, the more important the seal of the headphones that are used becomes, and even just a slight opening will make the sound "escape" and not hit your ear properly.

That's what he said anyways, and I think it seems like it makes sense. He wasn't denying that frequencies outside the normal testing range matters, just that they are harder to test accurately.

 

[FGG]

I was at an audiologist yesterday because I want to make moulded earplugs. He was actually quite knowledgeable and we talked a bit about extended audiograms. He told me one reason that it's not often that over 8 kHz and below 250 Hz is done is because of technical issues in getting correct results. The higher the frequency, the more likely that the ear canal, which is differently shaped for every person, will possibly interfere with the signal, as higher frequency sound waves are more sensitive to obstruction when reaching the eardrum. And the lower the frequency, the more important the seal of the headphones that are used becomes, and even just a slight opening will make the sound "escape" and not hit your ear properly.

That's what he said anyways, and I think it seems like it makes sense. He wasn't denying that frequencies outside the normal testing range matters, just that they are harder to test accurately.

I was also told the same for below 125 Hz and above 12000 Hz. Up to 12000 Hz can be done accurately and is done at many Otologist practices (because it's often done when monitoring chemo) but isn't universal because of the limitations of hearing aids.

Up to 16000 Hz can be done accurately too (hence why Frequency Therapeutics is doing it) but needs a lot more calibration.

 

[antonio77]

Will FX-322 work for those who got tinnitus from benzodiazepine use?

 

[Lucifer]

Will FX-322 work for those who got tinnitus from benzodiazepine use?

I would say FX-322 will work with those that acquired tinnitus from benzodiazepines.

It most likely won't help those that have tinnitus due to stress or TMJ.

 

[FGG]

Will FX-322 work for those who got tinnitus from benzodiazepine use?

FX-322 regrows hair cells so it will help if you have hair cell loss. It's not a general tinnitus drug.

Hair cell loss isn't the mechanism of action for benzo induced tinnitus. However, if you had hair cell loss and the benzos worsened the tinnitus from the structural deficit, I could see it being helpful.

 

[tbuzz89]

It most likely won't help those that have tinnitus due to stress or TMJ.

I thought mine was due to stress when I first got it back in March. Looking back, I really don't see how stress in and of itself can be a cause. However, being under severe stress and suffering an acoustic trauma can definitely trigger tinnitus. I'm now under the belief that "stress induced" tinnitus still has roots in acoustic trauma and or long term noise exposure wheres stress may have acted as a trigger while exposed to more of whatever the long term noise was, e.g., earbuds and loud music.

I won't speak on TMJ as I don't know enough about the physical relationship to tinnitus and subsequent treatments.

My guess is that most people who claim their tinnitus was caused by stress most likely suffered from some form of acoustic related damage and thus FX-322 may be effective. Results in March/May pending, of course.

 

[weab00]

Agree. I largely think this "above 8 kHz doesn't matter" has the hearing aid industry partly to blame. They can't provide a product to meet the need so conditioned the market that it is not important.

It's just crazy how an audiologist can tell you that frequencies above 8 kHz are irrelevant to your hearing when it's information that can be readily accessed on Google.

That's what he said anyways, and I think it seems like it makes sense. He wasn't denying that frequencies outside the normal testing range matters, just that they are harder to test accurately.

My AuD legit told me it didn't matter; I think this is the case for many people here as well.

 

[AfroSnowman]

@FGG I am just asking for a friend of mine... as a thought experiment. Let's say that your hearing loss/tinnitus was related to a targeted microwave attack (aka Havana syndrome), would you presume the relevancy of FX-322 as a treatment would be the same as noise-induced hearing loss? The hypothetical damage of my friend looked a lot like, but a little bit different, to being exposed to a bomb or gun blast.

 

[Street Novelist]

I wish we could get someone from Frequency Therapeutics to answer some questions. I know they can't, but the wait is excruciating. There's a chance they release the results in March/May and nothing happens. We might have to wait until 2022. 2021 could be a throwaway. I wish we knew what was going on behind the scenes between them and the FDA.

 

[Lucifer]

I wish we could get someone from Frequency Therapeutics to answer some questions. I know they can't, but the wait is excruciating. There's a chance they release the results in March/May and nothing happens. We might have to wait until 2022. 2021 could be a throwaway. I wish we knew what was going on behind the scenes between them and the FDA.

If there is any chance they can release FX-322 quicker, Frequency Therapeutics will use that opportunity.

If results are positive in March/May they will definitely get Breakthrough Therapy status but what we don't know is how much time gets shaved off by getting Breakthrough Therapy status.

