Frequency Therapeutics — Hearing Loss Regeneration

To be honest, I'm still getting my head around all this so I really appreciate your detailed and thorough response. Yeah, I think there's a possibility that cochlear damage could then trigger middle ear hyperactivity as a consequence, as per the Liberman paper. I think if that's the case then there's reason to be hopeful that FX-322 could help. I posted an article a while ago on 'Neuroplasticity and Pain' and here's another written by the same author (who has written extensively on this topic) on 'Persistent Pain as a Disease Entity.'

https://journals.lww.com/anesthesia...ain_as_a_Disease_Entity__Implications.37.aspx

Under the sub-heading, 'Pain as a Secondary Disease', he states:

"In describing all these changes, it has been suggested that the induction of these changes leads to a state in which the perception of pain is maintained independently of inputs to the nervous system. While it is tempting to speculate that this is indeed the case in people who have persistent pain despite no evidence of pathology, there is little evidence to support this proposition. A hip replacement will usually lead to a substantial reduction, if not elimination, of pain arising from an osteoarthritic hip, no matter how long the pain has been present. Secondary pathological changes, such as central sensitization, mood changes, and disability, may occur as a result of persistent nociceptive inputs. However, they will generally all resolve after a procedure that results in resolution or removal of the underlying primary pathology."

I'm approaching this with no scientific or medical background but this seems encouraging to me and perhaps indicates that if you get rid of the underlying pathology (damaged cochlea with FX-322) then it could have a positive effect and the middle ear symptoms could 'normalise' over time. So, it seems to suggest that it's unlikely that the pain would end up becoming a self-perpetuating mechanism if you were to fix the underlying primary pathology (assuming the culprit is a damaged inner ear).

I think your second part about whether the middle-ear is directly affected though is intriguing and is a very real possibility though. One thing I wonder - is it possible to determine if your middle-ear or TTM is damaged? Can that be observed by a clinician? One thing that I experience personally that is strange is that my facial pain was primarily isolated on the left side of my face yet my right ear is the one that will 'spasm' slightly if I trigger it by shutting one eye.

If the problem resides in the middle ear my question is how do we fix it? Can the tensor tympani be repaired? If there's inner ear damage we know that restoring the hair cells and synapses will solve it, but the middle ear seems so complex.

 

The inflammation aspect has always puzzled me. I’m seven months in since an acoustic trauma and ear infection combo that gave me unilateral tinnitus/reactive tinnitus.

The intensity of my tinnitus varies daily. My weekly trend now seems to be two tolerable days, two medium days, and three severe days.

If cochlear inflammation is playing a role on top of high-frequency damage or synaptopathy, would that be addressed by FX-322?

 

I doubt it has an anti-inflammatory effect (but who knows), but Sound Pharma is super promising in this regard.

 

That’s right. I know the compound they are in Phase 3 for isn’t regenerative, but if it can at least take down inflammation and decrease intensity fluctuations, that would be extremely helpful to aid many of us over until FX-322 and other regenerative therapeutics are available.

 

I don't really have any other symptoms - at least none that aren't explained by other issues I have (something is up with my neck - I suffered whiplash and my neck is still very stiff and incorrectly posed. I also suspect I have TMJD mostly on the right side predating my tinnitus by at least a year). But as for noise and/or hearing issues, I only have tinnitus.

It does fluctuate, but randomly. It's not day-by-day, or every few days. It changes as it wants to, regardless of noise exposure. I think it's got something to do with my neck and/or blood-pressure. It can change with certain neck movements, and always gets a little worse as soon as I get up in the morning even if that's just sitting on my bed (as opposed to lying down, when it always quietens down some). That, or it's just some kind of frequency-specific reactive tinnitus.

As for setbacks, I haven't had a single one. Even though my tinnitus fluctuates pretty randomly, I've never had a period lasting more than a few minutes it was much worse than average. Again, these can occur from just turning around in bed sometimes.

My tinnitus seemed to improve a little with physical therapy, but the effect was always short-lived. Both for my tinnitus and my neck issues, unfortunately.

