Frequency Therapeutics — Hearing Loss Regeneration

[Piney]

Severe unilateral hearing loss with bad speech recognition. For a year with no hearing aid and just tinnitus. I was confused, forgot stuff in loud places and off balance even though I passed all the tests. The hearing aid makes wind and some noise sound like crap but the second I put it on I felt more grounded.

Synapses maybe bad but I swear it was all about getting sound in, cell replacement, cell growth, hearing aid whatever it takes. I swear it does something and I'm sure if this drug enhances anything it will be an improvement.

 

[ageoflove]

Probably they had no effect or very different effects? Would it be much faster if all participants got perfect hearing?

It's very exciting to know.

But in a phase 1 trial, wouldn't they see if there was some positive effect?

I think it's impossible to interpret anything or make conclusions right now. Everything is possible. Worst case is that nothing has improved and happened but they still try if there are any long time effects...

I remember I have read that the criteria to be participant of the trials are very regulated by the FDA. Don't take my word for granted but as far as I remember participants have to nearly fullfil the criteria of cochlear implant patients. So a lot of participants have probably very bad hearing (so they are not the mass of tinnitus patients with no or minimal measurable hearing loss). We also do not know how long the participants struggle with bad hearing (maybe decades...) and we don't know how much their auditory cortex has changed during this time.

So to say something optimistic: maybe they regained a lot of hair cells and synapses but it could be that it just takes more or fewer months until the brain can interpret those "new" signals again to finally hear crispy clear (and hopefully mute tinnitus)...

(((I don't know if you know about Dr. Josef Rauschecker's tinnitus model theory, but I'm pretty sure that tinnitus has always to do with (at least mini-minimal) hearing damages (which all people have since birth) and a filtering mechanism which at some point doesn't work for certain signals.)))

But that's only speculation from me...

Heads up girls and guys, we'll get the job done!

 

[Flamingo1]

Two years? Come on Frequency Therapeutics!

https://uk.news.yahoo.com/wonder-drugs-target-apos-zombie-190000268.html

 

[SergioN]

Hi All,

One concern I have about FX-322 and these types of of progenitor targeted drugs is that if the drug stimulates progenitor cells to create new ones and differentiate... And inner ear has progenitor cells... How does the drug "know" where the damage is? Maybe it stimulates zones that actually do not need repairing...

I have had tinnitus last 14 years but in January it spiked significantly and I did not manage correctly, so I finally took Paroxetine antidepressant, as I did when tinnitus appeared, but this time the result was pretty bad and tinnitus worsened a lot.

Although I took the minimum dose (10mg) during 6 days and then taper off.
This mistake has converted my life to hell so every day I enter this forum to see if there's any news about regeneration therapies.

Thanks to everyone on Tinnitus Talk for supporting the cause!

Regards.

 

[PeteJ]

Hi All,

One concern I have about FX-322 and these types of of progenitor targeted drugs is that if the drug stimulates progenitor cells to create new ones and differentiate... And inner ear has progenitor cells... How does the drug "know" where the damage is? Maybe it stimulates zones that actually do not need repairing...

I have had tinnitus last 14 years but in January it spiked significantly and I did not manage correctly, so I finally took Paroxetine antidepressant, as I did when tinnitus appeared, but this time the result was pretty bad and tinnitus worsened a lot.

Although I took the minimum dose (10mg) during 6 days and then taper off.
This mistake has converted my life to hell so every day I enter this forum to see if there's any news about regeneration therapies.

Thanks to everyone on Tinnitus Talk for supporting the cause!

Regards.

I recall that the researchers said, when they studied it in other animals in which it works inherently, the gene/DNA targets the damaged cells. That is what interested them. That's why they say their only role is to get the gene cocktail to the area and then let 'it' do all the work.

In other words, deliver the treatment safely and it should 'locate' the damaged hair cells/nerves.

Edit: I should add, so it makes more sense: the researchers say we have the regeneration ability but for some reason, it's 'turned off' in humans. So, the drug's role is to turn it on.

 

[Gorbeh3]

https://www.businesswire.com/news/h...utics-Announces-Appointment-Glenn-Dubin-Board

Asset management hotshot, net worth of $2.0 billion, I'd like to interpret this as good news.

https://en.wikipedia.org/wiki/Glenn_Dubin

 

[JohnAdams]

For all we know, they saw amazing results and the hold up is with the FDA. They are notorious for dragging their asses.

