Frequency Therapeutics — Hearing Loss Regeneration

[GlennS]

I presume there are forces out there, i.e. interested parties like the hearing aid industry, that will do everything in their power to make sure FX-322 doesn't hit the market, or if it does, to make sure it fails somehow.

Frequency Therapeutics is already a public company. If this were a "water car" situation (not that I believe in that tinfoil theory) then wouldn't you want to stop it long before it reached this point? I would not try concocting conspiracies here. It's just a way to avoid getting your hopes up.

BTW, for the record, the buggy-whip manufacturers couldn't stop cars and Chevron/Cobasys couldn't stop electric cars, despite the movie. (I'm driving one now, btw). Progress has a way of proceeding anyway.

 

[Billy_Shears]

They can file a lot of petitions to the FDA citing safety concerns and request additional clinical trials before the product enters the market. I think all they can do is delay the process.

One good thing that might happen is that they might have an incentive to lower the price of hearing aids, so that they remain competitive.

FX-322 was proven to be safe during the initial trial so any petitions or requests for additional trials from anyone other than a group of medical professionals in the field (and even these cherished folks) will fall on deaf ears, pardon the jocular pun.

Hearing aid companies AND audiologists are not even in the theatre concerning cochlea pharmacology. There is no industry or outside forces that will incumber the success of FX-322 and its availability to all who need it.

 

[sssing]

Neuroplasticity is not stuck in one direction. Just as in phantom limb, if you use mirror therapy, you can affect the maladaptive plasticity. Unfortunately, there is no "mirror therapy" with the cochlea.

If tinnitus caused a permanent brain change no one would recover from it and people would not have fluctuating tinnitus with hydrops treatment or improvements from TMJ treatment. If you fix the underlying cause (when possible), tinnitus responds. That would not be true if maladaptive plasticity was permanent.

As far as visual snow, it's so much more poorly understood.

What is known is that a lot of people with visual snow never have tinnitus (some people are born with visual snow) and a lot of people with tinnitus never get visual snow. It seems genetic or at least congenital in some people (some people recall always having it) but in others it seems to result also from maladaptive neuroplasticity after getting things like tinnitus.

It's hard to say exactly what effect tinnitus treatment would have on visual snow but it seems to have a thalamus connection according to many researchers. The thalamus is a particularly plastic part of the brain and I think restoring normal input would probably help visual snow is well. This question is looking to be answered within the next 5 years it looks like though.

Could it be tinnitus sufferers' brains are somehow not as plastic as those who have recovered?

Rather than the cochlear recovering and the brain responding to that recovery, it could be the brain was already compromised and therefore the insult from the cochlear triggers it. So the problem might lie partly in the brain as well? I'm saying this as hearing loss and brain degeneration seems to have some correlation.

I'm just guessing because things like stress, sleep, etc affect tinnitus.

 

[tommyd87]

I don't see how a 3rd party does that either.

But I'm also not sure FX-322 has "already proven to be extremely safe and also almost risk free."

It's shown that in a small number of people with severe hearing damage, it was safe, and safe enough to proceed to a larger Phase II trial. But there are drugs that progress from Phase I to II to III, each with progressively larger numbers of participants, that only show dangerous side effects in Phase III.

Just look at the recent AstraZeneca COVID-19 vaccine trial that seemed to cause a serious neurological reaction only once it progressed to tens of thousands of participants in Phase III. And still other drugs manifest side effects only after they've been released into the marketplace. I forget the name of it, for example, but there was a drug I read about in this forum that helped some people with tinnitus, was FDA approved, and taken off the market due to serious side effects that showed up only after it was in the market for a few years.

The sheer length of this thread is a testament to how hopeful we all are that FX-322 will help us, and how eager we all are to try it. I mean, hell yeah, sign me up! Given the suffering, I'm eager to take it as soon as I can if it continues to generate good results. But if I'm fortunate enough to get access to it as part of a compassionate use program before it's completed a Phase III trial, there's still unknown risk. I'm no less a guinea pig than any other guinea pig in the trial.

From what I understand about the AstraZeneca COVID-19 trial, the reason for the vaccine halt has not been confirmed yet. From what I have seen, the negative reaction had by that participant could have been caused by the placebo and/or an underlying condition which the participant has but has not been identified as yet. I also believe that there is still no conclusive connection between the vaccine and the unfortunate adverse reaction that this person had.

