Frequency Therapeutics — Hearing Loss Regeneration

[Ed209]

But we don't yet have the possibility to grow a limb back maybe if limbs could be grown back, people with phantom limb syndrome might be cured of that too. I know there have now been some successful limb transplants and some studies have shown that this resolved PLP. Maybe it can be the same with our ears.

I said similar qualities; they are not all exactly the same, but your point is valid.

They share similar underlying mechanisms and associated brain areas as tinnitus. PLP is just as misunderstood as well, as there is no accepted theory for why it happens, and there's no cure.

 

[Ed209]

There's also a theory about inflammation that could be the explanation for this too, if I'm not mistaken.

This could certainly be a reason for it happening in some cases, but you'll find that for a lot of people, sleep, or having a nap, can immediately spike their tinnitus quite significantly. Nobody knows why this occurs, but it's clearly something that is happening in the brain.

Some also notice that their tinnitus "fades in" as they awaken and become more consciously aware.

 

[HootOwl]

@Ed209, this is super random but can you pick a number for me between 1 and 15. I promise it's not for something weird.

 

[Ed209]

@Ed209, this is super random but can you pick a number for me between 1 and 15. I promise it's not for something weird.

3.

 

[NewLionel]

This could certainly be a reason for it happening in some cases, but you'll find that for a lot of people, sleep, or having a nap, can immediately spike their tinnitus quite significantly. Nobody knows why this occurs, but it's clearly something that is happening in the brain.

Some also notice that their tinnitus "fades in" as they awaken and become more consciously aware.

The map part is definitely true and the waking up and fading in...

Also when I drift off to sleep, my tinnitus goes away.

 

[Ed209]

The map part is definitely true and the waking up and fading in...

Also when I drift off to sleep, my tinnitus goes away.

That typo really threw me; I was thinking, "what map?"

Mine used to fade in as well for the first year or so. It doesn't anymore, it's just constant. Having a nap still affects me, though.

 

[Ehren M]

@Ed209, this is super random but can you pick a number for me between 1 and 15. I promise it's not for something weird.

5, unless it's actually for something weird, in which case: 1.5.

 

[Nathaniel Teposo]

The scientific world used to focus almost entirely on the ears when it came to tinnitus. It's only relatively recently that the brain became more of a focal point as our understanding improved. That's where the science led. Not everyone experiences ringing ears; for some, it's quite literally a ringing brain/head. I have both.

It's a valid point, however, to believe that by fixing the cochlea we could eliminate the tinnitus for some. I don't think it would help with chronic cases because there's too much evidence showing that eventually other parts of the brain take over and feed the auditory cortex, and the fact we perceive the sound also means that our higher consciousness is picking the signal up. There has to be something different going on in the brains of those with chronic cases because hearing loss alone cannot explain why it happens for some, but not for the majority.

It's interesting that tinnitus can be induced in those who don't have it via deep brain stimulation to the caudate body, and can be lowered and modulated in those who do have it. I think the network effect is so vast that it would be very difficult to fix chronic cases with hearing restoration alone. I understand what you are saying, though, that by repairing one of the primary sources it could induce some plasticity and return normal functioning to the brain. We won't truly know until we are capable of doing such things, and I don't think the data on cochlear implants is compelling enough.

Not entirely sure how to interpret this.

If you got your tinnitus from noise trauma, then curing hearing loss will definitely fix tinnitus. Just like my friend, who has moderate hearing loss in his left ear, when he got his hearing aid he can't notice his tinnitus or hear it much. So FX-322 will sure help to restore hearing and fix related tinnitus and I hope other forms of tinnitus too.

 

[Ed209]

@Ed209, this is super random but can you pick a number for me between 1 and 15. I promise it's not for something weird.

Will we ever learn what this is for?

 

[Ed209]

If you got your tinnitus from noise trauma, then curing hearing loss will definitely fix tinnitus. Just like my friend, who has moderate hearing loss in his left ear, when he got his hearing aid he can't notice his tinnitus or hear it much. So FX-322 will sure help to restore hearing and fix related tinnitus and I hope other forms of tinnitus too.

