Frequency Therapeutics — Hearing Loss Regeneration

[Ed209]

And, yes, you have, if not directly, numerous times said that we don´t know what it will do with tinnitus (then of course tinnitus from SNHL) and so on. You talk about maladaptive something....

That's a different question entirely, and something else to ponder. I'm only probing these issues because I've always had a deep fascination with neuroscience, quantum mechanics, and the universe. I've got books on all of these things, and subscribe to New Scientist magazine. This is why I'm asking; I thought somebody might have more relevant info on it.

A totally unrelated case, that I recall, is when a bionic eye was successfully fitted onto a man's optic nerve, but his brain didn't know what to do with the information it was receiving and it freaked him out. He could see, but it wasn't correctly decoded in his brain.

I remember reading an article/s, back when I was relentlessly researching all things to do with our auditory system, and one thing that stuck in my mind (when it came to hair cell regeneration) was whether regenerated hair cells would connect up to the brain or not. Could the hair cells regenerate but remain dormant, for example? Or could they send a signal that's different to our other hair cells? Maybe they will work perfectly. I don't know, and that's why I asked if anyone else had any info on it from Frequency Therapeutics, or any of the other companies who are studying it.

I'm guessing you think I posted it because you believe I want it to fail or something? Some of the replies seem rather defensive for such an innocent question.

 

[Tinker Bell]

That's a different question entirely, and something else to ponder. I'm only probing these issues because I've always had a deep fascination with neuroscience, quantum mechanics, and the universe. I've got books on all of these things, and subscribe to New Scientist magazine. This is why I'm asking; I thought somebody might have more relevant info on it.

A totally unrelated case, that I recall, is when a bionic eye was successfully fitted onto a man's optic nerve, but his brain didn't know what to do with the information it was receiving and it freaked him out. He could see, but it wasn't correctly decoded in his brain.

I remember reading an article/s, back when I was relentlessly researching all things to do with our auditory system, and one thing that stuck in my mind (when it came to hair cell regeneration) was whether regenerated hair cells would connect up to the brain or not. Could the hair cells regenerate but remain dormant, for example? Or could they send a signal that's different to our other hair cells? Maybe they will work perfectly. I don't know, and that's why I asked if anyone else had any info on it from Frequency Therapeutics, or any of the other companies who are studying it.

I'm guessing you think I posted it because you believe I want it to fail or something? Some of the replies seem rather defensive for such an innocent question.

There are other examples of eyes providing input but the brain lacking the ability to interrupt the information. I was born with an eye condition that required surgery. My brain relied heavily on my better eye, and as a result its connection to the bad eye weakened. Even when we correct the vision in my bad eye with glasses, the damage is done. My brain lacks the ability to interrupt what my eye correctly sends; there's a disconnect that cannot be fixed.

Hopefully the brain has more plasticity when it comes to our hearing.

 

[grate_biff]

I'm guessing you think I posted it because you believe I want it to fail or something? Some of the replies seem rather defensive for such an innocent question.

By no means, no. But all we can do right now is to discuss what would most logically happen, when auditory input is restored to our brain. I have an opinion, which, I guess is slightly optimistic.
In my view, you have a more sceptic opinion of things, which is fine!
Also related to how soon, if successful, it will be available to us!

Soon, hopefully, we will have our questions answered and the main one being, what will this do with our tinnitus and hyperacusis.
In light of that, some will stand as naively optimistic opportunists and some will stand as cavil over-complicators. Some in between.
Not to put you or any one else in any category.

I feel, I can´t afford this not to be successful. Dangerous, maybe. But that's where I´m coming from and that color my views. Hope is my dope!

 

[katri]

That's a different question entirely, and something else to ponder. I'm only probing these issues because I've always had a deep fascination with neuroscience, quantum mechanics, and the universe. I've got books on all of these things, and subscribe to New Scientist magazine. This is why I'm asking; I thought somebody might have more relevant info on it.