 

[FGG]

@FGG I am just asking for a friend of mine... as a thought experiment. Let's say that your hearing loss/tinnitus was related to a targeted microwave attack (aka Havana syndrome), would you presume the relevancy of FX-322 as a treatment would be the same as noise-induced hearing loss? The hypothetical damage of my friend looked a lot like, but a little bit different, to being exposed to a bomb or gun blast.

When you say "it looks a lot like" do you mean audiogram?

 

[AfroSnowman]

When you say "it looks a lot like" do you mean audiogram?

Yes. In this hypothetical a big old bilateral notch which eventually healed but left the tinnitus behind.

 

[serendipity1996]

If there is any chance they can release FX-322 quicker, Frequency Therapeutics will use that opportunity.

If results are positive in March/May they will definitely get Breakthrough Therapy status but what we don't know is how much time gets shaved off by getting Breakthrough Therapy status.

Yeah, I hope so. Chris Loose said recently in that webinar that they "are working as hard and fast as they possibly can" and I am pretty sure Carl LeBel echoed that sentiment in the Tinnitus Talk Podcast.

 

[FGG]

Yes. In this hypothetical a big old bilateral notch which eventually healed but left the tinnitus behind.

So... are you saying there was a large notch and it resolved fully?

Hard to say because I have no idea what the mechanism would be but if the audiogram rebounded, I would guess there are still good support cells. If any hair cell loss remains (residual OHC or IHC that didn't heal because this wouldn't show up on audiogram), it should help.

If there is some other problem unique to this, e.g. secondary hydrops for example, obviously it wouldn't help. It's worth a try though!

 

[FGG]

I made a thing.

 

[Bill Arsenault]

FX-322 regrows hair cells so it will help if you have hair cell loss. It's not a general tinnitus drug.

Hair cell loss isn't the mechanism of action for benzo induced tinnitus. However, if you had hair cell loss and the benzos worsened the tinnitus from the structural deficit, I could see it being helpful.

I realize this is not a benzos thread - I'm just hoping for a yes or no on that one.

My main question is about synapses, ototoxicity and FX-322.

Does tinnitus specifically from benzos appear to be different in some ways than straight-up ototoxicity from some of the other usual suspects?
Maybe the withdrawal process and GABA levels among other things come into play and that's what you are referring to as possibly being the primary mechanism of action.

I've lost all of my hearing above 10 kHz very rapidly over the last few years and in correlation with worsening tinnitus in those lost frequencies.

For simplicity's sake let's assume that it's all primarily from non-benzo ototoxicity (not age-related or noise-induced) although Xanax was certainly part of the concoction.

My hearing below 10 kHz is adequate and seems to have remained unchanged during that time and I have no tinnitus tones at those frequencies.

I'm sure I have structural deficits down there but It is not an issue yet.
I have had two normal audiograms a year apart as standard procedure before seeing an ENT, but have yet to ask for the results.
I was scheduled for an extended one before COVID-19 hit.
That's the one I'm interested in.

Christ - let me just get to the point.

Does this sound like just hair cell damage or does severe ototoxicity issues often damage synapses too?
Or are damaged synapses more of a noise-induced issue?

If FX-322 proves to be exceptionally effective at restoring the higher frequencies by promoting hair cell growth where there is damage up there, then maybe I fall pretty well into that category and I don't need to be concerning myself too much about synapses.
Although instinctively I feel like damage to synapses has also occurred even though I have no clue what they are yet.

The other hand would be that I should also be reading about those other drugs that target synapses and learn what synapses even are and do.
Currently I barely even grasp the IHC/OHC stuff.
You people are amazing at helping everyone understand things.
I'm just a notoriously slow learner.

Thanks for any insight.
Take care.

 

[FGG]

I realize this is not a benzos thread - I'm just hoping for a yes or no on that one.

My main question is about synapses, ototoxicity and FX-322.

Does tinnitus specifically from benzos appear to be different in some ways than straight-up ototoxicity from some of the other usual suspects?
Maybe the withdrawal process and GABA levels among other things come into play and that's what you are referring to as possibly being the primary mechanism of action.

I've lost all of my hearing above 10 kHz very rapidly over the last few years and in correlation with worsening tinnitus in those lost frequencies.

For simplicity's sake let's assume that it's all primarily from non-benzo ototoxicity (not age-related or noise-induced) although Xanax was certainly part of the concoction.

My hearing below 10 kHz is adequate and seems to have remained unchanged during that time and I have no tinnitus tones at those frequencies.

I'm sure I have structural deficits down there but It is not an issue yet.
I have had two normal audiograms a year apart as standard procedure before seeing an ENT, but have yet to ask for the results.
I was scheduled for an extended one before COVID-19 hit.
That's the one I'm interested in.

Christ - let me just get to the point.