It's possible, but it's far from certain. I'm nonpartisan when it comes to this stuff because I'm clear in my posts that we just don't know. If strong evidence emerged that hearing restoration would cure noise-induced tinnitus, then I'd lean more in that direction. As it stands, there is no way of knowing, so anyone who refuses to hear other opinions, and is already sure that it will work, is biased.

 

[AfroSnowman]

It's possible, but it's far from certain. I'm nonpartisan when it comes to this stuff because I'm clear in my posts that we just don't know. If strong evidence emerged that hearing restoration would cure noise-induced tinnitus, then I'd lean more in that direction. As it stands, there is no way of knowing, so anyone who refuses to hear other opinions, and is already sure that it will work, is biased.

I'd feel better about our chances if there had been strong anecdotal reports from the previous clinical studies.

 

[Gb3]

@Ed209 start watching at the 52:29 mark.

 

[Chad Lawton]

Getting back to the discussion at hand: the problem I have with the idea of hearing restoration completely eradicating tinnitus is that there's no evidence that it will disrupt the network effect that a tinnitus brain usually develops. I think it will be better perceived with hearing aids and cochlear implants because you are improving the signal-to-noise ratio. Just the same as if you use earplugs; your tinnitus is going to rocket in volume for the reverse reason.

Most research indicates that tinnitus is generated by the brain when hearing loss occurs. Numerous imaging studies show this network effect, or centralisation, as some call it. Fatima Husain is a well-known researcher, and her work shows that there are key differences in the emotional centres of the brain of those with tinnitus compared with controls. There's also been observed differences in the white matter of the brain of those with chronic tinnitus. These are physical differences. The precuneus may also be involved in how tinnitus is perceived. Again, imaging studies have shown that it acts differently in tinnitus brains compared to non-tinnitus brains.

I'm surprised you make no mention of thalamocortical dysrhythmia. Long story short, it is the theory that when you deafferentate areas of the brain, they can no longer sync up properly in unison with the rest of the brain and you get a collision of brainwaves. Where this collision occurs you get the positive and negative traits of a number of neurological disorders. Hearing loss is the negative trait, tinnitus is the positive trait. Parkinson's' loss of motor control is the negative trait, shaking is the positive trait, etc. I'm a believer that if you can re-afferentate things, you can reduce the brain wave collisions and thus reduce the symptoms.

Thalamocortical dysrhythmia: a theoretical update in tinnitus

 

[Keith Handy]

As it stands, there is no way of knowing, so anyone who refuses to hear other opinions, and is already sure that it will work, is biased.

Projection ain't just a method of displaying images on a screen.

 

[Ed209]

@Ed209 start watching at the 52:29 mark.

It was interesting what they said about Parkinson's. I was aware that Deep Brain Stimulation treatments were used for it, but the part about trying to map the original signals from the lost cells was cool.

As far as tinnitus goes, they didn't discuss anything that we don't already know.

 

[Gb3]

It was interesting what they said about Parkinson's. I was aware that Deep Brain Stimulation treatments were used for it, but the part about trying to map the original signals from the lost cells was cool.

As far as tinnitus goes, they didn't discuss anything that we don't already know.

Did you hear them say "if they resolve hearing loss, then the tinnitus should go away"?

 

[star-affinity]

Did you hear them say "if they resolve hearing loss, then the tinnitus should go away"?

Interesting that they were just mentioning the hair cell loss and not synaptopathy with intact hair cells.

Also from Stanford:

 

[Ed209]

Did you hear them say "if they resolve hearing loss, then the tinnitus should go away"?

It doesn't make it true, though. That's not how science works, unfortunately. But, that's the nature of problems that are unsolved: everybody has an opinion on them.

There are various hypotheses out there because nobody knows at the end of the day. I remember when Ross O'Neill - the CEO of Neuromod - said he believed tinnitus could be resolved if we could restore hearing loss. He then gave an analogy about a hosepipe being blocked (or something along those lines). This was during an interview with @Hazel on the Tinnitus Talk Podcast. I've heard various opinions from academics over the years, but there's nothing that's concrete.

There's validity to both sides of the argument; I just happen to lean one way more than the other, and I also like to challenge the views of those who are sure of themselves.

