Frequency Therapeutics — Hearing Loss Regeneration

[HootOwl]

We all had great working channels but life stress ran down the battery voltage and we can no longer use the push to start button...

That's not how voltage gating works...

 

[Christiaan]

Ah, I see what you mean about the first possibility. But aren't the ion channels present at birth? I have to admit I'm a bit confused by his explanation in them not forming after acoustic trauma. Perhaps I'll email him asking for clarification.

Way ahead of ya I've already sent an e-mail to the Dr.

It is indeed confusing. It is likely the case that for most of us, we have normal functioning ion channels at birth. The thing is that acoustic trauma may have a devastating impact on the workings of these channels (sigh, another ear thing that is susceptible to damage, what else?). If Dr. Tzounopoulos' statement is true, than this would be quite a bummer to say the least

 

[dan]

Way ahead of ya I've already sent an e-mail to the Dr.

It is indeed confusing. It is likely the case that for most of us, we have normal functioning ion channels at birth. The thing is that acoustic trauma may have a devastating impact on the workings of these channels (sigh, another ear thing that is susceptible to damage, what else?). If Dr. Tzounopoulos' statement is true, than this would be quite a bummer to say the least

So he doesn't know shit. He just read Trobalt helped some people here, and made it "15x more potent"... the rest is a Hail Mary.

 

[dan]

That's not how voltage gating works...

I never said that's how they work.
What I meant that stress weakens their function, and you can't deny that...

Frequent Tinnitus Talk quotes:
"When I'm stressed out, my tinnitus goes thru the roof"
"My tinnitus quiets after taking a bath"

 

[mrbrightside614]

We all had great working channels but life stress ran down the battery voltage and we can no longer use the push to start button... we need to use the kickstarter to fire it back to life.
Notice how so many people here say that tinnitus began after a period of stress/anxiety/depression/loss of loved one, etc. Seems these channels are very sensitive to our mental state.

Regeneration should help a lot because there will be less need for the "brakes"...
The brain will regain some input from the cochlea and that would reduce hyperactivity directly. The amount of regained input will be directly proportional with tinnitus reduction.
Ideally zero hearing loss=zero tinnitus.
That's why nature created gating mechanism to compensate for lack of input. Kind of inefficient system, would be much simpler to evolve an auditory cortex that only has input and no "output".

Those with severe tinnitus may end up with mild/moderate tinnitus, which would be a cake walk after this daily torture...

I actually think the key thing here is level of actual hearing damage. People with severe tinnitus and moderate to minimal hearing loss, I think, could result in the near or complete tinnitus remission probably experienced by mild sufferers.

 

[dan]

So basically, you're screwed if:

1. You have flat epithelial...

2. Your Kv channels are fried...

Tinnitus just keeps screwing you up the ass.

 

[dan]

I actually think the key thing here is level of actual hearing damage. People with severe tinnitus and moderate to minimal hearing loss, I think, could result in the near or complete tinnitus remission probably experienced by mild sufferers.

So.

Degree of hearing loss = degree hair cell damage.
Degree of tinnitus = degree of damaged Kv.

 

[HootOwl]

I never said that's how they work.
What I meant that stress weakens their function, and you can't deny that...

Frequent Tinnitus Talk quotes:
"When I'm stressed out, my tinnitus goes thru the roof"
"My tinnitus quiets after taking a bath"

You mentioned some strange connection between stress and the "batteries" of voltage gating...

The mechanisms involved with stress and tinnitus is also still under investigation (and can get complex) but most of the research involves GABA, other neurotransmitters, or the limbic system as a whole.

Therefore, it's a substantial stretch imo to claim that stress somehow weakens the potassium ion channels. I haven't seen anything in the current literature to suggest that, but if you've come across that I would be interested to read about it. Not saying it's not possible, but I'd need to see some data before concluding that to be the case.

 

[FGG]

So basically, you're screwed if:

1. You have flat epithelial...

2. Your Kv channels are fried...

Tinnitus just keeps screwing you up the ass.

