Frequency Therapeutics — Hearing Loss Regeneration

[MrCrybaby]

I really want FX-322 to work, but I wonder if we are all getting our hopes up too high. I don't want to be pessimistic or a killjoy, but what if it either doesn't get through the trials or on to the market or is shown to be not that effective? I feel many of us, me included, would be in for a massive anti climax.

Anybody else have these thoughts?

I suspect that FX-322 will have great benefits for many people. However it is important to be aware that the only sure fire solution is full restoration of the auditory system. Many hearing disorders, and the ear as a whole, are poorly understood by science at this time.

What really matters about FX-322 in my eyes is that it has the potential to completely shift the expectations of patients to demand more from research than mindfulness, yoga, CBT, and other coping mechanisms that do not impact symptoms. When regenerative medicine is in the public consciousness it could change everything, not just for tinnitus but all chronic diseases.

 

[FGG]

I really want FX-322 to work, but I wonder if we are all getting our hopes up too high. I don't want to be pessimistic or a killjoy, but what if it either doesn't get through the trials or on to the market or is shown to be not that effective? I feel many of us, me included, would be in for a massive anti climax.

Anybody else have these thoughts?

I personally would be way more pessimistic if it didn't double word scores with a safety dose. The drug clearly works. The only way I could see it not being released is if the larger dose is more systemically absorbed but based on the pharmacokinetics of the first study, that seems pretty unlikely to be a problem.

I think if your tinnitus is from cochlear damage and you have any LGR+ cells left (i.e. you don't have profound hearing loss), this drug should help unless you have just synapse damage, in which case you'd need a synaptopathy drug.

 

[all to gain]

I personally would be way more pessimistic if it didn't double word scores with a safety dose. The drug clearly works. The only way I could see it not being released is if the larger dose is more systemically absorbed but based on the pharmacokinetics of the first study, that seems pretty unlikely to be a problem.

I think if your tinnitus is from cochlear damage and you have any LGR+ cells left (i.e. you don't have profound hearing loss), this drug should help unless you have just synapse damage, in which case you'd need a synaptopathy drug.

You make me feel more optimistic. Just wish I definitely 'knew' what damage I have. If I have auditory nerve damage I feel like I am out of luck.

 

[Momme]

@FGG

Do I have IHC damage? If yes, will FX-322 help me?

 

[Lucifer]

I thought they finished the trial on time (January) and the "delay" is just that they haven't released results yet. I'm not sure what the normal time frame between trial completion and the release of results usually is so I am not sure if this constitutes a "delay" or not.

From Audion's website:

"Recruitment of patients for phase 2 commenced in January 2019 in Tübingen, Athens and London and recruitment has now been concluded, study finalised and data being analysed."

That could be the reason for the delay but originally it was estimated to have results come out by end of January. Maybe the trials were longer than expected so they changed it to end of April to review the results.

 

[FGG]

@FGG

Do I have IHC damage? If yes, will FX-322 help me?

You have asked me that before and my answer is the same: no one can tell you that. Audiograms only can tell you if you have OHC damage and you do. FX-322 should address both, however, at the frequencies you appear to have issue with based on your audiogram.

 

[FGG]

You make me feel more optimistic. Just wish I definitely 'knew' what damage I have. If I have auditory nerve damage I feel like I am out of luck.

No doubt about it, we need better testing.

 

[Lucifer]

@FGG

I looked at the clinical trials and the estimated participation is 96 but I don't think that has changed since they added the 4 new locations. I assume it would be more now with the additional 4 new locations.

 

[FGG]

@FGG

I looked at the clinical trials and the estimated participation is 96 but I don't think that has changed since they added the 4 new locations. I assume it would be more now with the additional 4 new locations.

I'm not sure if that's a change or not, honestly. But yes I would assume if that was the original number, they would have to change the estimate on the page at some point to reflect an increase.

 

[Diesel]

I'm not sure if that's a change or not, honestly. But yes I would assume if that was the original number, they would have to change the estimate on the page at some point to reflect an increase.

96 is the original target for the Phase 2A. As far as I can tell, there is no requirement to change an estimated number. So, the could very well expand the locations and get 90 participants, or 150; hence why it is an estimate.

 

[Lucifer]

96 is the original target for the Phase 2A. As far as I can tell, there is no requirement to change an estimated number. So, the could very well expand the locations and get 90 participants, or 150; hence why it is an estimate.

Yes I thought so. The more participants in the clinical trials will hopefully allow FX-322 to achieve breakthrough therapy status.

 

[Tweedleman]

However it is important to be aware that the only sure fire solution is full restoration of the auditory system. Many hearing disorders, and the ear as a whole, are poorly understood by science at this time.