Considering the 3M earplug scandal that's happening and the unmet need of all the veterans which we allegedly support so much for defending our freedoms you'd think they would grant a special priority to this. Maybe it is and we just don't know yet. For all we know we could wake up one day soon and see news that they are releasing this as an open phase trial. I don't know I'm just very optimistic.

 

[grate_biff]

For all we know, they saw amazing results and the hold up is with the FDA

So the FDA is involved even when they aren't yet at phase II?

 

[Daniel Lion]

For all we know, they saw amazing results and the hold up is with the FDA. They are notorious for dragging their asses.

Dig the optimism captain, you the man.

 

[JohnAdams]

So the FDA is involved even when they aren't yet at phase II?

Yeah, when we speak of phases we are talking about FDA clinical trial phases. I, II, and III and their subdivisions.

 

[Aleksa Uzunovic]

Do you think that when the Frequency Therapeutics releases their drug that everyone will have to go to the US to get a treatment? Or will they sell the drug to the private clinics across the globe so that people can get treatment in their regions?

 

[JohnAdams]

Do you think that when the Frequency Therapeutics releases their drug that everyone will have to go to the US to get a treatment? Or will they sell the drug to the private clinics across the globe so that people can get treatment in their regions?

I think they will sell it internationally but they will more than likely have to go through the respective countries' approval processes first.

 

[Aleksa Uzunovic]

As for me, I personally believe more in the European Audion, as in Europe the system is somewhat more effective and faster than in the US. Audion is ushering into phase 2 as we speak. But I don't know whether the approach of Audion is potentially as effective as Frequency Therapeutics's?

 

[JohnAdams]

But I don't know whether the approach of Audion is potentially as effective as Frequency Therapeutics's?

I'm pretty sure they both work on the premise of cellular signaling pathways.

Someone correct me if I'm wrong but I think fundamentally it works like this:

Cell proliferation in LGR5+ stem cells is activated by Beta-Catenin entering into the nucleus.

White at top is outside the cell, grey thing between white and blue is the cellular membrane and the blue is inside the cell and the brown circle at the bottom is the nucleus.

Look in the left panel, there is something called the B-catenin destruction complex which destroys the B-catenin before it can enter into the nucleus. When certain cell signaling pathways are either activated or inhibited, it causes the B-catenin destruction complex to shut down which allows the B-catenin to enter into the nucleus which then triggers your DNA to begin the proliferation process and that is what is happening in the right panel. In this diagram, WNT activation is the process that is ceasing the B-catenin destruction complex.

There are foods that are WNT activators. Before I tried my curcumin experiment, I tried to eat a bunch of carrageenan, a food additive that also triggers WNT activation. I ate so much that my heart rate slowed and I got dizzy and thought I was going to die.

Common food additive carrageenan stimulates Wnt/ β-catenin signaling in colonic epithelium by inhibition of nucleoredoxin reduction.
https://www.ncbi.nlm.nih.gov/pubmed/24328990

Carrageenan is a seaweed extract thats in everything. They use it to thicken sauces like ketchup and other things like toothpaste.

All of this leads me to believe that there is some kind of way to just eat something or a combination of things that will cure our hearing loss. When they were testing ly411575 initially, they administered it orally to the rodents and it restored their hearing but also changed their skin color, made their hair fall out and gave them skin tumors.

 

[TeslaGuy]

As for me, I personally believe more in the European Audion, as in Europe the system is somewhat more effective and faster than in the US. Audion is ushering into phase 2 as we speak. But I don't know whether the approach of Audion is potentially as effective as Frequency Therapeutics's?

As an European myself I don't believe there will be one universal treatment and that is good thing that every company is not trying the exactly same method. I don't care who provides the treatment as long as it is safe and effective but I agree as well that European system is somewhat faster and more reasonable.

 

[Coleoptere]

There is a Mutual Recognition Agreement (MRA) between Europe and the USA that makes possible that approved medicines are valid in both sides of the Atlantic

https://www.fda.gov/internationalprograms/agreements/ucm598735.htm

Maybe Frequency Therapeutics (and we) were better of if they had started their trial over here in Europe.

