Frequency Therapeutics — Hearing Loss Regeneration

#20,101
@dam said:
Though if this is true, it kind of makes me wonder what the point of FX-345 was at all.
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Precisely. No one has explained to me why they'd bifurcate their time and money. Perhaps some flaw was discovered or at least strongly suspected with the core approach to the formulation or delivery of the entire candidate line, but absent any knowledgeable scientific opinion on that, I have to conclude by Occam's Razor that it was a business risk analysis. Would be a shame if there is a useful therapy left on the table because FREQ simply poisoned the well by bad leadership. So my question stands.
 
#20,102
jaytee said:
Precisely. No one has explained to me why they'd bifurcate their time and money. Perhaps some flaw was discovered or at least strongly suspected with the core approach to the formulation or delivery of the entire candidate line, but absent any knowledgeable scientific opinion on that, I have to conclude by Occam's Razor that it was a business risk analysis. Would be a shame if there is a useful therapy left on the table because FREQ simply poisoned the well by bad leadership. So my question stands.
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FX-345 was almost identical to FX-322. There was only a very small molecular difference. It was highly unlikely to succeed since the parent compound didn't either.

A flaw was discovered. Multiple times, in fact. Several failed clinical trials. It just doesn't work. It doesn't have anything to do with the leadership. Scientifically, it failed.
 
#20,103
SmallRonnie said:
FX-345 was almost identical to FX-322. There was only a very small molecular difference. It was highly unlikely to succeed since the parent compound didn't either.

A flaw was discovered. Multiple times, in fact. Several failed clinical trials. It just doesn't work. It doesn't have anything to do with the leadership. Scientifically, it failed.
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So the drug worked on cadavers and mice, was injected to people who were about to get cochlear implants so the scientists could see it went where needed. But it still failed...

I'm still lost on how this worked on cadavers but not living people.
 
#20,104
JimmyStrong said:
So the drug worked on cadavers and mice, was injected to people who were about to get cochlear implants so the scientists could see it went where needed. But it still failed...

I'm still lost on how this worked on cadavers but not living people.
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Because cadavers and ex-vivo versus in-vivo are two completely different things. There was likely some cell activation in the study participants that may have developed into new stereocilia (as per the ex-vivo examples), but do we know if healthy synaptic connections were developing, and was there a signal being developed between the brain and the new cells?

A dead person can't tell you this, for example, but a living person can.

I once asked these very questions, but was met with unnecessary animosity. This part of the discussion can be found on pages 91 and 92 (after doing a quick keyword search):

Page 91: Frequency Therapeutics — Hearing Loss Regeneration

Unfortunately, there is no way of taking a clear image of the inside of a living cochlear, so we won't know for sure if new stereocilia had developed inside the study participants. We do know that this can be done ex-vivo, though, so it depends entirely upon the delivery method and the depth to which the drug penetrated the inner ear.

What we know for sure is that the trial failed as it showed no efficacious advantage over a placebo. I found the previous trial results to be very underwhelming, but this didn't stop the hype from continuing to grow based on some very flimsy evidence.
 
#20,105
JimmyStrong said:
So the drug worked on cadavers and mice, was injected to people who were about to get cochlear implants so the scientists could see it went where needed. But it still failed...

I'm still lost on how this worked on cadavers but not living people.
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This was huge progress towards curing hearing loss. It would be worth it for another biotech company or U.S government/military scientists to keep studying this drug and figure out what needs to be changed to get it to work.
 
#20,106
RingingBrother said:
This was huge progress towards curing hearing loss. It would be worth it for another biotech company or U.S government/military scientists to keep studying this drug and figure out what needs to be changed to get it to work.
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It definitely needs exploring, but unfortunately, hearing loss and tinnitus aren't seen as being sexy enough for the big research dollars. We are at the bottom of the pile along with a load of other health conditions all fighting for whatever scraps we can get.