Ultimately though, I think many of us will need a combination of treatments - hair cells, synapses, and perhaps even one that lessens inflammation or reduces brain hyperactivity.

 

I know people say that pulsatile tinnitus has nothing to do with hearing damage, however I only started getting frequent fleeting pulsatile tinnitus after my ears got considerably worse. I’ve seen many others on the forum with the same experience. I suspect it’s because my ears are more tuned into frequencies I would not have heard before due to a collapsed auditory system.

Does FX-322 have the potential to help with this assuming the root cause of it is the brain trying to compensate for lost input?

 

As it relates to SNHL / NIHL; If we agree that tinnitus, in its many manifestations, is a "phantom" limb symptom of IHC/OHC loss. Then, restoring both IHC/OHC with FX-322 should reduce the symptom as it restores signal to the brain.

 

I was speaking to someone who knows a little bit about this stuff and they suggested that there could be some benefit even with a profound loss. Furthermore they felt that it is quite likely that the treatment then would work regardless of the length of time from that loss to getting the medicine injected. Looking at it they said that there would quite possibly be a benefit because those that had a normal ear should be likely to have the stuff required to make the cells recover once they are fired by getting the medicine.

I agree with this. The question I have is whether we are seeing Sound Pharmaceuticals focus on this treatment first is for the purposes of getting something released to assist with inflammation issues and also to benefit patients until other options are available on the market.

I reckon right now this treatment is looking very promising, particularly for the fact that this is supposedly a suitable medicine for a number of treatments too. Hence the reason Sound Pharmaceuticals is spending so much time and resources taking it through multiple different trials for multiple treatments.

The fact that their treatment is in phase 3 and also that the treatment has shown good promise to date definitely makes me feel confident that it will be effective and will be approved. I think the question now is what condition(s) they proceed with first to get it through the clinical trials. I know that they have sped stuff up on COVID-19 and as a result this may also mean that they prioritise cystic fibrosis because they are similar in nature.

Next I hope Sound Pharmaceuticals start proceeding with their clinical trials for their hearing regeneration treatment.

 

I've got a similar issue. Mostly really loud days and maybe one quieter day in the week. You'd think we'd be prime candidates for someone to study? Examine us on the bad days, examine us on the good days then see what the difference is.

Anyways, all the speculation about FX-322... I hope we can start injecting it soon to see if it actually works for tinnitus. Strange, they can push a coronavirus vaccine through to phase 3 in record time, yet our ears are not so fortunate.

 

The theory that has been persistently floated with tinnitus is that if it is caused due to auditory issues and deficiencies then fixing these will relieve the tinnitus. The evidence thus far supports this when there are conductive issues causing tinnitus. There have been people who have had earwax removed or their drum repair done for example and as a result of fixing the problem that caused a reduction in their hearing, it has alleviated their tinnitus.

There are also examples of people who have used a hearing aid and also noticed actual relief of their tinnitus. Although there is a small subset who use hearing aids and have a conductive hearing loss issue, it is predominately those who have a hair cell issue using hearing aid and noticing tinnitus relief. Thus this supports the claims that those with hearing loss who gain additional auditory stimulation can experience a reduction in tinnitus.

For this reason, there is no reason to think that tinnitus wouldn't improve if it is caused from a hair cell based issue and FX-322 was utilised to recover the hair cells. This is because using FX-322 would provide the same benefit as a hearing aid. Except FX-322 would be providing natural stimulation rather than artificial stimulation.

The simple anecdotal evidence that came out from the inaugural FX-322 trial indicated that tinnitus was improved in multiple participants. Therefore it is likely that FX-322 should assist with tinnitus, although we will need to wait for further results to obtain complete confirmation.

 

Does anyone know of a risk of getting a tumor from FX-322?

 

It depends on a lot of things I think.