A totally unrelated case, that I recall, is when a bionic eye was successfully fitted onto a man's optic nerve, but his brain didn't know what to do with the information it was receiving and it freaked him out. He could see, but it wasn't correctly decoded in his brain.

I remember reading an article/s, back when I was relentlessly researching all things to do with our auditory system, and one thing that stuck in my mind (when it came to hair cell regeneration) was whether regenerated hair cells would connect up to the brain or not. Could the hair cells regenerate but remain dormant, for example? Or could they send a signal that's different to our other hair cells? Maybe they will work perfectly. I don't know, and that's why I asked if anyone else had any info on it from Frequency Therapeutics, or any of the other companies who are studying it.

I'm guessing you think I posted it because you believe I want it to fail or something? Some of the replies seem rather defensive for such an innocent question.

You have tons of good points....but I think a bionic eye is completely unrelated to naturally inducing our bodies healing process. I'll take slightly distorted hearing, if that's what you mean. Also we are all encouraged by progress Novartis has had with regenerating hearing. We can assume that frequency will work better.

 

[Leoglobe]

@Ed209 I think that is a good question but we don't know exactly how it will work.

In the 24min video that I think you watched, they say that they can regrow the cells with the right shape and right spot which is crucial in the cochlea.

PCA sounds much better than gene therapy for this by the way because it imitates a natural process whereas gene therapy can create easily hair cells but too many of them and disorganized. I personally have great hopes for Frequency Therapeutics, kind of hope I never had before for any trials because I truly believe in progenitor cell activation, sounds much more accurate and precise than gene therapy.

To do gene therapy well the researchers should know all the genes of the cochlea and this would take forever. A good cell in the right shape and right spot should connect easily to an auditory neuron, the brain is supposed to do synapses that's the all concept of plasticity and Frequency Therapeutics said they can make those synapses.

PCA can be done on other parts of the body and indeed Frequency Therapeutics have other projects in this regard but the fact that they chose hearing regeneration instead of another part of the body first, makes me think that they are pretty confident with what they are doing. Honestly they could have chosen another part of the body first, get good investments from this and then look at the hearing regeneration. That could have been wiser from an investment point of view but instead they chose hearing regeneration first and that is an interesting fact from a strategic point of view, I think they are quite confident with what they are doing and hungry for this market because if they succeed they will be known worldwide.

 

[GregCA]

It's not as simple as that. Do we know if the new hair cells connect to the brain properly? That's all I'm asking. I figured someone might have some information on it, but I didn't expect this response.

As far as I know, there is some evidence that a new hair cell appearing results in some "pull" from a nerve cell nearby to create a synapse, provided the "pull" doesn't require too much distance to cover. What I read is that we weren't sure why this happens, but it seems to happen.

We know there is some retraction that happens in time once the hair cells die, but that process is relatively slow. I posted an article a while ago about a guy who got a cochlear implant after decades of losing hearing, and somehow the "connection" still worked from the cochlea to the brain, so the electrical signal from the CI electrode did make its way to the hearing nerve somehow.

 

[JohnAdams]

I'm only probing these issues because I've always had a deep fascination with neuroscience, quantum mechanics, and the universe.

Doug. Tinnitus has jack squat to do with quantum physics. Stop muddying the waters with your ridiculous naysaying and ignorant speculation. Jeez louise man. I'm sorry for lashing out at you but still. Can you not balance your profound pessimism with some logic from time to time?

AM-101 Keyzilen failed because that theory was wrong. The other theory is restoring hearing will help/cure shitnitus so just stop, stop with your naysaying nonsensical irrational arguments against hair cell regeneration. We get it, you don't believe this is the answer. We get it bruh.

 

[d'Wooluf]

I've never asked this question before? I was just curious if anyone had any further information about it from Frequency Therapeutics' point of view.

I wondered how the brain might handle the new sensory stimuli (if the cells send a viable signal, that is), as it's surely an important part of the equation? It was a legitimate question.