 

[Ed209]

I'm surprised you make no mention of thalamocortical dysrhythmia. Long story short, it is the theory that when you deafferentate areas of the brain, they can no longer sync up properly in unison with the rest of the brain and you get a collision of brainwaves. Where this collision occurs you get the positive and negative traits of a number of neurological disorders. Hearing loss is the negative trait, tinnitus is the positive trait. Parkinson's' loss of motor control is the negative trait, shaking is the positive trait, etc. I'm a believer that if you can re-afferentate things, you can reduce the brain wave collisions and thus reduce the symptoms.

Thalamocortical dysrhythmia: a theoretical update in tinnitus

Sorry, I missed this post. It's funny you brought this up because I remember reading something about this years ago in a report by Dirk De Ridder. I did a quick Google, and here it is:

Thalamocortical dysrhythmia: a theoretical update in tinnitus

 

[Ed209]

Projection ain't just a method of displaying images on a screen.

How is psychological projection relevant to this thread? I assume that is what you're referring to?

 

[Foamearplugssuck]

I hope I'm reading incorrectly. Please someone tell me that my reading comprehension skills got fucked up in a bizarre turn of events and I come to only understand the opposite of things.

Investigation announced for Long-Term Investors in Frequency Therapeutics, Inc. (NASDAQ: FREQ) over potential Wrongdoing

According to that complaint filed in the U.S. District Court for the District of Massachusetts the plaintiff alleges that the defendants made false and/or misleading statements and/or failed to disclose that Frequency's development and commercialization of a hearing loss treatment titled "FX-322" was not producing the results Frequency desired, that FX-322's ongoing clinical study was not as positive as Frequency portrayed, and that as a result of the foregoing, defendants' positive statements about Frequency's business, operations, and prospects were materially misleading and/or lacked a reasonable basis.

Great, great, great, sounds fucking great. All the hope and buzz was nice while it lasted.

*Turns to Otonomy*

 

[Diesel]

I hope I'm reading incorrectly. Please someone tell me that my reading comprehension skills got fucked up in a bizarre turn of events and I come to only understand the opposite of things.

Investigation announced for Long-Term Investors in Frequency Therapeutics, Inc. (NASDAQ: FREQ) over potential Wrongdoing

Great, great, great, sounds fucking great. All the hope and buzz was nice while it lasted.

*Turns to Otonomy*

View attachment 46789

This is old news. It has been going on since March, and heavily discussed here, and mentioned in the firm's quarterly filing to investors.

Yet, the severe trial still has results TBD, they have an upcoming R&D event, and are planning a second Phase 2 for FX-322 to be announced in Q4.

 

[Foamearplugssuck]

This is old news. It has been going on since March, and heavily discussed here, and mentioned in the firm's quarterly filing to investors.

.........oh.

I got it as a Google alert last night, so I assumed otherwise. I'll have to do a better job of searching for mentions of these kinds of updates on here in the future.

 

[tommyd87]

.........oh.

I got it as a Google alert last night, so I assumed otherwise. I'll have to do a better job of searching for mentions of these kinds of updates on here in the future.

Not to mention that there tends to be little merit to their claims and little evidence it will succeed either. Essentially it just looks like they are fishing for claims. They are going to have to demonstrate that Frequency Therapeutics exaggerated claims and presently there is very little evidence to say they did, and no statements from this group to say why Frequency Therapeutics did either.

 

[r34d1ng]

Frequency Therapeutics Announces New FX-322 Results Showing That Additional Study Participants Gain Hearing Improvements at Later Time Points

LEXINGTON, Mass.--(BUSINESS WIRE)--Sep. 22, 2021-- Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage regenerative medicine company focused on developing therapeutics to activate a person's innate regenerative potential to restore human function, today announced that four additional sensorineural hearing loss (SNHL) subjects from its FX-322-111 open-label study achieved statistically significant hearing improvements when evaluated 8 to 12 months following initial dosing.

Including the five initial responders, there are now a total of nine subjects that participated in the FX-322-111 study (n=32) that have been shown to have statistically significant improvements in word recognition scores, a key measure of speech perception, at time points between 90 days and one year.

These new results suggest that the hearing of individuals administered with a single dose of FX-322 may improve over extended periods. The longer-term measures of their treated ear demonstrated word recognition score improvements when compared to pre-treatment baseline levels and no significant changes were detected in their untreated ears. Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance.