Does this sound like just hair cell damage or does severe ototoxicity issues often damage synapses too?
Or are damaged synapses more of a noise-induced issue?

If FX-322 proves to be exceptionally effective at restoring the higher frequencies by promoting hair cell growth where there is damage up there, then maybe I fall pretty well into that category and I don't need to be concerning myself too much about synapses.
Although instinctively I feel like damage to synapses has also occurred even though I have no clue what they are yet.

The other hand would be that I should also be reading about those other drugs that target synapses and learn what synapses even are and do.
Currently I barely even grasp the IHC/OHC stuff.
You people are amazing at helping everyone understand things.
I'm just a notoriously slow learner.

Thanks for any insight.
Take care.

Here are my thoughts based on what appears to be known in the literature, but benzo induced tinnitus is very, very complex.

Benzo induced tinnitus is not like typical ototoxicity where it destroys cochlear structures like hair cells. They do not (except in severe cases like GABA receptor knock out mice who have specific deletions of subtypes, but this is not something even someone with severe benzo issues should have).

Benzo tolerance or inappropriate withdrawal results in GABA receptor changes. You have GABA receptors in your cochlea and in your central nervous system.

GABAs role in hearing is complex. The GABA receptors in your cochlea have a functional role in OHC motility and function:

Effect of acetylcholine and GABA on the transfer function of electromotility in isolated outer hair cells

In this sense, it appears benzos can alter the function of otherwise normal hair cells.

However, there are also central auditory benzo receptors and they can dampen tinnitus perception centrally (or heighten it during tolerance). In these cases, there is another underlying cause that benzos are effecting /attenuating centrally. This is why benzos are helpful for many people, regardless of cause unless tolerance or inappropriate withdrawal happens. Anyway, in this case, treating the underlying cause (if it's hair cell loss), should help this aspect.

TL;DR: FX-322 should help at least somewhat if there are lost hair cells.

 

[Gb3]

If there is any chance they can release FX-322 quicker, Frequency Therapeutics will use that opportunity.

If results are positive in March/May they will definitely get Breakthrough Therapy status but what we don't know is how much time gets shaved off by getting Breakthrough Therapy status.

That's probably why they are going to release early results.

 

[Princebeyel]

Do you think FX-322 could also treat issues with balance?

 

[Aleksandar]

I hope the FX-322 will help with the tinnitus and some hearing lost I got from covid-19

 

[aot]

I made a thing.

View attachment 42132

You have nice handwriting.

 

[frpp]

Do you think FX-322 could also treat issues with balance?

Maybe. Hearing and balance do go together. When my TTTS acts up I do get some disequilibrium.

 

[tiredofit]

Not cool news for people with born hearing loss to be honest.

 

[frpp]

Not cool news for people with born hearing loss to be honest.

Do they know the cause? I think Decibel Therapeutics and Rinri Therapeutics are working on a couple of projects for those who are born deaf.

 

[wwtsai]

Not cool news for people with born hearing loss to be honest.

I think it really depends what exactly is being affected regarding hereditary/genetic hearing loss. If the defective gene is associated with hair cell development/life then I could see FX-322 still having some effect. If the gene affects something else such as mitochondria then FX-322 wouldn't help. It's been shown that many genes play a role in hearing loss.

 

[FGG]

Do you think FX-322 could also treat issues with balance?

FX-322 isn't likely to help imo but vestibular hair cells are being heavily researched for regeneration. In fact, Decibel Therapeutics has drugs in pre-clinical for this.

 

[FGG]

You have nice handwriting.

That... must be sarcasm .

True story, a nice bonus when I got my doctorate was that I no longer wrote like a 4th grader or a serial killer and just had "doctor's handwriting."

 

[FGG]

I think it really depends what exactly is being affected regarding hereditary/genetic hearing loss. If the defective gene is associated with hair cell development/life then I could see FX-322 still having some effect. If the gene affects something else such as mitochondria then FX-322 wouldn't help. It's been shown that many genes play a role in hearing loss.

Right. It depends.

Some people even have normal genetics but had a virus (e.g., Cytomegalovirus) destroy hair cells in utero. Those people could likely be helped well with drugs like FX-322. Technically, that's an acquired loss but it happened before birth.

And to add to this, there is a huge amount of research in treating the genetic causes with viral vectored genetic treatments. See: Akouos and Decibel Therapeutics, for instance, who both have treatments in pre-clinical for certain types of genetic hearing loss. If the abnormal gene can be corrected then structures that were lost prematurely could be potentially regenerated after that point. It sounds like science fiction but there are a whole host of diseases they are now tackling in this way, most recently using genetic editing to cure Sickle Cell.

Genetic conductive conditions (e.g., Middle ear disease) or cochlear malformation etc would obviously be different, though.