Retigabine has had some adverse affects and got withdrawn from the market. My understanding is that Retigabine is now being redone/reformulated to remove the adverse elements and make it suitable for use again.

From what I understand FX-322 is a very low risk medicine compared to others and has demonstrated this to be the case thus far. However I don't disagree with you that it is entirely possible that there could be adverse outcomes and/or experiences from this in the future.

 

[FGG]

Could it be tinnitus sufferers' brains are somehow not as plastic as those who have recovered?

Rather than the cochlear recovering and the brain responding to that recovery, it could be the brain was already compromised and therefore the insult from the cochlear triggers it. So the problem might lie partly in the brain as well? I'm saying this as hearing loss and brain degeneration seems to have some correlation.

I'm just guessing because things like stress, sleep, etc affect tinnitus.

Your question has two parts and I will give you thoughts on both.

First, it's incredibly complicated how things like stress affects tinnitus but it's a neurotransmitter issue and not because people have brain damage. I have included diagrams of the brain's neurotransmitter response to "uncoping stress" vs "coping stress" and you can see the neurotransmitter profiles are really different.

These were taken from Fuad Lechin's book "Neurocircuitry and Neuroautonomic Disorders" who is a researcher who was once nominated for the Nobel Prize in medicine. Highly recommend his book but fair warning it is very technical and dense.

Anyway, what he discovered many years ago is that the brain directly controls immune/inflammatory response by pushing it toward either TH1 or TH2 predominant state (basically which kind of helper T cell predominates so which kind of inflammatory cytokines, or messengers, predominant).

As to your other point that maybe sufferers have brains that don't recover when the cochlea recovers, those people that didn't recover didn't have cochleas that recovered. If their brain responded to the abnormal input, it would respond to the normalized input. Plasticity isn't an on/off switch that gets broken off. If they didn't have plastic brains, they shouldn't have had maladaptively plastic brains either.

 

[tarmaced]

I'm just guessing because things like stress, sleep, etc affect tinnitus.

They can impact your handling of ANY challenging stimulus.

 

[sensualmosquito]

I hope that I can eventually get at least some of my hearing back, if not all of it. I notice my hearing loss all the time because it's moderate (~50 dB) in my right ear, while my left is normal. I want to at least feel more normal, and reduce my tinnitus. Who knows if FX-322 would really work on me though, since my case began with one noise exposure instead of the numerous ones that typically cause tinnitus and NIHL for people. My ear could be pretty jacked up structurally, so I don't know. Maybe I'll have to wait until I can get an ear transplant (I'll be long gone until that's possible lol).

 

[serendipity1996]

I hope that I can eventually get at least some of my hearing back, if not all of it. I notice my hearing loss all the time because it's moderate (~50 dB) in my right ear, while my left is normal. I want to at least feel more normal, and reduce my tinnitus. Who knows if FX-322 would really work on me though, since my case began with one noise exposure instead of the numerous ones that typically cause tinnitus and NIHL for people. My ear could be pretty jacked up structurally, so I don't know. Maybe I'll have to wait until I can get an ear transplant (I'll be long gone until that's possible lol).

I don't think FX-322 would be less liable to work if you got hearing loss from a 'one-off' incident, at the end of the day it is still NIHL which is what FX-322 is intending to fix.

 

[tommyd87]

I hope that I can eventually get at least some of my hearing back, if not all of it. I notice my hearing loss all the time because it's moderate (~50 dB) in my right ear, while my left is normal. I want to at least feel more normal, and reduce my tinnitus. Who knows if FX-322 would really work on me though, since my case began with one noise exposure instead of the numerous ones that typically cause tinnitus and NIHL for people. My ear could be pretty jacked up structurally, so I don't know. Maybe I'll have to wait until I can get an ear transplant (I'll be long gone until that's possible lol).

I really think right now that there isn't any difference between whether the hearing loss was caused by a single incident or where it was caused progressively. In fact if I look at what those in the restorative medicine space have suggested about hearing loss (like Hough Ear Institute), I would actually suggest that the fact that they have referred to army issues means that they think it is no different.

I would actually argue there is no difference because a lot of outcomes from research suggests that hearing loss is the same. You simply have just lost hair cells or synapses and you need to get these repaired to regain hearing.

