Frequency Therapeutics — Hearing Loss Regeneration

[Jim51042]

Research has found that providing more input can dampen tinnitus.

I think that everyone should be somewhat confident that synaptic and sensory regeneration will cure or significantly reduce noise induced tinnitus. The more open question is whether hyperacusis will remain after hearing restoration. I think that it probably will for the regrowth techniques of Frequency and probably Decibel.

The hair cells they make in a dish show that they have all the characteristics to function properly. They have long bundles, function electrically, and make the synapse components to connect to hair cells.

They are actively exploring the direct role of drugs on neurons.

This is the second best part of your conversation!!

Their work suggests that starting the regeneration process allows supporting cells and hair cells to restart the synapse formation process. If a person has all of their hair cells, this may not be the best option.

Humm this was my inference from reading all these papers. I still have an open question on whether or/and when I should undergo a Frequency procedure. My plan right now is to wait until at least Phase 1/2 is complete and to see what Decibel has achieved/doing trials of at that time. If they have something synaptic regrow focused trial I would lean toward that over a Frequency procedure but if it appears at that time there will be nothing else available into the distant future then beggars can't be choosers. Plus I honestly can't be sure I how many hair cells of mine don't work. Maybe that will be identifiable when Frequency completes their Phase 1/2.

 

[Foncky]

I'm in as soon as it starts... Even though it would be better to wait the last trial phase to get the "proper" dose.

 

[spingee]

I bet you will have to have at least moderate to severe hearing loss to be eliglibe in trial

 

[90's Kid]

I have some questions guys :
What if someone without dead hair cells uses their treatment ? Does it do nothing ?
What if it brings more hair cells than you already have ?
How will they process to check your number of dead hair cells ?

 

[Paulmanlike]

Will it be available for tinnitus sufferers with no measurable hearing loss?

 

[Foncky]

The clinical trial is probably about measurable hearing loss only so no.

I bet you will have to have at least moderate to severe hearing loss to be eliglibe in trial

I might be eligible with 60db loss over 4000Hz. But only severe to profound hearing loss will likely be eligible for the first phase.

 

[Jim51042]

The clinical trial is probably about measurable hearing loss only so no.

Depends on what measurable hearing loss is defined by. If the region is not defined by the 0-8 KHz you could have only 10 db of loss at 8 KHz and up to 60 dB in the higher region. In this scenario I would expect you be eligible for at least phase 3. If you only have 20 dB loss at the high frequencies even if you were eligible it might be smarter to wait for a synaptic cure then doing the trial. I really hope that we will have more information on this and other treatments by mid 2018 which make it easier to tailor the best clinic trial to your own personal medical state.

 

[RB2014]

The clinical trial is probably about measurable hearing loss only so no.


I might be eligible with 60db loss over 4000Hz. But only severe to profound hearing loss will likely be eligible for the first phase.

With a 60db loss over 4000hz I would not recommend you go for this trial. This hasnt been tested on a live human up to this point and no one knows what will happen. You could end up with H, you could lose some hearing, you could lose all your hearing, you could end up with unbearable T, or you could die(a little extreme, but possible). Really, the only people that should risk this are those looking at a Cochlear implant in the near future and/or maybe those that wouldnt mind having their auditory nerve cut. I'm much worst than you and even I am strongly considering whether to join or not. You can get by with really really bad hearing, hearing aides and reading lips.

I am still interested to see what the criteria will be, but I'm still thinking severe to profound. If they accept people with mild hearing loss, then it means they know this procedure won't have any ill effects because I just can't see them risking anyone with descent hearing on an untested procedure.

 

[90's Kid]

With a 60db loss over 4000hz I would not recommend you go for this trial. This hasnt been tested on a live human up to this point and no one knows what will happen. You could end up with H, you could lose some hearing, you could lose all your hearing, you could end up with unbearable T, or you could die(a little extreme, but possible). Really, the only people that should risk this are those looking at a Cochlear implant in the near future and/or maybe those that wouldnt mind having their auditory nerve cut. I'm much worst than you and even I am strongly considering whether to join or not. You can get by with really really bad hearing, hearing aides and reading lips.

I am still interested to see what the criteria will be, but I'm still thinking severe to profound. If they accept people with mild hearing loss, then it means they know this procedure won't have any ill effects because I just can't see them risking anyone with descent hearing on an untested procedure.

