Frequency Therapeutics — Hearing Loss Regeneration

[JohnAdams]

nieqorgvneqroneroneqogneroneronerong!

https://www.frequencytx.com/news-events/news-events-press-release-07-23-2019.php

 

[Reinier]

https://www.frequencytx.com/news-events/news-events-press-release-07-23-2019.php

So this is another 62 million dollar? It was only one week ago that they made this deal with Astellas.

I haven't got a clue when it comes to things finance, but this is good news, is it not?

 

[JohnAdams]

https://www.frequencytx.com/news-events/news-events-press-release-07-23-2019.php

So this is another 62 million dollar? It was only one week ago that they made this deal with Astellas.

I haven't got a clue when it comes to things finance, but this is good news, is it not?

Yes. All signs point to them having a real winner on their hands.

 

[Ivkopivko]

Yes. All signs point to them having a real winner on their hands.

From such a small trial with non-publicly released results/outcome? I obviously don't understand what's behind but doesn't make a sense as they completed phase of trial with such a low number of participants. (Of course I hope I'm wrong and they and their investors that might be acknowledged with results already sees another breakthrough).

 

[JohnAdams]

From such a small trial with non-publicly released results/outcome? I obviously don't understand what's behind but doesn't make a sense as they completed phase of trial with such a low number of participants. (Of course I hope I'm wrong and they and their investors that might be acknowledged with results already sees another breakthrough).

They also have robust in vitro and in vivo evidence that the drug regrows the hair cells and that they reconnect and restore hearing function.

 

[Reinier]

From such a small trial with non-publicly released results/outcome? I obviously don't understand what's behind but doesn't make a sense as they completed phase of trial with such a low number of participants. (Of course I hope I'm wrong and they and their investors that might be acknowledged with results already sees another breakthrough).

But I think there is more to it.
Don't forget that investors will be able to make more informed decisions to invest or not to invest. Investors will try to find information to make the investment as low risk as is possible. I assume FT will give investors more information than the information they share with non investors.

 

[Mathieulh]

The technique to deliver that gene therapy is absurd. They surgically remove the eardrum, drill a hole in the cochlea with a laser and then inject the reprogrammed virus into the hole in the cochlea and then reattach the ear drum. Then the virus injects the stem cells in the cochlea with ATOH1.

Well, it'd still make sense if you were totally deaf, otherwise I wouldn't risk such an invasive procedure xD

 

[85dB T]

They also have robust in vitro and in vivo evidence that the drug regrows the hair cells and that they reconnect and restore hearing function.

@JohnAdams I forgot your opinion. What are the chances that hair cell regrowth will reduce or eliminate tinnitus? Of course we'll wait and see, am just curious.

I pray this miracle will happen. Don't we all.

 

[zhiyuan]

Does anyone know if the loss of hair cells cause damage to the supporting cells?

FX-322 use supporting cells but if someone's supporting cells get hurt, it means nonsense?

And it seems like there are different types of hair cells since they sense different frequencies, so FX-322 could regenerate various types of hair cells?

 

[ChrisBoyMonkey]

Does anyone know if the loss of hair cells cause damage to the supporting cells?

FX-322 use supporting cells but if someone's supporting cells get hurt, it means nonsense?

And it seems like there are different types of hair cells since they sense different frequencies, so FX-322 could regenerate various types of hair cells?

I don't think the supporting cells would get hurt from cochlear damage like sound, as they do not react to it like hair cells do. It's like skin cells being able to be damaged by those levels of sound. And yes, those cells should be able to restore any frequency so long as they are hair cells.

Perhaps that's how they came up with their name...

 

[Mathieulh]

I don't think the supporting cells would get hurt from cochlear damage like sound, as they do not react to it like hair cells do. It's like skin cells being able to be damaged by those levels of sound. And yes, those cells should be able to restore any frequency so long as they are hair cells.

Perhaps that's how they came up with their name...

They can still get damaged from pathogens or ototoxic medications though. Sound however indeed wouldn't damage those.

 

[PolishSoldier87]

I wonder if FX-322 doesn't damage the order of the hair cells. Playing with notch signaling can lead to unexpected proliferation of hair cells. Anyone know something about this?

B - acceptable? What do you think?

A - No treatment
B - Atoh1 over-expression
C - g-secretase inhibitor in the Notch signal pathway
D - Atoh1 over-expression + g-secretase inhibitor

 

[Fabrikat]

They can still get damaged from pathogens or ototoxic medications though. Sound however indeed wouldn't damage those.

So do you think that FX-322 would not be able to regrow hair cells, where they have been damaged by virus or ototoxic medications?