I'd love nothing more than to see a breakthrough in tinnitus and hearing related research. We could all attend a silent party to celebrate :D
 
#20,107
I know forums are a place of discussion, but I wish this thread would just die, like the drug. It doesn't deserve to be placed at the top of the Research News sub-forum with each new post.
 
#20,108
Ed209 said:
It definitely needs exploring, but unfortunately, hearing loss and tinnitus aren't seen as being sexy enough for the big research dollars. We are at the bottom of the pile along with a load of other health conditions all fighting for whatever scraps we can get.

I'd love nothing more than to see a breakthrough in tinnitus and hearing related research. We could all attend a silent party to celebrate :D
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I can see the U.S. military having an interest due to combat related hearing loss.
 
#20,110
Ed209 said:
This post perfectly sums up what many of us have been saying for years. People were convinced about FX-322, believing it to be a miracle cure before any of the results had even come out. I still remember the days of @JohnAdams wanting a petition for its immediate release on special measures because of the overwhelming "evidence." This is the unfortunate effect of getting all one's information from an echo chamber. Even though their results were terrible, and the management had dumped all their shares on the retail traders, many continued to defend the company.

People's analysis became too emotionally biased rather than objective, and that's when I stopped following this thread.

I feel so sorry for all those who put all their eggs in this basket.

100%.
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To shield oneself from one disappointment, people were then telling themselves that if one of these treatments don't pan out, another will, and very soon. The user @weab00's reasoning in 2020 seemed contingent on nothing but optimism and hope. I'm not sure if he was serious or tongue-in-cheek, but he seems to have had his hopes tempered in 2022.
weab00 said:
And of course, we have biotechs like Frequency Therapeutics and Otonomy looking to regenerate the cochlea, as well as Sound Pharmaceuticals who are in stage 3 clinical trials for a Menière's drug that's been shown to reduce cochlear inflammation and help with tinnitus/hyperacusis in mice.

My point is that there's help coming very soon, just stick it out for a few more years and I think there's a high chance at least one of these companies will work; FX-322 is already effective for sensorineural hearing loss.
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weab00 said:
Seems like we are agonizingly close to an effective remedy for tinnitus/hyperacusis. Now it's the waiting game, hoping for 2023.
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#20,111
#20,113
According to his Linkedin, Will McLean (on whose research FX-322 was founded on) left Frequency Therapeutics in April 2022 and is now Chief Scientific Officer at a new (unnamed) company. According to his profile, he is still working on regenerative medicine to restore hearing.
 
#20,116
Why did Will McLean leave Frequency Therapeutics at that (crucial) time, one wonders?

They say that rats desert a sinking ship.

With all the failed research in the past year, along with plenty of money being passed around, you have to question if this research is just money making scheme; a game that fools people with false hope.

A cure for tinnitus and/or hearing loss would truly be life changing for millions. I wonder if that's what people like Will McLean continue to thrive on.

Perhaps he realised a year ago that things were getting a bit 'close to the bone' and it was time to move onto a new job? It was time to ensure his financial future beyond his knowledge of the forthcoming failure of FX-322?

No doubt he'll leave this new company in a similar fashion when it's time to move on again.

Well done to him, he's fooling everyone while lining his pockets with money.

Not fooling me now, I've seen enough of this.

I think the best we'll see in the next 20 years or so is a pill taken regularly that effectively reduces tinnitus without any major side effects. I don't think there will be anything to cure hearing loss for a long, long time.

But as for regenerative medicine; this just ain't happening. They can't see inside the skull, they can't properly scan the auditory system and they can't deliver drugs with proper accuracy. And that's just for starters. It's a total shotgun-in-the-dark approach, a hope and a prayer.

There's a reason why Otonomy and Frequency Therapeutics gave up and sold their research findings for next to nothing. It's obvious they weren't even close. No, scrub that, they weren't even on the right track or ball park or possibly the right planet?