Trial will be only for the worst cases, then they can improve the treatment to focus on middle cases, and then more and more specific cases...

It will be interesting if someone doing the trial has hearing loss AND tinnitus to see what happens

 

[Foncky]

@RB2014 I'm not looking for recommendations
I have extreme H and a very loud, intrusive T. I'm looking for relief to get a life back and I'm kind of certain that new hair cells might help tremendously with all that in my case.

Obviously I wouldn't apply for the first stage, and they wouldn't let me anyway. But once the safety is documented, phase III could be wider and I'd be totally willing to apply. I don't really have a life currently, it's more like surviving. So I'm willing to take risks, that's what it will take to get better.

But yeah, it's obvious they will start with people considering cochlear implants, so not much to loose. Just like with Genvec. And we saw that Genvec made some people worse.

 

[Jim51042]

It will be interesting if someone doing the trial has hearing loss AND tinnitus to see what happens

Because they are correlated there is bound to be someone in the first Phase aka Phase 1/2 with tinnitus. So if this treatment improves hearing loss substantially we will know definitively whether hearing restoration reduces T. Still there will be some delay for the treatment to work (aka neuron regrow takes maybe weeks). I think the brain will adjust to the new signals and reduce tinnitus immediately but it may a couple day for the full effect to kick in.

 

[Paulmanlike]

Why am I so excited for this knowing one day I won't have ringing

 

[acufenero]

In my very, very humble opinion, I can't see a scenario where growing new hair cells in a ear which lost hundreds of hair cell can make things worse.

And we saw that Genvec made some people worse.

Can you provide more info on this? Just for curiosity.

 

[Foncky]

You will have to read the Genvec thread. Someone was in contact with a participant on Facebook. The guy said that his hearing was finally worse after the trial so it was another good reason for him to go for a cochlear implant, if I remember well. But Genvec didn't publish official results yet I think.

 

[90's Kid]

I'm so excited for 2018/2019 guys too see the result of this trial

 

[VRZ78]

The thing is that in order for this treatment to work you need a decent amount of supporting cells, and people with profound hearing loss might have lost them also (there is no way to know at the moment). So maybe they'll also open the trial to people with moderate hearing loss to make sure that the patients have the required amount of supporting cells.

 

[Foncky]

You're right.

The main obstacle could be to find enough people for those trials...

I'll re-post my question :

Nice find !

For instance he says :
"We used LY411575 to control differentiation of progenitors into hair cells in vitro. However, in the cochlear tissue we actually applied the opposite mechanism and generated more progenitor cells that the tissue would differentiate into hair cells. This is in contrast to LY411575, which only converts progenitor cells into hair cells. As a result, LY411575 will eliminate the pool of progenitor cells/supporting cells in the cochlea, which play an important role in its function, and reduces the possibility of future treatments if new hair cells die. However, if you do not have progenitor cells, neither approach will work."

Pardon my stupid question, but how do we know we still have progenitor cells ?

 

[RB2014]

@RB2014 I'm not looking for recommendations
I have extreme H and a very loud, intrusive T. I'm looking for relief to get a life back and I'm kind of certain that new hair cells might help tremendously with all that in my case.

Obviously I wouldn't apply for the first stage, and they wouldn't let me anyway. But once the safety is documented, phase III could be wider and I'd be totally willing to apply. I don't really have a life currently, it's more like surviving. So I'm willing to take risks, that's what it will take to get better.

But yeah, it's obvious they will start with people considering cochlear implants, so not much to loose. Just like with Genvec. And we saw that Genvec made some people worse.

I didnt realize you have extreme H. Agreed, you don't have much to lose. Neither do I. Maybe we will see each other in phase 2 or 3. Who knows.

Yes it was Uncle Jeff that ended up getting the cochlear implant in the end after having the procedure done.

Just my 2 cents Fonky... but if they are messing with dosages then this is something we probably want to stay away from. I know in the Testing for ATOH1 too much or too little of the gene therapy solution had negative effects. The dosage had to be just right. That could have been what happened with some of the people that got worst. We will know more once the results are released. It will be interesting to see what Frequency will end up testing. Hopefully they know the right dosage right off the bat with all of the additional testing they are doing.

If I go into the trial, I was some assurances that I have a good chance of getting my hearing back.

I am way more excited about this trial than the genvec trial though. Honestly, though the genvec trial looked pretty promising too with the animal data they had, but I think these guys have taken it a couple steps further.