 

[JohnAdams]

There is a Mutual Recognition Agreement (MRA) between Europe and the USA that makes possible that approved medicines are valid in both sides of the Atlantic

https://www.fda.gov/internationalprograms/agreements/ucm598735.htm

Maybe Frequency Therapeutics (and we) were better of if they had started their trial over here in Europe.

Well Europe has Audion. That's good so they don't have all their irons in one fire.

 

[JohnAdams]

@PolishSoldier87

What's up man? You doing alright?

 

[ageoflove]

As for me, I personally believe more in the European Audion, as in Europe the system is somewhat more effective and faster than in the US. Audion is ushering into phase 2 as we speak. But I don't know whether the approach of Audion is potentially as effective as Frequency Therapeutics's?

It's hard to say who is going to be the first with relevant success rates.

Companies from the US are often "making more noise" during the developments.

European companies are often more unremarkable, but sometimes hit the market with a big bang.

Doesn't matter who is the first.
In the end we'll hopefully and probably have a few different products on the counter!

 

[andreimatei]

I've been following this thread for a long time and it's very exciting. I feel hopeful.

My question is: have there been past attempts at something similar to this with as much excitement, press, positive talk tracks from the company and promise around it that then fell flat at some stage of the trials or are we really looking at something that truly seems like a first? Less about the mechanism of the medicine and more around the buzz around it and how much that buzz should be an indicator of future success...

In other words, have we been down a road like this before only to be disappointed after getting super fired up or have past things not had as much positive talk from both the company and industry media coverage?

I'm trying to gauge if we all should be as excited as we are because we're truly seeing something different than in the past...

I truly want to continue being excited about this so please don't take this question as me being a downer on it!

Grateful for all opinions.

 

[swc5150]

The Autifony trial had every super excited, then failed. But, that trial was based on a theory/assumption that needed to be tested, without hard evidence of anything. Obviously the same can be said here, but Frequency already proved they can generate new hair cells. I'm way over-simplifying, but I think there's more reason for optimism with this.

 

[RB2014]

I've been following this thread for a long time and it's very exciting. I feel hopeful.

My question is: have there been past attempts at something similar to this with as much excitement, press, positive talk tracks from the company and promise around it that then fell flat at some stage of the trials or are we really looking at something that truly seems like a first? Less about the mechanism of the medicine and more around the buzz around it and how much that buzz should be an indicator of future success...

In other words, have we been down a road like this before only to be disappointed after getting super fired up or have past things not had as much positive talk from both the company and industry media coverage?

I'm trying to gauge if we all should be as excited as we are because we're truly seeing something different than in the past...

I truly want to continue being excited about this so please don't take this question as me being a downer on it!

Grateful for all opinions.

We have been down this road before with CGF-166. This however, seems more promising. You should be cautiously optimistic that this will work. We still don't know how well it will work though and for whom it will work. There are still many unanswered questions.

 

[jeff W]

...our biggest hope to get FX-322 on the market soon is that the regeneration of OHC's and IHC's really works (in a functional way and on the right spots) and on the other hand that our brains' neuroplasticity takes place fast enough and in the right way.

What still seems to be very unknown is if the damaged synapses (hidden hearing loss) can grow (or rewire) in the right way...

...on top of that we have to see if our brains' (auditory cortex) are able to detect and interpret those new (or old...) signals in a (the) way which nature had determined.

Time is not relevant, information is everything, the signal is god, restore the signal & reverse the disorder.

See at 11:42.

 

[jeff W]

I wonder if it's really only the known noise, TMJ, TMD, head/neck, muscle, blood vessel stuff which causes tinnitus. Maybe we are already living in the "age of neurological diseases", with unknown viruses, inflammations, and stuff are responsible for the higher and higher number of tinnitus sufferers.

Ever noticed the amount of northern Europeans/Nordics on these forums and indeed on the Facebook ones. There are distinct sets of genes that are common in certain ear disorders, see the work of Jose Antonio Lopez-Escamez. Fair hair and blue eyes seem to greatly increase the chance you will have a maladaptive/erroneous immune response to simple ear pathogens/damage.

 

[PeteJ]

It's not a 'one size fits all deal' though, right?