This is my worry. Even in the Frequency Therapeutics video they mention how "elegantly complex" the hearing system is. Considering how relatively recent cochlear synaptopothy was discovered, my big concern is, have we accounted for everything that can break down leading to hearing loss/tinnitus? For arguments sake let's assume FX-322 can completely regenerate all hair cells and the synaptopothy drugs can repair all synapses. Would that be enough to restore the cochlea, at least in the more generic noise-induced/ototoxic cases?

 

[Lucifer]

This is my worry. Even in the Frequency Therapeutics video they mention how "elegantly complex" the hearing system is. Considering how relatively recent cochlear synaptopothy was discovered, my big concern is, have we accounted for everything that can break down leading to hearing loss/tinnitus? For arguments sake let's assume FX-322 can completely regenerate all hair cells and the synaptopothy drugs can repair all synapses. Would that be enough to restore the cochlea, at least in the more generic noise-induced/ototoxic cases?

It's hard to tell but I know for certain when it comes out in the US if people mentioning about improving their tinnitus and hyperacusis (loudness and pain) then I'm definitely trying it out.

 

[MrCrybaby]

This is my worry. Even in the Frequency Therapeutics video they mention how "elegantly complex" the hearing system is. Considering how relatively recent cochlear synaptopothy was discovered, my big concern is, have we accounted for everything that can break down leading to hearing loss/tinnitus? For arguments sake let's assume FX-322 can completely regenerate all hair cells and the synaptopothy drugs can repair all synapses. Would that be enough to restore the cochlea, at least in the more generic noise-induced/ototoxic cases?

I think people with a complaint of only tinnitus or only speech in noise have a very good shot at returning to "normal". It's when you enter the realm of even less understood ear disorders it's harder to predict.

How can we say these medicines will fix TTTS and middle ear twitching, noise induced pain in the ears, face and neck, or strange sound distortions when we don't understand what causes them?

Don't be discouraged though! Repairing some of the damage is better than repairing none of the damage. FX-322 is not the final destination.

As we improve our understanding (thanks to Charles Lieberman for his groundbreaking research) we will be better able to know what is wrong and how to fix it.

Look at it this way: the discovery of insulin didn't cure diabetes but it certainly kicked things off!

 

[FGG]

This is my worry. Even in the Frequency Therapeutics video they mention how "elegantly complex" the hearing system is. Considering how relatively recent cochlear synaptopothy was discovered, my big concern is, have we accounted for everything that can break down leading to hearing loss/tinnitus? For arguments sake let's assume FX-322 can completely regenerate all hair cells and the synaptopothy drugs can repair all synapses. Would that be enough to restore the cochlea, at least in the more generic noise-induced/ototoxic cases?

I think noise-induced folks will for sure be helped. These drugs are primarily tested on noise induced humans and show good results so far based on what we know.

As far as ototoxicity, I choose to remain optimistic based on the fact that a lot of the preclinical work was done with ototoxins (aminoglycosides anyway) and I think it would have come out at that time that certain cells/structures were too damaged to enable regeneration after and, if that was the case, they wouldn't use ototoxins to incite damage to test these drugs.

 

[Lucifer]

I think people with a complaint of only tinnitus or only speech in noise have a very good shot at returning to "normal". It's when you enter the realm of even less understood ear disorders it's harder to predict.

How can we say these medicines will fix TTTS and middle ear twitching, noise induced pain in the ears, face and neck, or strange sound distortions when we don't understand what causes them?

Don't be discouraged though! Repairing some of the damage is better than repairing none of the damage. FX-322 is not the final destination.

As we improve our understanding (thanks to Charles Lieberman for his groundbreaking research) we will be better able to know what is wrong and how to fix it.

Look at it this way: the discovery of insulin didn't cure diabetes but it certainly kicked things off!

I do think FX-322 will help with the majority of us who have damaged hair cells due to acoustic trauma which should fix our tinnitus, hyperacusis (loudness and pain) and hearing loss.

I think we will see FX-322 within 1-2 years if they can get the breakthrough therapy status which happens most likely.

 

[serendipity1996]

Pretty sure this article was posted a few pages back, an up-to-date analysis of the different companies who are conducting clinical trials on inner ear regeneration. Unfortunately it's behind a paywall, was anyone able to access the full text?

https://www.biocentury.com/article/304491

 

[ajc]

Pretty sure this article was posted a few pages back, an up-to-date analysis of the different companies who are conducting clinical trials on inner ear regeneration. Unfortunately it's behind a paywall, was anyone able to access the full text?

https://www.biocentury.com/article/304491

It's only $85o with a license to publish on one website. Buy it and share here.

 

[Jaysterk]

All markets are down substantially over the past week; Frequency Therapeutics isn't immune to market volatility.

I can second this.

 

[Jaysterk]

It's only $85o with a license to publish on one website. Buy it and share here.

I'm down to pitch in.

 

[FGG]

We should buy this one too:

https://journals.lww.com/otology-ne...ection,_Restoration,_and_Regeneration_.2.aspx

It mentions 43 different companies working on restoration, many of who will enter the field within the "next few years."

