Frequency Therapeutics — Hearing Loss Regeneration

[scotty03874]

Very true. So yesterday it was selling at $54.38 per share?

That was on the 8th, yesterday. I bought 109 more shares ,some at $50.13. I have a total of 200 shares now. I'm going to sit back and watch for now and wait for the upcoming Phase 2a news. Unless it drops under $45.00 in the coming weeks, then I'll probably buy some more.

 

[twa]

That was on the 8th, yesterday. I bought 109 more shares ,some at $50.13. I have a total of 200 shares now. I'm going to sit back and watch for now and wait for the upcoming Phase 2a news. Unless it drops under $45.00 in the coming weeks, then I'll probably buy some more.

That's great, hopefully it will be successful therapeutically and financially.

 

[dd314]

I don't know why researchers have such a hard time with tinnitus. In my opinion it is caused by hearing loss; period.

Yes you have an occasional person with TMJ or some weird condition, but most of the people on the board have tinnitus from hearing loss. Whether it be hidden hearing loss or shown in the audiogram, they have it.

I honestly believe that if the hair cells and synapses can be restored most will see massive improvements with longer term improvements to follow. The brain would have no reason to ring/roar/screech or hiss if it receives the signals it requires.

Honestly I think after treatment the brain will need time to readjust to seeing the signals it has been previously looking for.

Hopefully these new treatments will prove not to let tinnitus be a death sentence any longer.

There are still unknowns there. I'm really, really hoping this drug reduces tinnitus, but it is baffling that most people with hearing loss don't have tinnitus; the figure I've seen is 30%, and that's just from the first Google result. The two explanations would be that synapse damage is a key difference, or that some brains are just better at dealing with lost input than others. That's assuming the increased gain/stochastic resonance theory is correct. Hopefully either FX-322 or OTO-413 can do the job.

 

[Jack V]

ASSUMING... FX-322 works, is safe, is approved, AND...

ASSUMING... You invest in FREQ and make a bunch of money...

... you should use your profits to pay for the treatment.

There's just a sweet logic to that.

 

[FGG]

There are still unknowns there. I'm really, really hoping this drug reduces tinnitus, but it is baffling that most people with hearing loss don't have tinnitus; the figure I've seen is 30%, and that's just from the first Google result. The two explanations would be that synapse damage is a key difference, or that some brains are just better at dealing with lost input than others. That's assuming the increased gain/stochastic resonance theory is correct. Hopefully either FX-322 or OTO-413 can do the job.

Some people have more "predictive brains" than others so the mismatch to expected sound and sound triggers tinnitus in those people with less damage. Dr. Will Sedley talks about that.

Similarly, not everyone who loses a limb gets "phantom limb" but restoring the input in those that do (with mirror therapy) helps the brain receive the lost input.

 

[dd314]

Some people have more "predictive brains" than others so the mismatch to expected sound and sound triggers tinnitus in those people with less damage. Dr. Will Sedley talks about that.

Similarly, not everyone who losses a limb gets "phantom limb" but restoring the input in those that do (with mirror therapy) helps the brain receive the lost input.

Interesting. The phantom limb syndrome is actually experienced by a vast majority of amputees however; it's like 90%. But there are a lot more nerve cells being lost with an amputation than with hearing loss, so maybe that makes sense. I do have a feeling that one of these drugs is going to work for some people, just worth acknowledging the fact. Personally I feel that chronic inflammation is also a key player.

 

[FGG]

Interesting. The phantom limb syndrome is actually experienced by a vast majority of amputees however; it's like 90%. But there are a lot more nerve cells being lost with an amputation than with hearing loss, so maybe that makes sense. I do have a feeling that one of these drugs is going to work for some people, just worth acknowledging the fact. Personally I feel that chronic inflammation is also a key player.

I think chronic neuroinflammation is part of the reactive/severity puzzle for sure. And in some cases, it may be most of the picture, especially when there is less structural damage.

 

[FGG]

How I have put this all together in my mind, simplified (I am going to go ahead and anthropomorphize the brain for ease of explaining):

You have two basic neurotransmitters at play here (others are involved but these are the main ones): GABA and Glutamate.

Glutamate is your main excitatory neurotransmitter for nerve signals and GABA is your inhibitory one.

You need both in balance and both are present throughout your body (everything from your muscles to your pancreas).

In the hearing pathways, you have these receptors in both your cochlea and in the higher auditory processing centers centrally.

Acutely after injury (e.g., noise, toxin, etc), your IHCs dump too much Glutamate at once and your NMDA receptors are overstimulated and oversensitized. There is other damage too directly to structures but keeping it simple...

This excess neuroexcitability from this excess Glutamate gets propagated up the auditory pathway. For some people, when this normalizes, they get improvements.