 

[Aaron123]

I know in the Testing for ATOH1 too much or too little of the gene therapy solution had negative effects. The dosage had to be just right.

Given that results haven't been released, on what evidence are you basing this?

In my opinion they will target people with severe to profound hearing loss. I still say taking someone with a moderate loss, experimenting on them, and causing them to lose their hearing completely is not only life changing, but would be irresponsible.

I've written elsewhere that there are reasons why the criteria may not be as extreme for Frequency.

Honestly, though the genvec trial looked pretty promising too with the animal data they had,

The trial looked pretty good with the science that existed 5-6 years ago. It looks pretty grim now, though a recent paper in Cell Reports suggests reasons why some papers looking at ATOH1 find positive results and some don't.

 

[Foncky]

I am way more excited about this trial than the genvec trial though. Honestly, though the genvec trial looked pretty promising too with the animal data they had, but I think these guys have taken it a couple steps further.

For Genvec, didn't they have to laser drill a hole through the cochlea ?

The delivery alone was risky and less than ideal if I'm correct.

It was less promising than Frequency from the start anyway.

 

[RB2014]

Given that results haven't been released, on what evidence are you basing this?

You are right the results haven't been released. I was basing that statement on the animal trials and dosages that I had read from previous reports of CGF166 being injected in the cochlea of the animals they tested it on.

Yes, Fonky, Genvec laser drill a hole through the cochlea. Supposedly its safe and done all the time though.....

Agreed the delivery is less risky but we are still not sure what the procedure will do to a living adult human.

I've written elsewhere that there are reasons why the criteria may not be as extreme for Frequency.

We do know more now and I hope they relax the criteria as you have mentioned. I guess we will see what happens. Even though there are risks I believe my hearing chart is "close enough" to the genvec trial criteria.

 

[Reinier]

so it was another good reason for him to go for a cochlear implant

If the CLI worked as expected the GenVec treatment did not have damaging effects on other parts of the inner ear.

 

[RODRIGO]

Hello Rodrigo,

I hope this message finds you well.

Last week, Frequency Therapeutics announced the closing of a $32 million Series A financing. The funding round, led by CoBro Ventures, also included Morningside Ventures, Emigrant Capital Corp., Korean Investment Partnership, Alexandria Real Estate Equities and other U.S. and international investors.

With this funding round, Frequency will look to the clinical development of a first-in-class hearing restoration treatment based on their proprietary Progenitor Cell Activation (PCA™) platform.
We wanted to share with you the great coverage in the Boston Globe last week around this announcement. In addition, please feel free to visit our website to view the original press release for more information.
Thank You.
David Lucchino
President, CEO and Co-founder
Frequency Therapeutics

 

[RB2014]

I checked out the article on the Boston Globe. Its interesting that David Lucchino has hearing loss too from too many U2 concerts. I wonder if he ends up using himself as a test subject. It looks like from the comments section that there are lots of people willing to be guinea pigs for this procedure. Fonky, we could have lots of competition.

"There's 1.1 billion people around the world who are at risk or have hearing loss. We've figured out a way to biologically hot-wire the sensory hair cells in a very natural way to get the ear to heal itself."

All I can say is Wow.

 

[Paulmanlike]

The hearing aid companies can kiss goodbye to their profits with over priced aids, oooo hearing loss will soon be something of the past. Love positivity and hope.

 

[Rubenslash]

The hearing aid companies can kiss goodbye to their profits with over priced aids, oooo hearing loss will soon be something of the past. Love positivity and hope.

I am wondering how these companies will handle this, they will have to drastically change their business model if these treatments will be successful in order to stay relevant.

 

[Reinier]

I wonder if you can use hearing aids for conductive hearing loss.
Often conductive hearing loss is in the lower frequencies. Not so ideal for hearing aids.

Also, perhaps there is a way to find out if hearing aids companies are getting nervous.
Could be an indication that the biological solution is getting serious.

 

[Paulmanlike]

Hope so, its the tinnitus cure I'm holding on for. If they can do that regenerating hair cells and reversing hearing loss - happy days.

 

[RonnieCarzatto]

I would personally harass the Nobel committee to give these people the Peace Prize

 

[Paulmanlike]

I remember telling Dr Wilden how good he was when reading on LLLT years ago, thinking I owed my life to him, however I found out painfully it's a load of bollocks.