I actually think that these treatments might actually dispel some of those conditions around hearing loss which have been coined by experts. One example is Acoustic Shock which certain parties believe is now just really a single situation where you lost hair cells. it isn't just some specific condition like it has been made out as.

I think that if synapse treatment ends up resolving your issue with reduced synapses then no matter how bad they are or how this occurred you should regain regular hearing function.

For now we are still hypothesising, however I think that the evidence is fairly promising and positive that this treatment will (providing the lab outcomes replicate in an ear) restore regular hearing function. It is now just a matter of waiting for the conclusion of trials.

 

[Pete88]

I hope that I can eventually get at least some of my hearing back, if not all of it. I notice my hearing loss all the time because it's moderate (~50 dB) in my right ear, while my left is normal. I want to at least feel more normal, and reduce my tinnitus. Who knows if FX-322 would really work on me though, since my case began with one noise exposure instead of the numerous ones that typically cause tinnitus and NIHL for people. My ear could be pretty jacked up structurally, so I don't know. Maybe I'll have to wait until I can get an ea'r transplant (I'll be long gone until that's possible lol).

I dont think it matters if it was one big bang or several minor instances of damage. If it's hair cell loss, FX-322, assuming it indeed works, can fix it.

I crept on your profile and you stated your hearing loss is 6-8 kHz. Lucky for you, FX-322 helped 8 kHz and I bet can penetrate to at least 6 kHz with multiple dosing.

Just be patient. I know it sucks but you have only good reason to be hopeful that you can be fixed up, at least to a certain extent, in a few years!

 

[serendipity1996]

Even if your hearing loss comes from a one-off incident that could have just been the straw that broke the camel's back, so to speak.

 

[FGG]

I really think right now that there isn't any difference between whether the hearing loss was caused by a single incident or where it was caused progressively. In fact if I look at what those in the restorative medicine space have suggested about hearing loss (like Hough Ear Institute), I would actually suggest that the fact that they have referred to army issues means that they think it is no different.

I would actually argue there is no difference because a lot of outcomes from research suggests that hearing loss is the same. You simply have just lost hair cells or synapses and you need to get these repaired to regain hearing.

Along these lines, the cause shouldn't matter but rather what structures are affected is what's important.

If you break an arm falling off a tree or in a car wreck, would you treat it differently?

If you get cataracts from age or diabetes, is the treatment different?

Cause only matters if the physiological or structural outcome is different.

@sensualmosquito, if you have a 50 dB loss on your audiogram, it means you, for sure, lost OHCs so you need a hair cell regenerating drug for that problem.

 

[tommyd87]

I dont think it matters if it was one big bang or several minor instances of damage. If it's hair cell loss, FX-322, assuming it indeed works, can fix it.

I crept on your profile and you stated your hearing loss is 6-8 kHz. Lucky for you, FX-322 helped 8 kHz and I bet can penetrate to at least 6 kHz with multiple dosing.

Just be patient. I know it sucks but you have only good reason to be hopeful that you can be fixed up, at least to a certain extent, in a few years!

Frequency Therapeutics have said somewhere in one of their slide releases that they can get FX-322 to work down to 6500 Hz. We know how conservative Frequency Therapeutics has been with the information they have released. Thus I am absolutely positive that if they hadn't been certain that this could be done then they would not have made this claim. Therefore I would totally expect that we would see benefit be gained here and hopefully in the even lower frequencies too.

 

[weab00]

I really think right now that there isn't any difference between whether the hearing loss was caused by a single incident or where it was caused progressively. In fact if I look at what those in the restorative medicine space have suggested about hearing loss (like Hough Ear Institute), I would actually suggest that the fact that they have referred to army issues means that they think it is no different.

I would actually argue there is no difference because a lot of outcomes from research suggests that hearing loss is the same. You simply have just lost hair cells or synapses and you need to get these repaired to regain hearing.

I actually think that these treatments might actually dispel some of those conditions around hearing loss which have been coined by experts. One example is Acoustic Shock which certain parties believe is now just really a single situation where you lost hair cells. it isn't just some specific condition like it has been made out as.

I think that if synapse treatment ends up resolving your issue with reduced synapses then no matter how bad they are or how this occurred you should regain regular hearing function.

For now we are still hypothesising, however I think that the evidence is fairly promising and positive that this treatment will (providing the lab outcomes replicate in an ear) restore regular hearing function. It is now just a matter of waiting for the conclusion of trials.