There are mechanisms to propagate this overexcitability past the acute phase, though. Chronic inflammation will do this (normally inflammation is self limiting unless you have a continued stimulus, e.g., autoimmunity, allergy, or viral etc etc). Severe, uncoping stress will also change your immune profile to favor Glutamate over GABA. In addition, stress causes the release of dynorphins into the cochlea (from axons traveling from the brain) and these can sensitized the NMDA receptors further (I suspect that's why people who have tinnitus and are severely stressed are more prone to noise injury from quieter noises than previously).

Anyway, in addition, if you have a predictive brain there is a greater mismatch between what the brain "expects" and the sound it hears (a popular example of how the brain can change perception in the visual system is the color changing dress).

When the predictive brain gets a mismatch, it doesn't like it and tries to reconcile this by "pushing" the system for more input with more Glutamate to increase the signal. This obviously doesn't work with hearing damage (or hearing interference) because the signal is broken but the brain keeps trying.

That's my take anyway. Thoughts?

 

[Pharz]

This is my favorite thread. I come here the nights that my tinnitus peaks and read the messages to distract me and give me hope. Eventually I fall asleep.

 

[grate_biff]

There are still unknowns there. I'm really, really hoping this drug reduces tinnitus, but it is baffling that most people with hearing loss don't have tinnitus; the figure I've seen is 30%, and that's just from the first Google result. The two explanations would be that synapse damage is a key difference, or that some brains are just better at dealing with lost input than others. That's assuming the increased gain/stochastic resonance theory is correct. Hopefully either FX-322 or OTO-413 can do the job.

I think the main reason for developing tinnitus or not is how big a gap you have in your hearing. If the loss is very even, chances are you will not develop tinnitus. The brain tries to fill in the gaps.

I think my audiogram is an example of that.

 

[Jrblovsky]

I think the main reason for developing tinnitus or not is how big a gap you have in your hearing. If the loss is very even, chances are you will not develop tinnitus. The brain tries to fill in the gaps.

I think my audiogram is an example of that.

View attachment 43273

I envy all you guys that can hear high tones. I can barely hear 8 kHz in my right ear.

 

[Keith Handy]

This is my favorite thread. I come here the nights that my tinnitus peaks and read the messages to distract me and give me hope. Eventually I fall asleep.

Seriously! I went back to the posts from around the time just preceding my onset, and read through them all to the present day to get a sense of what was being talked about while all of this was happening in my life.

 

[L34]

Glutamate is your main excitatory neurotransmitter for nerve signals and GABA is your inhibitory one.

You need both in balance and both are present throughout your body (everything from your muscles to your pancreas).

Acutely after injury (e.g., noise, toxin, etc), your IHCs dump too much Glutamate at once and your NMDA receptors are overstimulated and oversensitized. There is other damage too directly to structures but keeping it simple...

Very nice writing, thank you so much.

So in theory, for some of us it should be helpful to lower Glutamate and increase GABA. But it is probably not that simple? I will do some searching on that topic...

This excess neuroexcitability from this excess Glutamate gets propagated up the auditory pathway. For some people, when this normalizes, they get improvements.

Do you happen to have info on the timeframe of this? Is the window for improving a week or maybe much longer? Thank you so much

 

[Diesel]

I think the main reason for developing tinnitus or not is how big a gap you have in your hearing. If the loss is very even, chances are you will not develop tinnitus. The brain tries to fill in the gaps.

I think my audiogram is an example of that.

View attachment 43273

Question: Do you experience your tinnitus in the range where you have the deficit? IE: Does your tinnitus *sound like* that high frequency range?

 

[grate_biff]

Question: Do you experience your tinnitus in the range where you have the deficit? IE: Does your tinnitus *sound like* that high frequency range?

I've matched my tinnitus to be around 12,500 Hz in my right ear.

The point with my post was that I only have tinnitus in my right ear where you see the stern decline in hearing (gap). Even with slightly more severe hearing loss in my left ear, I have no tinnitus.

 

[FGG]

Very nice writing, thank you so much.

So in theory, for some of us it should be helpful to lower Glutamate and increase GABA. But it is probably not that simple? I will do some searching on that topic...

Do you happen to have info on the timeframe of this? Is the window for improving a week or maybe much longer? Thank you so much

Unfortunately, not that simple for a few reasons:

One is that the entire body uses these neurotransmitters and Glutamate blockers (for instance) have systemic side effects and comparatively much less makes it through either the blood brain barrier or the blood cochlear layer.