What he said about the condition of the channels wasn't at all clear to me.

It sounded like he said in general there are two options for channel problems but, in his studies, he found that the ones with noise induced were there but needed to be opened i.e.: not fried. Overall, his answers were among the most vague of the interviews I have seen here so it's a bit hard to interpret what he meant imo. If I had to guess he was talking more about theoretical reasons a channel might not work, it didn't sound like he observed any of that though.

Flat epithelia is much more likely to be a much bigger issue I think. It's hard to imagine waiting 15-20 years for a resolution to this.

 

[FGG]

I never said that's how they work.
What I meant that stress weakens their function, and you can't deny that...

Frequent Tinnitus Talk quotes:
"When I'm stressed out, my tinnitus goes thru the roof"
"My tinnitus quiets after taking a bath"

I think that has more to do with a Glutamate/GABA imbalance than the fusiform ion channels.

 

[dan]

in his studies, he found that the ones with noise induced were there but needed to be opened i.e.: not fried.

Ok goodie then, not fried, thank you FGG.

 

[ThomasC]

I'm confused. I read a few studies about flat cochlear epithelial, one says that it occurs when you have severe hearing loss (70 dB), not profound (90 dB). FX-322 trial includes subjects with mild to severe hearing loss, which means a pure tone audiometry within 26-70 dB.

It sucks for those who have severe hearing loss at the tinnitus frequency. Complete regeneration of the inner ear will take at least 10 years.

 

[AtlasFainted]

I'm confused. I read a few studies about flat cochlear epithelial, one says that it occurs when you have severe hearing loss (70 dB), not profound (90 dB). FX-322 trial includes subjects with mild to severe hearing loss, which means a pure tone audiometry within 26-70 dB.

It sucks for those who have severe hearing loss at the tinnitus frequency. Complete regeneration of the inner ear will take at least 10 years.

Doesn't flat epithelial mean there's nothing left at that frequency? If you have severe loss you can still perceive sound, even if barely so. Logic dictates that there still must be something in that area in order for sound to be perceived.

 

[FGG]

I'm confused. I read a few studies about flat cochlear epithelial, one says that it occurs when you have severe hearing loss (70 dB), not profound (90 dB). FX-322 trial includes subjects with mild to severe hearing loss, which means a pure tone audiometry within 26-70 dB.

It sucks for those who have severe hearing loss at the tinnitus frequency. Complete regeneration of the inner ear will take at least 10 years.

I believe it's possible starting at severe but is a guarantee by the time you are in the profound range.

 

[UKBloke]

I actually think the key thing here is level of actual hearing damage. People with severe tinnitus and moderate to minimal hearing loss, I think, could result in the near or complete tinnitus remission probably experienced by mild sufferers.

That would be nice.

 

[all to gain]

I actually think the key thing here is level of actual hearing damage. People with severe tinnitus and moderate to minimal hearing loss, I think, could result in the near or complete tinnitus remission probably experienced by mild sufferers.

I have mild hearing loss, but at 8000 Hz it is moderate, then above 9500 Hz I hear nothing (using online tests). Even if my hearing up until 9500 Hz is improved by FX-322, I will still have no hearing after that range. I presume then that I will still have tinnitus. That said, I'm not sure of the frequency of my tinnitus as I find it hard to match, so maybe I will get lucky if my tinnitus is lower than 9500 Hz?

 

[dan]

I think that has more to do with a Glutamate/GABA imbalance than the fusiform ion channels.

Oh yeah! Forgot about good ol' GABA.

I remember when I first got severe tinnitus back in 2011 GABA was the #1 hit.

Every pharma was looking for a tinnitus cure in GABA. Then that failed, we moved on to NDMA receptors or some crap, we had at one point Australian researchers trying Meth or LSD whatever... then that flopped and we started with KV channels... our first attempt was Autifony.