I thought that a sudden acoustic trauma made it more likely for you to develop hyperacusis because it inflames the inner ear? Whereas hearing loss is progressive and thus not inflammatory. Seems like I'm completely wrong based on other replies but I don't know why I had a disconnect in thinking that.

 

[FGG]

I thought that a sudden acoustic trauma made it more likely for you to develop hyperacusis because it inflames the inner ear? Whereas hearing loss is progressive and thus not inflammatory. Seems like I'm completely wrong based on other replies but I don't know why I had a disconnect in thinking that.

I think you are right that sudden hearing loss would be more acutely inflammatory but it shouldn't affect whether FX-322 regrows hair cells and that was @sensualmosquito's worry.

 

[serendipity1996]

I thought that a sudden acoustic trauma made it more likely for you to develop hyperacusis because it inflames the inner ear? Whereas hearing loss is progressive and thus not inflammatory. Seems like I'm completely wrong based on other replies but I don't know why I had a disconnect in thinking that.

I don't think whether you get hyperacusis comes down to sudden vs gradual onset - my onset of hyperacusis/noxacusis was gradual. I think those of us who were predisposed to developing hyperacusis would have developed it with either a gradual or sudden hearing damage.

 

[tommyd87]

I thought that a sudden acoustic trauma made it more likely for you to develop hyperacusis because it inflames the inner ear? Whereas hearing loss is progressive and thus not inflammatory. Seems like I'm completely wrong based on other replies but I don't know why I had a disconnect in thinking that.

I don't disagree with the theory that a single acoustic shock could cause hyperacusis.

The theory that your ear gets inflamed from an acoustic shock seems fairly plausible and also fairly logical. However I also think that repeated impact from loud noise will also actually cause inflammation and can probably also cause hyperacusis.

The fact is that you can inflame your body from a single action such as straining your calf muscle whilst turning playing soccer or you can inflame your calf muscle from too much running on it over the course of a game of soccer...

It is therefore possible that if hyperacusis is caused by inflammation, it could be caused by both a single and repeat exposure to loud noise(s). This is because you could probably inflame your cochlear(s) either way.

 

[dan]

@FGG do you think that if FX-322 is successful, then other companies will join the research for further hearing regeneration, to directly compete with what Frequency Therapeutics is working on?

 

[serendipity1996]

I don't disagree with the theory that a single acoustic shock could cause hyperacusis.

The theory that your ear gets inflamed from an acoustic shock seems fairly plausible and also fairly logical. However I also think that repeated impact from loud noise will also actually cause inflammation and can probably also cause hyperacusis.

The fact is that you can inflame your body from a single action such as straining your calf muscle whilst turning playing soccer or you can inflame your calf muscle from too much running on it over the course of a game of soccer...

It is therefore possible that if hyperacusis is caused by inflammation, it could be caused by both a single and repeat exposure to loud noise(s). This is because you could probably inflame your cochlear(s) either way.

Perhaps this is slightly different but I recall the 2015 Johns Hopkins paper on noxacusis stating that even progressive, gradual damage can increase levels of ATP in the cochlea - the ATP is suspected to possibly be what causes pain, as it leaks from damaged OHCs and surrounding support cells.

"Such immediate rupture of individual hair cells might occur in vivo. More commonly, however, acoustic stress progressively damages OHCs, leading to their eventual death, and is known to increase ATP concentration in cochlear fluids in vivo."

https://www.pnas.org/content/112/47/14723

 

[FGG]

@FGG do you think that if FX-322 is successful, then other companies will join the research for further hearing regeneration, to directly compete with what Frequency Therapeutics is working on?

They already are. Otonomy has a drug in pre-clinical that addresses "severe hearing loss" so they are targeting more severe loss it sounds like. What their method entails is unknown but hopefully more info will be out soon.

Akouos also has a drug in pre-clinical but for now they are focused on genetic deafness.

 

[dan]

They already are. Otonomy has a drug in pre-clinical that addresses "severe hearing loss" so they are targeting more severe loss it sounds like. What their method entails is unknown but hopefully more info will be out soon.

Akouos also has a drug in pre-clinical but for now they are focused on genetic deafness.

Yes thanks for your response as always. I'm wondering do you think there would be more companies (not just 2 more), like a dozen or so... for example like we have many types of pain med companies and manufacturers...