The other issue is that these receptors are regulated by the body. So, over time, you can change your receptor numbers. This is why GABA drugs like Benzos help acutely but when you develop tolerance they can lose effectiveness or make a rebound worsening when your inhibitory sites (receptors) aren't as responsive to GABA (or there are just less of them).

To lower excess cochlear Glutamate: reduce cochlear inflammation. Protect your ears, avoid comorbidities that increase systemic inflammation (e.g., allergies, viral infections, etc) and manage stress (this takes a long time to normalize the effects of it). These will help to a variable degree (not a cure) and may prevent a worsening.

The best treatments will obviously be restoring normal input/structures (e.g., FX-322, OTO-413) and also reducing the effects of Glutamate hyperexcitabilty.

Sound has an oral drug in trials with unusually good cochlear penetrance which should help with neuroexcitability through other means (Glutathione perioxidase inducer among other things). I think it has real potential.

Otonomy has an intratympanic NMDA receptor blocker, which should help acutely and maybe even in cases chronically where the receptor is continually oversensitized (vs. structural damage and the predictive brain mismatch being the more salient factor).

No one knows the time frame of the acute vs chronic changes as far as I know. Perhaps the data on OTO-313 will help people figure it out. Though I suspect there are individual factors too.

 

[wwtsai]

I think the main reason for developing tinnitus or not is how big a gap you have in your hearing. If the loss is very even, chances are you will not develop tinnitus. The brain tries to fill in the gaps.

I think my audiogram is an example of that.

I must be one of the unfortunate ones then as my losses are pretty much the same in both ears

 

[FGG]

I must be one of the unfortunate ones then as my losses are pretty much the same in both ears

My ears are the same bilaterally, too.

 

[grate_biff]

Acutely after injury (e.g., noise, toxin, etc), your IHCs dump too much Glutamate at once and your NMDA receptors are overstimulated and oversensitized

So ATP is some form of Glutamate?

 

[Philip83]

I must be one of the unfortunate ones then as my losses are pretty much the same in both ears

I think he means even across the frequencies, not between the ears. My hearing loss is fairly equally bilateral too, and I have a freakin' orchestra of different tones and hisses in my head/ears.

I think what mostly matters is how quickly and/or severe the trauma on your cells/synapses are. A very slow grind over time is more likely to produce hearing loss without tinnitus.

 

[Paulmanlike]

@FGG, congratulations on buying the IPO. A 4 bagger already and you don't day trade.

I was buying and selling on the fluctuations and with the profits I made I reinvested it all back into Frequency Therapeutics. Pretty much doubled my position.

I figure if you're a regular here who invests your time into learning about your condition and you have cash to invest, then this is the stock for you. Although I've seen biotechs crash in a blink of an eye - be prepared to lose most of it but the rewards can be big. You deserve it though knowing that most biotechs burn through millions of investors' cash and some end up with zero products.

Emotional investment set aside, I have faith in Robert Langer and David Lucchino.

I try to keep my emotional investment and financial judgement apart on this one.

 

[Keith Handy]

 

[FGG]

So ATP is some form of Glutamate?

No. ATP is not a neurotransmitter. It's an "energy source" compound.

 

[Danad]

How I have put this all together in my mind, simplified (I am going to go ahead and anthropomorphize the brain for ease of explaining):

You have two basic neurotransmitters at play here (others are involved but these are the main ones): GABA and Glutamate.

Glutamate is your main excitatory neurotransmitter for nerve signals and GABA is your inhibitory one.

You need both in balance and both are present throughout your body (everything from your muscles to your pancreas).

In the hearing pathways, you have these receptors in both your cochlea and in the higher auditory processing centers centrally.

Acutely after injury (e.g., noise, toxin, etc), your IHCs dump too much Glutamate at once and your NMDA receptors are overstimulated and oversensitized. There is other damage too directly to structures but keeping it simple...

This excess neuroexcitability from this excess Glutamate gets propagated up the auditory pathway. For some people, when this normalizes, they get improvements.

There are mechanisms to propagate this overexcitability past the acute phase, though. Chronic inflammation will do this (normally inflammation is self limiting unless you have a continued stimulus, e.g., autoimmunity, allergy, or viral etc etc). Severe, uncoping stress will also change your immune profile to favor Glutamate over GABA. In addition, stress causes the release of dynorphins into the cochlea (from axons traveling from the brain) and these can sensitized the NMDA receptors further (I suspect that's why people who have tinnitus and are severely stressed are more prone to noise injury from quieter noises than previously).

Anyway, in addition, if you have a predictive brain there is a greater mismatch between what the brain "expects" and the sound it hears (a popular example of how the brain can change perception in the visual system is the color changing dress).