It's like we are playing Cold/Hot game blindfolded.
I hope we are getting hot this time...

 

[FGG]

Oh yeah! Forgot about good ol' GABA.

I remember when I first got severe tinnitus back in 2011 GABA was the #1 hit.

Every pharma was looking for a tinnitus cure in GABA. Then that failed, we moved on to NDMA receptors or some crap, we had at one point Australian researchers trying Meth or LSD whatever... then that flopped and we started with KV channels... our first attempt was Autifony.

It's like we are playing Cold/Hot game blindfolded.
I hope we are getting hot this time...

If there wasn't such a thing as receptor tolerance and down regulation, hitting GABA receptors hard would actually be an effective treatment.

I would be worried about the same thing with ion channels (though they don't behave like Neuro transmitter receptors) except that it doesn't seem to be the case that people need to stay on them indefinitely.

 

[mrbrightside614]

I hope you're right. @HootOwl. However, I've just read the transcript of the podcast with Tzounopoulos, and he mentioned that there are two possibilities that ion potassium channels may not work:

1) the ion channels are permanently damaged after acoustic trauma (RL-81 might not help)
2) the ion channels are present, but are not functioning properly (RL-81 might help)

So, considering the 1st possibility, it seems that there is a chance some of us have permanent damage to the ion channel?

Here's the quote about the 1st possibility:
''What is the problem, why do they not work? Again, there are two major ways that a channel can stop working. One is that these channels they have to synthesise inside the cell, and they have to go to the membrane of the neuron to allow for this in and out of the ions that I told you. It could be that the channels never make it to the membrane, they are not formed somehow after noise trauma and tinnitus. They are ruined for whatever reason.'' (p.8)

We have loads of anecdotal experiences to prove that ion channels are not completely devastated. I think it's awesome a researcher has taken notice and decided to use Trobalt as his blueprint. If Retigabine were still available today I would NO DOUBT take it as long as I needed to. I'm already on meds that have blackbox warnings due to my tinnitus, and this would more directly treat the problem.

 

[AtlasFainted]

I have mild hearing loss, but at 8000 Hz it is moderate, then above 9500 Hz I hear nothing (using online tests). Even if my hearing up until 9500 Hz is improved by FX-322, I will still have no hearing after that range. I presume then that I will still have tinnitus. That said, I'm not sure of the frequency of my tinnitus as I find it hard to match, so maybe I will get lucky if my tinnitus is lower than 9500 Hz?

A couple users on this thread have reported having a drop off in the higher frequencies where they seem to hear nothing during online tests. I have the same problem at 9kHz, in my right ear.

However upon getting an actual extended audiogram, they discover that they do still have some hearing at those frequencies.

This probably has to do with the special calibrated equipment that is used during an extended audiogram, and the fact that they crank up the volume all the way to 90dB if necessary.

I haven't gotten an extended audiogram yet but I plan to once FX-322 hits the market.

 

[dan]

@FGG

Could you ask Prof. Thanos Tzounopoulos if RL-81 has a better cardiac safety profile than Retigabine?

Trobalt has a bad effect on QT heart interval. Was he able to resolve that?
This is very important for me.

I think also Danny Boy's heart stopped due to Trobalt (although he was symptom free for a long while). He was like 20 years old and his heart just stopped afaik, and he died.

 

[all to gain]

A couple users on this thread have reported having a drop off in the higher frequencies where they seem to hear nothing during online tests. I have the same problem at 9kHz, in my right ear.

However upon getting an actual extended audiogram, they discover that they do still have some hearing at those frequencies.

This probably has to do with the special calibrated equipment that is used during an extended audiogram, and the fact that they crank up the volume all the way to 90dB if necessary.

I haven't gotten an extended audiogram yet but I plan to once FX-322 hits the market.

They crank it up to 90dB? Welcome new worse tinnitus tone...