 

[weab00]

They already are. Otonomy has a drug in pre-clinical that addresses "severe hearing loss" so they are targeting more severe loss it sounds like. What their method entails is unknown but hopefully more info will be out soon.

Akouos also has a drug in pre-clinical but for now they are focused on genetic deafness.

Wondering if these are truly exciting times for sensorineural hearing loss/tinnitus or if it'll wind up being the age-old "5 years away from a cure."

 

[FGG]

Yes thanks for your response as always. I'm wondering do you think there would be more companies (not just 2 more), like a dozen or so... for example like we have many types of pain med companies and manufacturers...

Almost for sure there are but we won't hear about them until they are about to start trials. It's still a new field.

 

[d'Wooluf]

Almost for sure there are but we won't hear about them until they are about to start trials. It's still a new field.

For sure:

e.g., Drug delivery to treat hearing loss

 

[tommyd87]

Yes thanks for your response as always. I'm wondering do you think there would be more companies (not just 2 more), like a dozen or so... for example like we have many types of pain med companies and manufacturers...

The issue is that if a pharma company comes up with a successful treatment, they will obtain a patent which will allow them to have exclusive use of that treatment for 20 years. Therefore this means that a competitor cannot copy their treatment during this time. Thus any other treatments in this space will have to be novel in either their approach or their pharmaceutical make up too.

The Nasonex spray (which provides relief from sinus/polyp breathing problems) is a good example of the effects of how a patent influences medicine manufacturing. Many companies could copy this medicine, however they could not make it in a way which did not infringe on the patent. Thus for years Nasonex was the only manufacturer and the price was high. Recently this patent expired and more companies started making their own version and this means more options.

I think that a situation similar to the Nasonex situation is likely with medicines treating hearing matters. Unless pharma companies can come up with like 10 different ways to achieve the same outcome, there is likely to be a limit as to how many companies can offer treatment at this time. There is also the other negative impost of having to put the medicine through the trial process too. I cannot see pharma companies being keen to invest big money on coming up with a medicine to compete with those already in the market unless they truly believe that their treatment will provide better results.

Thus I strongly believe that there will be only a few companies offering treatment now and obviously many more shall make entry into the market after the patents start to expire. Having the patent expired means pharma companies can quite often bypass a lot of the expensive entry costs.

 

[Billy_Shears]

Frequency Therapeutics have said somewhere in one of their slide releases that they can get FX-322 to work down to 6500 Hz. We know how conservative Frequency Therapeutics has been with the information they have released. Thus I am absolutely positive that if they hadn't been certain that this could be done then they would not have made this claim. Therefore I would totally expect that we would see benefit be gained here and hopefully in the even lower frequencies too.

I would not be surprised that by 2025, in the aftermath of the release of FX-322, a year or two prior, the delivery will be successfully modified to treat all frequencies, thereby, finally curing sensorineural hearing loss and tinnitus that is caused by this type of hearing loss. What a wonderful thought if I may say so, and very realistic.

 

[all to gain]

Wondering if these are truly exciting times for sensorineural hearing loss/tinnitus or if it'll wind up being the age-old "5 years away from a cure."

The pessimist in me agrees, but at the same time I can't help but get excited by FX-322.

I didn't get this feeling from Lenire at all.

September seemed to take forever to come around, but now waiting until mid-2021 for the results is excruciating to say the least.

 

[tomytl]

It's an exciting time for regenerative medicine for the inner ear.

But as of today, we still have no insight what exactly happened with Novartis Atoh1, with Audion LGR-5 or with Frequency Therapeutics' FX-322 trials.

Just imagine if there was a single treatment capable of regenerating outer or inner hair cells, the field would explode. Almost all of the "inner ear" focused companies have a hair cell regeneration program in their pipeline.

Further there has been so many discoveries in the last few years that it's likely that some day we will have a robust way to treat sensorineural hearing loss.

 

[Gabriel5050]

I also wouldn't mind people slowing down with posting in this thread and do so only when new information actually comes up. I don't think this is the place for discussing things like stock trades as I remember seeing here.

 

[serendipity1996]

I also wouldn't mind people slowing down with posting in this thread and do so only when new information actually comes up. I don't think this is the place for discussing things like stock trades as I remember seeing here.

FX-322 is probably the most exciting prospect in the hearing field so there's bound to be a lot of speculations plus questions and answers that people may have whilst we wait for new information.