If the type II afferents do something to the nervous system when they get sensitized that then causes the mid ear to trigger the symptom cluster then it depends on several things whether or not FX-322 would fix all of it. For what it's worth, type II activation is the only possible logical thing I can think that would conceivably cause this. Hearing loss / tinnitus alone I seriously doubt. But I doubt the whole concept that the cochlea is responsible for initiation anyway because not only do people apparently have this type II sensitization causing noxacusis in just the cochlea, but also mostly I'd have thought people with profound hearing loss would have a lot of OHC damage and type II activation. Why don't these 2 examples get acoustic shock triggered this way though? Unless people with profound hearing loss, are bizarrely affected in a completely different way that doesn't include OHC damage and type II sensitization I also wonder why they don't typically get pain given there should surely be some damage to OHCs? Just like you I have no medical background but this stuff gets me thinking.

There are so many question to ask to try and work out how they could be linked or have the link broken though.

Is the cochlea sending a permanent signal to (forgive me, this is where I know zero but I'm going to assume its broadly the central nervous or autonomic nervous system) that triggers the acoustic shock? Would this signal stop if the OHCs were fixed? If so it suggests FX-322 would fix all as the source of the problem is now fixed.

Does the cochlea send just one signal to the CNS/ANS at the onset of the damage triggering the acoustic shock? If so, is that initial acoustic shock sufficiently damaging the mid ear enough to turn it into a self damaging cycle? Is the TGN nerve / TCC sensitization enough for the the mid ear side of it to effectively forget about the initial cause but then generate its own heightened response cycle within the auditory nerve system independent of the cochlea? (i.e. even if the cochlea was fixed, the mid ear would now have created it's own setback inducing method?) I doubt FX-322 would fix the mid ear problem if this was the case.

Does the cochlea send repeat signals as those specific frequency OHC support cells are stimulated into releasing ATP to sensitized type II's? (is that what causes setbacks at certain high frequencies?). FX-322 could fix this instance because the source of all the problems are repeatedly initiated only by the cochlea.

If there is a any kind of switch in the CNS/ANS then I doubt it's a permanent on switch because tolerance luckily does improve and so that would suggest that the mid ears response to noise does improve over time, for this reason as well I don't think the 'persistent pain' thing comes into this luckily. What the hell triggers it again and again though, a chronic physical injury, something in the nervous system or both? FX-322 I'm hoping will be more than just a permanent cure for some but also a priceless tool to be used to help work out what triggers setbacks for others.

You mentioned about the culprit being the mid ear so another question would be, did acoustic shock cause some damage to maybe the tensor tympani that has become chronic and has trouble healing properly and because of that is causing the heightened response to noise somehow either on it's own, or in combination with a change in the nervous system? Apparently although some people have had an acoustic shock, they don't display the symptoms that would suggest TGN sensitization or setbacks etc. So the degree of damage sustained physically in the initial acoustic shock could also be very significant.

It melts my brain thinking about the possibilities.

As I mentioned though I doubt the above reason that the cochlea being the initiator is the case of an acoustic shock and I logically more steer to thinking that the whole thing is initiated by the tensor tympani's forced over reaction whilst tying to deal with the incoming sound of an acoustic shock. Whether hearing loss or tinnitus were already present or as a result of this acoustic shock, I believe FX-322 will fix that part of it and the resulting damage of the acoustic shock on the mid ear will become the focus. At the very least whatever happens, I think it looks like some hearing loss / tinnitus / modulated tinnitus should hopefully be fixed with FX-322 regardless of whether it was caused by general loud noise exposure or the acoustic shock.

 

I think you may have slightly misread or misunderstood my question. Thank you for the well thought out response anyway but I was more wondering if FX-322 would improve this whooshing sensation I’m experiencing. Basically I only got fleeting pulsatile tinnitus after my hyperacusis/tinnitus got worse and I believe it’s due to less input from the ears and the brain trying to overcompensate. Just a theory though.

 

I don't think anyone knows. It's not a stem cell therapy, so that reduces the chances of forming a tumor I think.

 

Pulsatile tinnitus often has a vascular origin. For example, many women get it when they are pregnant because of the hemodynamic changes of pregnancy but it resolves after birth.

Anyone with pulsatile tinnitus should get a full work up if you haven't already. At the very minimum check your blood pressure during these storms and compare it to your baseline.