I've no doubt some group of scientists will figure this out eventually as birds, fish and reptiles regrow hair cells automatically. It's just going to take decades to first of all figure out why/how it works and then there is transposing that natural biological mechanism to work on a different species (a human). This I believe is the current 'best' hope. The resultant medicine could take the form of a 'hearing loss prevention' jab that children get in schools: a message delivered to the auditory system, that allows hair cells to repair and regenerate just like other cells in the body. So children can grow up and abuse their ears all they want knowing any hearing loss or tinnitus are only temporary and will heal within weeks.

Right now though, I think regenerative medicine is barking up the wrong tree. They may as well be researching a potion to give eternal life or resurrect the dead.
 
#20,117
Jupiterman said:
They may as well be researching a potion to give eternal life
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I believe some buncha scientists have been working on extending life for a decade or two now. One of them found the secret to eternal life, but sadly he died (and never told anyone the secret) :)

Imitating Nature, that's the way most human innovations succeed.
 
#20,119
RingingBrother said:
There's a chance we might get some random good news of long term improvement in trial subjects and resumption of trials.
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Maybe the trial wasn't long enough? A long time ago I severed the tip of my finger. I was told it would take about 2 years for sensation to come back after it was reattached. Guess what happened - some feeling came back after 2 years. It still feels a little odd, but it came back. I wonder if it simply takes a while for the nerves to re-attach?
 
#20,120
Cernuto said:
Maybe the trial wasn't long enough? A long time ago I severed the tip of my finger. I was told it would take about 2 years for sensation to come back after it was reattached. Guess what happened - some feeling came back after 2 years. It still feels a little odd, but it came back. I wonder if it simply takes a while for the nerves to re-attach?
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Nerves can be regrown with stem cell treatment. They are very slow to regrow. It takes several months.

I actually severed a nerve in my finger too but never got the feeling back in it even years later. I will be going for stem cell therapy soon so maybe that will get some back but I'm hoping it will regrow some of the nerves in my ear mostly.
 
#20,121
SmallRonnie said:
Nerves can be regrown with stem cell treatment. They are very slow to regrow. It takes several months.

I actually severed a nerve in my finger too but never got the feeling back in it even years later. I will be going for stem cell therapy soon so maybe that will get some back but I'm hoping it will regrow some of the nerves in my ear mostly.
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I had a digit 90% severed, nerves, tendons cut off completely. Hanging on the skin. After reattachment, I have like 85% of the feeling back after a few months. It's slightly weird, but fine.
 
#20,122
I finished watching the film "Sound of Metal". I won't lie, after watching that film I feel a bit sad and really angry towards FREQ for promising the world to us and failing to deliver. And my heart also goes out to those with severe to profound hearing loss. It's really a shame that we live in a world with nothing to help conditions such as this.
 
#20,123
Hearing loss and dementia. Two human conditions where you'd think that just a leeetle bit of government financing and proactivity could do a huge amount of good. Yet the heavy lifting is left to dinky little startups looking for their pot of gold at the end of the rainbow.
 
#20,124
d'Wooluf said:
Hearing loss and dementia. Two human conditions where you'd think that just a leeetle bit of government financing and proactivity could do a huge amount of good. Yet the heavy lifting is left to dinky little startups looking for their pot of gold at the end of the rainbow.
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I guess the governments don't like putting their money into research.
 
#20,125
@dam said:
Everyday it is seeming more obvious, that AI is going to beat humans to the ball at figuring out tinnitus (except perhaps Dr. Shore), hearing loss, basically everything. It's easy to go down the rabbit hole with AI. But the fact is, GPT4 is something else, and it's going to get better at an exponential rate.

For the majority of people who aren't familiar with the term A.G.I (Artificial General Intelligence), it is basically the benchmark to which an AI is on the same level as human intelligence or higher. The predicated time of achieving AGI is continuously being pushed forward.

The AI Revolution: The Road to Superintelligence

Regardless of tinnitus, this is a must read for everyone. This is what the future is shaping up to look like.