It's a legitimate question. It's just that no-one knows the answer to it. It probably depends on how long the hearing's been lost and how old you are. Frequency Therapeutics cannot know everything about how the brain reacts to the regeneration of hair cells. They are waiting to find out just like everybody else.

Edit: If the brain has not been receiving auditory input at certain frequencies for a long time, it's quite likely that it has found another use for that part of the brain that used to process those frequencies. The brain is also quite plastic. It can restore a lot of functionality after a stroke destroys brain tissue for instance by re-routing signals and re-purposing other parts of the brain. I think that your hearing would continue to improve even months after getting the injection.

 

[d'Wooluf]

I'm guessing you think I posted it because you believe I want it to fail or something? Some of the replies seem rather defensive for such an innocent question.

Yes. There's a certain psychology at work.

 

[JohnAdams]

It's not as simple as that. Do we know if the new hair cells connect to the brain properly? That's all I'm asking. I figured someone might have some information on it, but I didn't expect this response.

@grate_biff did not post anything unexpected. His comment was logical and rational. Why would you describe his comment as "unexpected"? That's really silly to me.
Can you engage in a mature debate?

 

[d'Wooluf]

Do we know if the new hair cells connect to the brain properly?

We do know that Frequency Therapeutics believe that new neurons are formed to connect the hair cell to the neural pathways to the brain. So the on-ramp to the freeway will be there at least.

 

[Ed209]

@grate_biff did not post anything unexpected. His comment was logical and rational. Why would you describe his comment as "unexpected"? That's really silly to me.
Can you engage in a mature debate?

Ok John, I've been really patient with you, but you are taking liberties now. At no point have I insulted anyone, unlike you when you were giving me abuse (which I let slide), so calm down. I asked a simple question and the first couple of replies I got were very odd and more suggestive that I'm trying to piss on your parade or something. It's starting to get a bit ridiculous now if I'm being honest.

I thought this was a forum for debating stuff? However, just lately things are becoming unrecognisable to the point that I'm not sure why I'm even here anymore.

 

[john paul]

I read about another discovery scientists have made recently in that they have identified the protein or channel in the ear responsible for converting sound into the electrical signal sent to brain. Also new deployment technology using magnets to get stuff to pass into the ear. I'm certain that scientists will be able to mend the human ear soon.

 

[JohnAdams]

It's not as simple as that. Do we know if the new hair cells connect to the brain properly?

I believe we already know the answer to this question. Preclinical tests in rodents showed that their hearing was restored from hair cell regeneration. That means that the hair cells made the correct connections.

 

[JohnAdams]

I don't wish to fight, but all I'm trying to do is make a case that hair cell regeneration has a great chance of alleviating tinnitus. I have extensively researched as much available information that I can about this technology, and ear biology and I try to stay grounded in facts. It is then somewhat aggravating when you reply to healthy speculation with non-factual retorts like this.

Unfortunately, back in reality we still have no idea about it's safety profile

When you say, "unfortunately back in reality," you have just insinuated that I'm not living in reality. It's an underhanded and subtle insult. And it's offensive man. This sort of quip is originally why I got so upset with you in the first place.

And contrary to your insinuation that I'm somehow not living in reality and that we have no idea about the drugs safety profile, we do in fact know from the first trial.

"This goal was achieved by showing that FX-322 was well tolerated with no drug related adverse events reported."

https://finance.yahoo.com/news/frequency-therapeutics-first-human-safety-130000297.html​

A trial of 24 people (I think 8 or maybe 12 who will actually take the drug)

24 subjects.

16 got the drug, 8 placebo.

https://clinicaltrials.gov/ct2/show/NCT03616223

and it will take a few years to find out.

The trials seem to be lasting on average 3-4 months.

A totally unrelated case, that I recall, is when a bionic eye was successfully fitted onto a man's optic nerve, but his brain didn't know what to do with the information it was receiving and it freaked him out. He could see, but it wasn't correctly decoded in his brain.