 

Recently I've done a lot of digging on FX-322 discussions - especially on Facebook - just to see what people are saying about FX-322. I found one comment from someone saying their ENT told them that FX-322 had caused cancer in mice. I combed the net for more info but couldn't find anything, so I think their ENT may have been mistaken.

Whatever the case, Frequency Therapeutics wouldn't be putting so much money behind it if they thought it was going to cause people to get tumors. Also, I can't remember if I read it in this thread or not, but one of the ways they test these drugs for long term effects is to give large doses to mice and see how it affects their lifespan. If there's negative effects, they'll know the drug will possibly have negative effects for humans. So I kind of doubt the veracity of the Facebook comment I read (and it just goes to show that you can't trust random Facebook comments).

 

Carl LeBel specifically said that their studies did not show excessive cell/tissue proliferation. Maybe their ENT is confused?

 

I'm pretty sure that one of the advantages of their treatment is actually that PCA is inherently much safer than stem cells. FX-322 only temporarily activates the progenitor cells needed for FX-322 to do its work and restore hearing. Key word is temporary and you're just giving the cells the cue to switch on so it's very much about instigating a natural process. You also don't have the challenge of delivering and integrating the cells into their proper location, according to their website.

 

This just sounds like a classic knee-jerk reaction of 'don't be silly there'll NEVER be a treatment for hearing loss'. The ENT I mean.

 

I actually thought that I understood what you were saying, however I am thinking we may have different thoughts as to whether your specific trouble can be resolved. Right now tinnitus is known to take ten or so different forms in terms of sensations and sound. Since supposedly the source of the tinnitus you are experiencing is a lack of auditory stimulation, I really reckon that the same theory I posted before would also apply.

 

I think that there are two problems with reading what people have put anecdotally online.

Firstly, there's the terrible ability for people to post stuff that is negative and/or false and may put concerns in someone's mind without wanting or needing to support their claims. This will mean that people can say things for reasons like just wanting to get a response out of others or because they want to just post problematic misinformation. The amount of times that this has happened with COVID-19 related stuff is ridiculous and has hugely fuelled some of the problems. Just look at the people taking the unproven and ridiculous treatments that some imbecile has suggested.

Secondly, somebody could be posting patently false comments about FX-322 (or any other medicine for that matter) for the simple reason that they think that it is a total threat to them (most likely from a money and business perspective too). The trouble is in the day and age of the internet, it is very easy for people to willfully make negative comments about anything and have a detrimental effect on the service, product, firm etc.

Essentially we already see this regularly with examples like restaurant reviews which have been written by a competitor, which are both false and negative. Somebody says they found maggots in their meal and this turns people off going, because eating the food is viewed as a health risk. Thus making comments like a rat got cancer from FX-322 is detrimental in the same way that the maggots in food reports are. This is because it demonstrates that there possibly is a very adverse health outcome from having the treatment and thus people will avoid it. Then this benefits the companies providing the current treatment (hearing aids) because people will use those because they are a lot less risky.

I hope we won't see resistance from those who fall within the status quo such as audiologists. However I, unfortunately, feel that there are going to be some attempts at smearing restorative medicine like FX-322 and others from those that will lose. Look at the weak and also false claims made by a certain company to support their position that hearing aids need to be solely provided by certified audiologists (claims which were ultimately refuted and ultimately shown to be really ridiculous) when the OTC Hearing Aid law was being discussed. Also look at all their attempts to petition the law makers to change their stance and refuse to support the bill solely because it was going to dent their operation. Those making negative claims may benefit in the short-term until these claims get refuted and confidence in an item such as FX-322 is restored.

The difference between these questionable and also false claims being made in a public and fairly open discussion like parliament and being made online is that the person or organisation making false public comments can be taken to task by anyone and also directly if it is done publicly. Therefore making false claims online means that there is no known source to take to ask. Thus it is more challenging to refute these claims because firms like Frequency Therapeutics can't go to the source of the false claim(s), break it down piece by piece and ultimately expose the party making them.