Yeah, I made an earlier post about not being able to hear frequencies after 9500 Hz according to online tests. I'm sure I must have had hearing loss before I got tinnitus, but since having a neurotoxic/ototoxic reaction my hearing must have gotten worse and my brain seems to have picked up on it and voila tinnitus. I just hope my tinnitus is at a frequency that FX-322 can reach.

 

[ThomasC]

@FGG

Could you ask Prof. Thanos Tzounopoulos if RL-81 has a better cardiac safety profile than Retigabine?

Trobalt has a bad effect on QT heart interval. Was he able to resolve that?
This is very important for me.

I think also Danny Boy's heart stopped due to Trobalt (although he was symptom free for a long while). He was like 20 years old and his heart just stopped afaik, and he died.

You can send him an email. He often respond to his emails.

 

[FGG]

@FGG

Could you ask Prof. Thanos Tzounopoulos if RL-81 has a better cardiac safety profile than Retigabine?

Trobalt has a bad effect on QT heart interval. Was he able to resolve that?
This is very important for me.

I think also Danny Boy's heart stopped due to Trobalt (although he was symptom free for a long while). He was like 20 years old and his heart just stopped afaik, and he died.

Way too early to tell, they are still tweaking their lead compound, the one that will become RL-81.
He did say that he would be prioritizing safety, though so I'm sure it will be a factor.

 

[AtlasFainted]

They crank it up to 90dB? Welcome new worse tinnitus tone...

Yeah, I made an earlier post about not being able to hear frequencies after 9500 Hz according to online tests. I'm sure I must have had hearing loss before I got tinnitus, but since having a neurotoxic/ototoxic reaction my hearing must have gotten worse and my brain seems to have picked up on it and voila tinnitus. I just hope my tinnitus is at a frequency that FX-322 can reach.

They start at a lower volume and increase it (up to 90dB) until you can hear the sound.

But some people do report damage from the tests themselves, which is why I'm waiting until I can get FX-322 injected to get the extended audiogram.

I don't want to destroy what's left of my hearing in the higher frequencies during the process of trying to measure it, if there is nothing yet available (FX-322) to undo the damage before flat epithelia sets in.

If I get an extended audiogram, ideally it will be just a day or two (maybe even the same day) before I get the injection(s).

Personally my tinnitus started spontaneously a month after an acoustic trauma, and a few days before getting very sick. Though I can't be sure, I speculate that if I get even slight restoration near my tinnitus frequencies, it will turn itself off again.

 

[Danad]

I know many of us are looking for reasons that FX-322 may not work but I think it's important to review a few things. Tinnitus is merely a symptom of reduced auditory input incurred somewhere along the signal path. Central gain is compensatorily turned way upwards resulting in perception of the stochastic resonance, a feature used by our auditory systems providing an amazing amount of dynamic range. We are hardwired this way with varying degrees of sensitivity so manifestation of tinnitus is not uniform across the population. It has been shown that tympanoplasty, ear wax removal, even hearing aids can reduce/eliminate tinnitus. It makes good sense then to assume that reversing SNHL in the offending frequency range would be highly beneficial.

A few years ago when researching tinnitus it became painfully clear to me that without hearing restoration a cure would be unlikely. Attempts to alter the neuronal hyperactivity of a localized area of the brain, which is really just carrying out it's hardwired programming, is something, in my opinion , way beyond our current biotech.

 

[Flamingo1]

FREQ stock is tanking today and there has been a lot of insider selling by the directors, including Christopher Loose. Any idea what may be going on?

 

[Paulmanlike]

https://simplywall.st/stocks/us/pha...nasdaqfreq-insiders-been-selling-their-stock/

An insider selling off lots of stock... while it may not mean particularly anything, one may speculate otherwise.

 

[Emgee]

FREQ stock is tanking today and there has been a lot of insider selling by the directors, including Christopher Loose. Any idea what may be going on?

Loose's biggest trade to-date: 4,500 units of FREQ stock for $85,590 on 05/20.

 

[Nobody19]

Buy the dip!