I couldn't find any reference to this bionic eye experiment where it freaked out the patient. I'm very interested in this and would appreciate a link if possible.

I did however find this about a bionic eye.

"Mr Flynn said he was "delighted" with the implant and hoped in time it would improve his vision sufficiently to help him with day-to-day tasks like gardening and shopping."

BBC News - Bionic eye world first
​

Please I'm asking you. If you're going to tell people they're wrong about why it will or won't do something, please take due diligence to research the facts, and post sources to your claims. That's all I'm asking. I don't want to fight with you.

And lastly, I'm putting the question of whether regenerating hair cells is effective in restoring hearing to rest.

"The goal of this landmark First-in-Human study was to prove the safety and tolerability of FX-322 at a dose that has been effective in restoring hearing in animals,"

https://finance.yahoo.com/news/frequency-therapeutics-first-human-safety-130000297.html​

 

[Ed209]

@JohnAdams, I've learned that it's pretty much impossible to talk to you as you either fly off the rails, or say things that are really out-there (in my opinion of course). Hence the "back in reality" comment which is not personal at all, but just an expression.

I can't play the quoting game as your insults were deleted, but I've repeatedly said that I am fine with you and didn't even take your abuse personally. I said you're a decent guy who is just feeling frustrated. I defended you.

You are quoting things from MPP back when I hadn't looked at the trial design. However, as you were posting stuff about FX-322 in every thread all over the forum, I took a quick look (at the time) to see how many participants there were. And you're right, there are 16 being given FX-322 and 8 being given a placebo. I don't see how that's relevant in this discussion though?

I said I would leave you alone to post here and I meant it. I just wanted to ask a question and it's descended into chaos again.

PS: the guy with the bionic eyes was on a documentary I saw; I think it could have been BBC Horizon, but it was years ago so I can't remember. I remember they talked about him lying down on the back seat of a car when being driven, because his brain was perceiving everything as being dangerous. At this point there were neurologists talking about how the brain has to decode the information it is being given, and if this process goes wrong or is misinterpreted, it can lead to other problems.

I'm aware of the preclinical mice trial which is why I asked the question I did. It's not like we can ask the mice how they "hear" their restored hearing. Obviously, a cochlear implant is nowhere near the same thing as regenerating hair cells, but the brain doesn't hear the same with one of those. This just got me thinking if the brain would interpret regenerated hair cells the same as the ones we're born with.

I don't think we can know the answer to this until we hear from people who have been given FX-322.

Anyway, sorry for disrupting the thread. I'll make sure to stay away from now on.

 

[Pero1234]

I don't wish to fight, but all I'm trying to do is make a case that hair cell regeneration has a great chance of alleviating tinnitus. I have extensively researched as much available information that I can about this technology, and ear biology and I try to stay grounded in facts. It is then somewhat aggravating when you reply to healthy speculation with non-factual retorts like this.


When you say, "unfortunately back in reality," you have just insinuated that I'm not living in reality. It's an underhanded and subtle insult. And it's offensive man. This sort of quip is originally why I got so upset with you in the first place.

And contrary to your insinuation that I'm somehow not living in reality and that we have no idea about the drugs safety profile, we do in fact know from the first trial.

"This goal was achieved by showing that FX-322 was well tolerated with no drug related adverse events reported."

https://finance.yahoo.com/news/frequency-therapeutics-first-human-safety-130000297.html​

24 subjects.

16 got the drug, 8 placebo.

https://clinicaltrials.gov/ct2/show/NCT03616223


The trials seem to be lasting on average 3-4 months.


I couldn't find any reference to this bionic eye experiment where it freaked out the patient. I'm very interested in this and would appreciate a link if possible.

I did however find this about a bionic eye.

"Mr Flynn said he was "delighted" with the implant and hoped in time it would improve his vision sufficiently to help him with day-to-day tasks like gardening and shopping."