But, they think that the studies on mice are applicable to humans and the one common denominator for all of us is hearing loss. Abrupt hearing loss, perhaps? Whether it shows up on an audiogram or not, it is still about damage and how it contributes to tinnitus and other problems so it should work in theory? :-/

I will reiterate, I hope scientists and researchers can figure it all out. Would be good if they could heal nerves, synapses and view the cochlear nucleus somehow, though.

 

[TeslaGuy]

@JohnAdams
Are Audion and Frequency Therapeutics the first to try signaling pathways or has there been already someone else?

 

[Aleksa Uzunovic]

There is a cure folks, hair cells can be restored in humans. We got them restored in mice and some other mammals and in vitro in humans. The only thing is that because these companies are bunch of inefficient pric** it's not available in the clinics for us. I just hope that Audion which is so much more efficient takes the entire market (and thus money) from Frequency Therapeutics and beats it to the punch for being such a bunch of freaking slow ass**les.

 

[ageoflove]

There is a cure folks, hair cells can be restored in humans. We got them restored in mice and some other mammals and in vitro in humans. The only thing is that because these companies are bunch of inefficient pric** it's not available in the clinics for us. I just hope that Audion which is so much more efficient takes the entire market (and thus money) from Frequency Therapeutics and beats it to the punch for being such a bunch of freaking slow ass**les.

I'm also convinced that regeneration of periphery is possible. The big question is if and how regenerated periphery works...

It's true that progress seems to be very slow but on the other hand we have to understand that all the procedures must be safe. If Frequency Therapeutics would cause a lot of damage or trouble in their test persons because they hurry, it could be that FDA stops their developments, even if it's only one more step and a few corrections to make.

 

[ageoflove]

It's not a 'one size fits all deal' though, right?

But, they think that the studies on mice are applicable to humans and the one common denominator for all of us is hearing loss. Abrupt hearing loss, perhaps? Whether it shows up on an audiogram or not, it is still about damage and how it contributes to tinnitus and other problems so it should work in theory? :-/

I will reiterate, I hope scientists and researchers can figure it all out. Would be good if they could heal nerves, synapses and view the cochlear nucleus somehow, though.

I must say again that Dr. Josef Rauschecker's Theory of Tinnitus is the most plausible one to me.

I think loud tinnitus (not talking about tinnitus that you can only hear if you concentrate very hard when it's silent) has always to do with - at least minimally - damage to hearing periphery. Hearing Periphery (from the outer ear to the brain) cannot regenerate naturally. Since I think everyone gets hearing damage through lifetime (yes if you are over 30 years old you definitely won't hear 18, 17, 16 kHz on low dB levels).

Nature gave our brains filter mechanisms which can handle damages to a certain level. In certain cases or conditions (science will maybe tell us exactly one day) our filters fail and we hear tinnitus.

So in my opinion there are at least 3 ways to stop tinnitus.

-restore hearing damage
-stop the tinnitus signal (synchronized hyperactive nerve signals)
-repair or improve the brain's filter

I think at the moment there's a race going on who (and which method) will be be the first with a significant success rate!

 

[PeteJ]

I must say again that Dr. Josef Rauschecker's Theory of Tinnitus is the most plausible one to me.

I think loud tinnitus (not talking about tinnitus that you can only hear if you concentrate very hard when it's silent) has always to do with - at least minimally - damage to hearing periphery. Hearing Periphery (from the outer ear to the brain) cannot regenerate naturally. Since I think everyone gets hearing damage through lifetime (yes if you are over 30 years old you definitely won't hear 18, 17, 16 kHz on low dB levels).

Nature gave our brains filter mechanisms which can handle damages to a certain level. In certain cases or conditions (science will maybe tell us exactly one day) our filters fail and we hear tinnitus.

So in my opinion there are at least 3 ways to stop tinnitus.

-restore hearing damage
-stop the tinnitus signal (synchronized hyperactive nerve signals)
-repair or improve the brain's filter

I think at the moment there's a race going on who (and which method) will be be the first with a significant success rate!

Do you think there is any hope at all of science/scientists figuring out how to do all three any time soon and having an effective treatment on human sufferers?

I have ear pain as well as tinnitus. I am told that's hyperacusis. I am told that it's related to the jaw, TMJ-like. I never had these problems before. I don't know if I can wait for a cure but I hope for all of our sake that they discover how to heal/cure these problems sooner rather than later.