When the predictive brain gets a mismatch, it doesn't like it and tries to reconcile this by "pushing" the system for more input with more Glutamate to increase the signal. This obviously doesn't work with hearing damage (or hearing interference) because the signal is broken but the brain keeps trying.

That's my take anyway. Thoughts?

It is also noteworthy that tinnitus can develop from just reduced auditory input such as with earwax, sound deprivation etc. with no injury from sound or toxins.

 

[FGG]

It is also noteworthy that tinnitus can develop from just reduced auditory input such as with earwax, sound deprivation etc. with no injury from sound or toxins.

Oh definitely. Anything that interferes with auditory input.

But in those cases, you can immediately reverse it. They are a nice example of tinnitus not being "stuck" in the brain though.

 

[Jrblovsky]

There are still unknowns there. I'm really, really hoping this drug reduces tinnitus, but it is baffling that most people with hearing loss don't have tinnitus; the figure I've seen is 30%, and that's just from the first Google result. The two explanations would be that synapse damage is a key difference, or that some brains are just better at dealing with lost input than others. That's assuming the increased gain/stochastic resonance theory is correct. Hopefully either FX-322 or OTO-413 can do the job.

I feel most who have noise-induced hearing loss from long-term exposure to loud noise over periods of years to decades have less tinnitus or none at all. This is compared to many with loud abrupt exposures. Gunfire, explosions, loud concerts, bars, iPods to maximum volume for hours.

Just my take on it.

 

[Diesel]

There are still unknowns there. I'm really, really hoping this drug reduces tinnitus, but it is baffling that most people with hearing loss don't have tinnitus; the figure I've seen is 30%, and that's just from the first Google result. The two explanations would be that synapse damage is a key difference, or that some brains are just better at dealing with lost input than others. That's assuming the increased gain/stochastic resonance theory is correct. Hopefully either FX-322 or OTO-413 can do the job.

I have a BIG BIG problem with this "30% of people with hearing loss have tinnitus" stat that surfaces on this thread about every month. The main issue I have is what is considered "hearing loss." How many people come on this forum every day who explain their ENT said they "don't have hearing loss, but have tinnitus." This includes me.

I now know that it is because my hearing was originally only checked up to 8 kHz. And that's the "standard" for hearing loss. BUT, it turns out I do have losses in the extended range (8 kHz+).

So, that statistic fails to capture those that are "normal" on the standard (up to 8 kHz) test; but have poor extended hearing and tinnitus.

I suspect that the addressable "tinnitus + ok standard hearing" market is being grossly under-represented/under-studied. Therefore, this may be a hidden opportunity for FX-322 if the TFI score look promising.

 

[dd314]

I have a BIG BIG problem with this "30% of people with hearing loss have tinnitus" stat that surfaces on this thread about every month. The main issue I have is what is considered "hearing loss." How many people come on this forum every day who explain their ENT said they "don't have hearing loss, but have tinnitus." This includes me.

I now know that it is because my hearing was originally only checked up to 8 kHz. And that's the "standard" for hearing loss. BUT, it turns out I do have losses in the extended range (8 kHz+).

So, that statistic fails to capture those that are "normal" on the standard (up to 8 kHz) test; but have poor extended hearing and tinnitus.

I suspect that the addressable "tinnitus + ok standard hearing" market is being grossly under-represented/under-studied. Therefore, this may be a hidden opportunity for FX-322 if the TFI score look promising.

Then I guess the figure is "30% of people with non-hidden/lower-frequency/noticeable hearing loss", and it's still baffling to be honest.

 

[Philip83]

I suspect that the addressable "tinnitus + ok standard hearing" market is being grossly under-represented/under-studied. Therefore, this may be a hidden opportunity for FX-322 if the TFI score look promising.

Yep, this is something I can see (and hope) them amping up their communication about once they have some hard data. There is no other compound with a double blind placebo controlled trial to back it up to treat tinnitus. That's thousands and of thousands of additional costumers that might not have been seeking help were it only for their acquired hearing loss.

 

[ThomasRobert]

FREQ Frequency Therapeutics price target raised to $68 from $48 at Oppenheimer.

Oppenheimer analyst Jay Olson raised the firm's price target on Frequency Therapeutics to $68 from $48 and keeps an Outperform rating on the shares. Ahead of FX-322 Phase 2a Day-90 interim read-out, the analyst points out an exploratory efficacy endpoint in the study that could potentially lead to unlocking additional potential in tinnitus. Currently, there are no FDA-approved therapeutics for tinnitus, he adds. Based on the FX-322 mechanism in the context of putative pathology of tinnitus, Olson believes there's a reasonable chance that FX-322 can benefit at least a subgroup of tinnitus sufferers.

Link:
Oppenheimer Believes Frequency Therapeutics (FREQ) Won't Stop Here