BBC News - Bionic eye world first
​

Please I'm asking you. If you're going to tell people they're wrong about why it will or won't do something, please take due diligence to research the facts, and post sources to your claims. That's all I'm asking. I don't want to fight with you.

And lastly, I'm putting the question of whether regenerating hair cells is effective in restoring hearing to rest.

"The goal of this landmark First-in-Human study was to prove the safety and tolerability of FX-322 at a dose that has been effective in restoring hearing in animals,"

https://finance.yahoo.com/news/frequency-therapeutics-first-human-safety-130000297.html​

JohnAdams, what everyone is trying to say is just: take it easy. Most of us are as excited about Frequency Therapeutics as you are. I for one believe it has the potential to literally change the lives of millions of people.

All we ask of you is to join us while we eagerly await new information from the trial.

We look forward to discussing what comes out. But for now... I believe everything that needed to be said is said. We just have to be patient.

There are still many unknowns and to claim the cure to hearing loss AND tinnitus has arrived is a bit too soon... That is not negativity or skepticism... it's healthy common sense.

Yes, the mice could hear something again... but for all we know they just registered garbled noise. The fluffy little buggers can't describe it to us...

Let's just count ourselves lucky - if one can ever feel that way with tinnitus / hearing loss - to be alive during this most exciting time. A time where there's hope. Let's all be patient with each other's opinions... stay constructive, forgiving and count down to the end of December.

We're all in this together.

Instead of counting down to the new year at loud parties... let's all count down to Frequency Therapeutics' next press release this year.

10-9-8-7...

 

[JohnAdams]

to claim the cure to hearing loss AND tinnitus has arrived is a bit too soon...

I agree. Who's claiming that the cure to hearing loss and tinnitus has arrived?

 

[Jason37]

I would like to clear things up pertaining to the timeline.

I was in the FX-322 trial before bowing out after my physical and did not receive the injection due to some fears and risks brought to my attention. I was the fifth candidate back in August and I have the schedule for the patients.

There were 4 return visits after injection... 2 weeks, 30 days, 60 and 90 days. Each patient was scheduled at their leisure. After speaking to Dr. Rosenblum (running study for Frequency Therapeutics in San Antonio) he does think it will work from what he's seen.

If I remember correctly he said this phase 1/2 will be wrapped up by spring after all the return visits of the subjects.

I do not know if I will regret not going through with it and taking the risk.

Right now I kind of regret it that I didn't follow through, but I didn't want that half dose to only grow my hair cells half way... I dunno.

 

[Jason37]

Am I allowed to post some of the risks and/or timeline from the paper I signed, or would that get me in hot water or not be good?

 

[Johan_L]

I would like to clear things up pertaining to the timeline.

I was in the FX-322 trial before bowing out after my physical and did not receive the injection due to some fears and risks brought to my attention. I was the fifth candidate back in August and I have the schedule for the patients.

What risks were mentioned?

There were 4 return visits after injection... 2 weeks, 30 days, 60 and 90 days. Each patient was scheduled at their leisure.

If they follow up 90 days after injection, and the final injection was in early October, the trial cannot complete until early Jan. So I guess it's very likely that we will have to wait until then even if December might have been the original plan...

P.S. Is this you? This guy also bowed out... https://www.reddit.com/user/NoMoreTPlease?

 

[Johan_L]

Am I allowed to post some of the risks and/or timeline from the paper I signed, or would that get me in hot water or not be good?

I doubt there is risk. Timeline is basically public:

https://www.marketwatch.com/press-r...-candidate-for-hearing-restoration-2018-10-04
"Patients received either an injection of FX-322 or a placebo in one ear with an initial follow up visit after two weeks and will continue to be monitored for the following three months."​

 

[Jason37]

Yes it is me.

Hearing loss was a possible risk from injection and altering the mechanical parts of your inner ear might cause hearing loss as well. Also there is a bit in there about dosage.

They are making an educated guess right now on what will be enough. The hair cells could start to grow, and stop and leave you without any more sets of progenitor cells if they get it right later. Shit... Now that I'm talking about it I missed my chance. F@&$.