Unfortunately, it is fairly probable that once again there will be people pushing the spreading of false information with FX-322 (and also all other restorative medicine), as it is unfortunately an effective, long standing and regularly used tactic across all areas to put doubt in people's mind about something to stop them taking up the new option.

Furthermore, we already have evidence of groups willing to spread false and/or largely meritless information in the hearing area. While ultimately these dodgy and false claims will end up being refuted due to them not stacking up when dissected, it is still going to do damage in the short-term. Unfortunately this means firms will need to invest time and resources refuting these false claims.

 

Ok cool. Is it likely that the root cause of tinnitus is high frequency hearing loss? What evidence do we have to indicate that?

 

@100Hz and @serendipity1996,

All this discussion about the middle ear is resonating with me too. And I agree that tinny speakers are the worst, my eardrums wince like hearing nails on chalkboard. My TV is unlistenable now without speakers.

I wake up and my ears wont be too bad, but by the end of the day tinnitus will be screaming and I'll have the burning, stuffy feeling in the canal and a muffled voice. Just like day 1. I feel like my ears are definitely caught in this "vicious cycle" where the muscle is forever overprotecting the sensitized frequencies.

This middle ear damage, if you want to call it that, is even more poorly understood and researched than cochlear damage. ENT told me my muscles were "oversensitized" but didn't offer any remedy. I didn't ask for one, only because I was totally sold on cochlear damage ahead of time. Now I'm wondering what his response would've been had I asked. Sorry you're fucked? Probably. Clonazepam it is.

I'm sure Liberman's right on about the cluster symptoms being initiated by even slight cochlear damage, but now I'm questioning how much the inner ear is responsible for the seemingly endless perpetuation of symptoms. Is it lingering neuroinflammation driving the physical symptoms? Can we treat the middle ear directly by any means, or is it futile to do so until the cochlear damage is addressed? The interrelation of inner and middle ear damage is a behemoth for someone to tackle.

There's gotta be a reset button on the ears somewhere.

 

I don't think that there is clear knowledge of what the cause of tinnitus is. It isn't able to be pinpointed, however reading what you said it seems possible that hearing loss is involved with it and hearing loss often is one of the main causes. The evidence to date does suggest as much because tinnitus is resolved in a very high number of cases when it is treated with options like either surgeries for conductive hearing loss or hearing aids for hair cell loss. Let's just say that I have heard of people with "no hearing loss" who have used a hearing aid without the masker and actually have had positive results.

It is true that there are other possible causes of tinnitus like TMJ, however based on what you have indicated I would be more inclined to try treating the hearing stuff first. From what I have been hearing and what I have been reading about, it seems hearing loss is a common cause of tinnitus. Even if your tinnitus was caused by another issue like TMJ the theory that not only professionals in the hearing field have but also those who work in the dentistry field feel that the jaw movement causes a temporary change in ear functionality. Thus this means a short term change in your hearing. Hence the temporary tinnitus.

 

Zero. FX-322 is simply two molecules turning on a switch to activate an otherwise natural process. This has occurred already with all of us when we were in the womb. If you believe Internet drama, look no further than Aspartame, the virtually harmless sweetener in Diet Coke for nearly 40 years and also known as Equal in the blue packets.

 

Nicely played.

 

I feel that we can expect to have these types of comments being made both during the trials and during the first stages after FX-322's release. I think that this will be the disinformation that we will potentially see from groups and individuals who are for one reason or another vehemently against regenerative medicine.

 

I believe the ‘cancer in mice story’ is the REGAIN drug orally/systemically. Different company, different delivery method, different drug.

 

So long as FX-322 when it's finally released isn't ridiculously expensive. I won't be very impressed if they decide to charge thousands of dollars per dose for the stuff, as I'd do just about anything within reason for a cure.

 

I think that they will charge comparatively to the cost of a hearing aid at this stage. It seems that this is the relevant comparative market. We might see FX-322 subsidised in some countries via government healthcare programs (eg: Australia) and insurance (eg: America). This will enable Frequency Therapeutics to obtain a better return if it is covered by government healthcare and also insurance.