 

[annV]

We should buy this one too:

https://journals.lww.com/otology-ne...ection,_Restoration,_and_Regeneration_.2.aspx

It mentions 43 different companies working on restoration, many of who will enter the field within the "next few years."

I have it for you...

 

[MrCrybaby]

I do think FX-322 will help with the majority of us who have damaged hair cells due to acoustic trauma which should fix our tinnitus, hyperacusis (loudness and pain) and hearing loss.

I think we will see FX-322 within 1-2 years if they can get the breakthrough therapy status which happens most likely.

Regenerating hair cells will definitely benefit all persons with damaged hair cells. If your only problems are ringing, hearing loss, and hyperacusis from recruitment things are looking pretty great!

I just have no way of knowing if it will help with ear pain, facial/neck pain, or middle ear muscle twitches (plus other edge case symptoms) because no one understands what make them happen in the first place.

With all of this in mind, I still pumped FX-322!! It will help lots of people, I suspect even those that it doesn't fully cure.

 

[FGG]

I have it for you...

You always seem to be able to get info no one else can .

 

[Tweedleman]

"There will be no single cure for hearing, tinnitus or balance impairments, and so clinicians will play a key role in advising patients which therapy to choose. Clinicians involved in the care of these patients need to prepare for what may lead to significant changes to hearing care and services. Developing knowledge of these therapies and their mechanisms of action is vital and will require dedicated education and training for both the current and future generations of clinicians."

The audiologists and ENTs wont know what hit them.

 

[Lucifer]

Regenerating hair cells will definitely benefit all persons with damaged hair cells. If your only problems are ringing, hearing loss, and hyperacusis from recruitment things are looking pretty great!

I just have no way of knowing if it will help with ear pain, facial/neck pain, or middle ear muscle twitches (plus other edge case symptoms) because no one understands what make them happen in the first place.

With all of this in mind, I still pumped FX-322!! It will help lots of people, I suspect even those that it doesn't fully cure.

Hyperacusis (ear pain) is my main issue. I really hope it does work.

 

[FGG]

Trying to go through the link one by one but this was interesting from Sound Pharmaceuticals website concerning a "cyclin dependent kinase inhibitor 1B (p27Kip1)" that they have in pre-clinical for *profound* loss:

"Importantly, these newly dividing cells have the capacity to become replacement auditory hair cells, supporting cells, and neurons in adulthood (Osterle et al 2011)."

Hopefully it has the same effects on human cells!

 

[Serouj]

Regenerating hair cells will definitely benefit all persons with damaged hair cells. If your only problems are ringing, hearing loss, and hyperacusis from recruitment things are looking pretty great!

I just have no way of knowing if it will help with ear pain, facial/neck pain, or middle ear muscle twitches (plus other edge case symptoms) because no one understands what make them happen in the first place.

With all of this in mind, I still pumped FX-322!! It will help lots of people, I suspect even those that it doesn't fully cure.

Ear & neck pain? What did the doctors tell you?

 

[Sevv]

Regenerating hair cells will definitely benefit all persons with damaged hair cells. If your only problems are ringing, hearing loss, and hyperacusis from recruitment things are looking pretty great!

I just have no way of knowing if it will help with ear pain, facial/neck pain, or middle ear muscle twitches (plus other edge case symptoms) because no one understands what make them happen in the first place.

With all of this in mind, I still pumped FX-322!! It will help lots of people, I suspect even those that it doesn't fully cure.

I sometimes speculate that people with visual snow or unexplained pain might have a reduction in VS when hearing loss is adressed because it might correct the thalamocortical dysrhythmia (TCD) that is caused by tinnitus, thus allowing the brain to filter out again VS/pain (TCD is speculated to be a symptom of fibromyalgia for example).

Think of it like: tinnitus represents 10 points of TCD, and VS 5. The brain can filter 7 points of TCD and after that, you get symptoms (so in this example a bit of tinnitus and VS). If tinnitus vanishes due to healing the ear, maybe the brain can filter out VS once again.
The filter is probably vastly different for people. An acquaintance of mine had sudden sensorineural hearing loss and hears pretty badly on one ear, but does not have tinnitus (has difficulty with pressure equalization now though). Another acquaintance on the other hand got quite the ringing (but is fully habituated...).

Pure speculation, but it is my hope because it would be my first chance to get rid of VS.

Regeneration might even help people who have unknown cause for tinnitus, because hearing loss might still be a small part of the underlying cause so at least you can get a reduction.

 

[MrCrybaby]

Ear & neck pain? What did the doctors tell you?

Facial/head/neck pain radiating from the ear is a symptom of hyperacusis. Hyperacusis, at this stage, is sort of just a cluster of symptoms that science doesn't understand the mechanisms of.