Once we can achieve AGI, intelligence is a cheap commodity that almost shares the same price as electricity. So you could simulate 100, 1,000, 10,000, 100,000, etc (scale indefinitely) top level researchers, that would quite easily solve every problem humanity has (tinnitus). AGI could potentially self-improve itself at an extremely fast pace. So then you could have 6 digit IQ simulated researchers and scientists.

I have more faith in that AI will be first, considering that hearing drugs are still years away.
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Yes, but also no. AI/AGI will only have as much intelligence as humans do to start out with. And even the smartest of us as humans have limited knowledge. We STILL do not understand even a tenth of what there is to know about the human brain. AI can scale up the research but they can only work with the possible data. And the possible data comes from the limited knowledge that we already have as human beings. In the end, even AI's knowledge will be limited.
 
#20,126
derpytia said:
Yes, but also no. AI/AGI will only have as much intelligence as humans do to start out with. And even the smartest of us as humans have limited knowledge. We STILL do not understand even a tenth of what there is to know about the human brain. AI can scale up the research but they can only work with the possible data. And the possible data comes from the limited knowledge that we already have as human beings. In the end, even AI's knowledge will be limited.
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Your points are valid, and I agree that at the outset, AI is indeed limited by the initial knowledge we input and teach it. However, the power of AI, particularly when it comes to AGI, lies in its capacity for exponential learning and self-improvement.

In contrast to human researchers who require years to study, learn, and develop new hypotheses, AGI can process and learn from vast amounts of data at a rate far beyond human capability. It's this capacity to ingest, analyse and draw connections across colossal amounts of data from various fields that could lead to discoveries we humans may not have made.

Moreover, AGI's ability to work tirelessly means that it can effectively operate a theoretically unlimited number of research 'man-hours.' This increases the probability of making significant discoveries or advancements. It's not just about utilizing our existing knowledge more effectively; it's about AI's potential to drive the acquisition of new knowledge at a pace and scale that humans can't match.

While it's true we don't fully understand the human brain or many other complex systems yet, AGI's data processing capabilities might lead to breakthroughs that bring us closer to that understanding. In other words, the limited knowledge of humans isn't a static ceiling for AI – it's a springboard.
 
#20,127
derpytia said:
Yes, but also no. AI/AGI will only have as much intelligence as humans do to start out with. And even the smartest of us as humans have limited knowledge. We STILL do not understand even a tenth of what there is to know about the human brain. AI can scale up the research but they can only work with the possible data. And the possible data comes from the limited knowledge that we already have as human beings. In the end, even AI's knowledge will be limited.
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I have to say I completely disagree with this though. "As much intelligence as humans do" is an extremely arbitrary statement. We as humans are very much biased to gauge knowledge and intelligence (two things that by the way are very often confused with each other) in relation to the human brain. A thing of which as you state, we know very little about.

A calculator surpassed human competence in the 1970s when it comes to math for example. We could easily see an explosion of extractable data coming from AI algorithms regarding neurological and other medicinal realms in the very near future in my opinion. A twenty first century calculator to map and spit out answers regarding human biology, if you will.
 
#20,128
Knowledge or intelligence?

AI being able to reason with less or more data?

The truth is no one really knows the impact AI will have on medical research. What I do think though is the MORE factual information the researchers can feed the AI, the better chance the AI will have of formulating cures.

Let's hope that scientists know more than we'd like to think they know, making the AI's job easier.
 
#20,129
Philip83 said:
A calculator surpassed human competence in the 1970s when it comes to math for example. We could easily see an explosion of extractable data coming from AI algorithms regarding neurological and other medicinal realms in the very near future in my opinion. A twenty first century calculator to map and spit out answers regarding human biology, if you will.
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Executing mathematical equations and comparing biochemical reactions within the human body are entirely unequal.

Anybody that thinks AI will be solving complex medical research within the next <100 years is living in an episode of Star Trek.
 

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