 

[Fabrikat]

Hearing loss was a possible risk from injection and altering the mechanical parts of your inner ear might cause hearing loss as well.

Do you mean the needle actually hitting the fine bones of the middle ear and damaging them or that the chemical could actually alter the bones' functioning?

Could they include you again for latter phases considering they found you an acceptable candidate for the first ones?

 

[Johan_L]

Shit... Now that I'm talking about it I missed my chance. F@&$.

Man... a lot of people here would have been glad to have an "insider" in the trial. You can see the looooooong discussions here .

It's not as if you blew your chances forever. If it works you will get it sooner or later. Anything that makes you think you would not be admitted in the Phase 2 next spring? If you were admitted to Phase 1/2 then next time should not be a problem! (They will need even more people!)

 

[Striveon]

Yes it is me.

Hearing loss was a possible risk from injection and altering the mechanical parts of your inner ear might cause hearing loss as well. Also there is a bit in there about dosage.

They are making an educated guess right now on what will be enough. The hair cells could start to grow, and stop and leave you without any more sets of progenitor cells if they get it right later. Shit... Now that I'm talking about it I missed my chance. F@&$.

It's a tough decision to make. We don't know exactly what will happen and will not want to regret it and have to deal with worse tinnitus and hearing loss. I was thinking of going till the last trial, but then again how long would it take to be released after the last trial... it sucks because we might have the cure, but then I don't want to risk it but don't want to wait another 5 years. Hopefully there's a fast track or something we can do to speed up the process.

 

[Leoglobe]

@Jason37 scary the risk of substantial hearing loss and it is what they are supposed to fix. I am so confused.

 

[Ed209]

Yes it is me.

Hearing loss was a possible risk from injection and altering the mechanical parts of your inner ear might cause hearing loss as well. Also there is a bit in there about dosage.

They are making an educated guess right now on what will be enough. The hair cells could start to grow, and stop and leave you without any more sets of progenitor cells if they get it right later. Shit... Now that I'm talking about it I missed my chance. F@&$.

Don't beat yourself up, man. You made a decision at the time that was a difficult judgement call to make, and you still don't know yet what the outcome will be for the people who have participated.

If it turns out to be safe and efficacious, then you will have the option, one day, to have it delivered into your cochlea safely and with the optimum dosage.

There is no correct decision with stuff like this. I had to make an incredibly hard judgement call when I was 19; I was given the option of major surgery for another condition, and I probably made the wrong choice. Yet if I didn't take it, I can guarantee I'd be living a life of regret now, wishing that I did. With decisions like these you simply cannot win.

Don't let any regrets eat you up. You made the right decision, because at the time you had weighed up the pros and cons and ultimately made a choice based on them. Stand by your convictions and don't let any doubts concern you at this point. We cannot change the path we're on.

 

[Jason37]

I think the are mostly talking about tympanic injection and just the fact that they are changing the physical structure of the inner ear I guess. That may cause more hearing problems.

 

[Jason37]

Don't beat yourself up, man. You made a decision at the time that was a difficult judgement call to make, and you still don't know yet what the outcome will be for the people who have participated.

If it turns out to be safe and efficacious, then you will have the option, one day, to have it delivered into your cochlea safely and with the optimum dosage.

There is no correct decision with stuff like this. I had to make an incredibly hard judgement call when I was 19; I was given the option of major surgery for another condition, and I probably made the wrong choice. Yet if I didn't take it, I can guarantee I'd be living a life of regret now, wishing that I did. With decisions like these you simply cannot win.

Don't let any regrets eat you up. You made the right decision, because at the time you had weighed up the pros and cons and ultimately made a choice based on them. Stand by your convictions and don't let any doubts concern you at this point. We cannot change the path we're on.

Or I had a good chance of getting the half dose or placebo and that is why I ultimately decided not to. That would suck to spend 4 grand traveling back and forth and only get a hole in your ear.