[...]

 

[Diesel]

Frequency Therapeutics Announces New FX-322 Results Showing That Additional Study Participants Gain Hearing Improvements at Later Time Points

LEXINGTON, Mass.--(BUSINESS WIRE)--Sep. 22, 2021-- Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage regenerative medicine company focused on developing therapeutics to activate a person's innate regenerative potential to restore human function, today announced that four additional sensorineural hearing loss (SNHL) subjects from its FX-322-111 open-label study achieved statistically significant hearing improvements when evaluated 8 to 12 months following initial dosing.

Including the five initial responders, there are now a total of nine subjects that participated in the FX-322-111 study (n=32) that have been shown to have statistically significant improvements in word recognition scores, a key measure of speech perception, at time points between 90 days and one year.

These new results suggest that the hearing of individuals administered with a single dose of FX-322 may improve over extended periods. The longer-term measures of their treated ear demonstrated word recognition score improvements when compared to pre-treatment baseline levels and no significant changes were detected in their untreated ears. Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance.

[...]

Looking forward to seeing that data.

 

[rei]

Looks like the ear fertilizer needs a little time to get the lawn growing. Today is a good day.

 

[Zugzug]

Frequency Therapeutics Announces New FX-322 Results Showing That Additional Study Participants Gain Hearing Improvements at Later Time Points

LEXINGTON, Mass.--(BUSINESS WIRE)--Sep. 22, 2021-- Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage regenerative medicine company focused on developing therapeutics to activate a person's innate regenerative potential to restore human function, today announced that four additional sensorineural hearing loss (SNHL) subjects from its FX-322-111 open-label study achieved statistically significant hearing improvements when evaluated 8 to 12 months following initial dosing.

Including the five initial responders, there are now a total of nine subjects that participated in the FX-322-111 study (n=32) that have been shown to have statistically significant improvements in word recognition scores, a key measure of speech perception, at time points between 90 days and one year.

These new results suggest that the hearing of individuals administered with a single dose of FX-322 may improve over extended periods. The longer-term measures of their treated ear demonstrated word recognition score improvements when compared to pre-treatment baseline levels and no significant changes were detected in their untreated ears. Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance.

[...]

Here's what confuses me. Four out of four available responders return at months 8-12 and see enough regression to be within their baseline margin of error. So in one breath, they are saying gains are maxed at a few months before they become trivial.

Then they are also saying that four different patients saw their major improvements later on that were observed at months 8-12. Are we to then predict that at months ~16-24 (so 8-12 months after their "response" recording at 8-12 months), these people should also regress to their original baseline margin of error?

What are we seeing here? It doesn't make any sense to me. So an equal number of people improve as regress in an open-label study. Seems pretty unclear if this means anything.

 

[F-u-T]

Looking forward to seeing that data.

Is this good news? Curious why the stock dipped on this news. I would think it would be positive but I digress.

 

[Jurger]

Frequency Therapeutics Announces New FX-322 Results Showing That Additional Study Participants Gain Hearing Improvements at Later Time Points

LEXINGTON, Mass.--(BUSINESS WIRE)--Sep. 22, 2021-- Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage regenerative medicine company focused on developing therapeutics to activate a person's innate regenerative potential to restore human function, today announced that four additional sensorineural hearing loss (SNHL) subjects from its FX-322-111 open-label study achieved statistically significant hearing improvements when evaluated 8 to 12 months following initial dosing.

Including the five initial responders, there are now a total of nine subjects that participated in the FX-322-111 study (n=32) that have been shown to have statistically significant improvements in word recognition scores, a key measure of speech perception, at time points between 90 days and one year.

These new results suggest that the hearing of individuals administered with a single dose of FX-322 may improve over extended periods. The longer-term measures of their treated ear demonstrated word recognition score improvements when compared to pre-treatment baseline levels and no significant changes were detected in their untreated ears. Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance.

[...]

Great news, and then this in the middle of the press release:

"Of the five subjects that had a statistically significant response at day-90, the four that returned for evaluation had scores that remained above their baseline word recognition measures, though were below the threshold for statistical significance."

What the hell is going on with this drug?