 

[streeter1985]

Does anyone know if the loss of hair cells cause damage to the supporting cells?

FX-322 use supporting cells but if someone's supporting cells get hurt, it means nonsense?

And it seems like there are different types of hair cells since they sense different frequencies, so FX-322 could regenerate various types of hair cells?

I already mentioned the hyperlink, if you are interested in it you can read it: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637947/

In summary if you have severe to profound hearing loss there could be a flat epithelium in the cochlea. The huge damage forms scars and can also eliminate Pillar and Deiter cells which in my opinion are very important concerning the right alignment of the new grown hair cells. It seems that there is a lack of supporting cells in that flat epithelium. So we can only hope that their approach also eliminates that problem. Only time can tell... if the sequence allows your body to automatically differentiate between the location of damage and the formation between Pillar and Deiter cells and the right position for regrowing hair cells everything is fine

The flat epithelium only takes 1 week to be formed from your body after damage. If humans would be able to regrow hair cells (by nature) right after damage maybe that process would have been stopped... but thats just an idea.

Well that's how I understand that manuscript...

 

[Mathieulh]

So do you think that FX-322 would not be able to regrow hair cells, where they have been damaged by virus or ototoxic medications?

I don't know, it would take clinical trials to find out.

 

[PolishSoldier87]

So do you think that FX-322 would not be able to regrow hair cells, where they have been damaged by virus or ototoxic medications?

It's probable that they can be regrown, unless pillar and phalangeal cells are destroyed.

On the other hand I found a view where proliferation of supporting cells also happens.

 

[zhiyuan]

The flat epithelium only takes 1 week to be formed from your body after damage.

That's sad. So when FX-322 comes, we all have some flat epithelium that may decrease the effect.

 

[zhiyuan]

Here is the publication from Frequency Therapeutics:

http://dx.doi.org/10.1016/j.celrep.2017.01.066.

I just had a quick read and think the paper says they can expand the number of positive supporting cells. So maybe even if you have some injury to your supporting cells, the drug can still work.

 

[JohnAdams]

I forgot your opinion. What are the chances that hair cell regrowth will reduce or eliminate tinnitus?

Well, if the loss of hair cells is what has caused your tinnitus then I think it will help. If there is damage to nerves in other parts of the system that is causing hyperactivity then I don't see how this could work unless there is some kind of healing cascade effect.

 

[streeter1985]

That's sad. So when FX-322 comes, we all have some flat epithelium that may decrease the effect.

That depends on the individual situation of the cochlea after the damage - not everyone has severe to profound hearing loss. We have to wait until we know more and get some data from the trial. Maybe the power of the human body itself can solve some problems when FX-322 starts the sequence in the supporting cells like the miracle that nerves connect to the regrown hair cells etc. We also don't know anything about the quality (hearing) of regrown hair cells. I think the flat epithelium is only mentioned in connection with severe to profound hearing loss.

My personal opinion is that we are allowed to put hope into this approach. The idea behind FX-322 is great and the investments and co-operations also look very very promising.

 

[Daniel Lion]

That depends on the individual situation of the cochlea after the damage - not everyone has severe to profound hearing loss. We have to wait until we know more and get some data from the trial. Maybe the power of the human body itself can solve some problems when FX-322 starts the sequence in the supporting cells like the miracle that nerves connect to the regrown hair cells etc. We also don't know anything about the quality (hearing) of regrown hair cells. I think the flat epithelium is only mentioned in connection with severe to profound hearing loss.

My personal opinion is that we are allowed to put hope into this approach. The idea behind FX-322 is great and the investments and co-operations also look very very promising.

"allowed to put hope into this approach"

Amen to that...

Lots of hope and faith for better days, and better hearing.

Speed it up Frequency Therapeutics, bring it on, you got your cash...
Let's get the next trial started...

Sincerely, Daniel

 

[Enclave]

It's probable that they can be regrown, unless pillar and phalangeal cells are destroyed.
View attachment 31127

On the other hand I found a view where proliferation of supporting cells also happens.
View attachment 31128

In the 2nd diagram, what year was this created? Where is the literature you pulled this from?

I'm curious, did the verbiage mention what happens to the Tunnel of Corti between B and C in this diagram?

 

[Chriscom]

Have we got any evidence that restoring hearing will reduce tinnitus? Why then hearing aids don't help?

Hearing aids apparently help reduce tinnitus in some people, judging from what I've read around the web and heard from my audiologist and ENT.

 

[BrStan@]

Hearing aids apparently help reduce tinnitus in some people, judging from what I've read around the web and heard from my audiologist and ENT.

Hearing aids reduce tinnitus by acting like maskers.

 

[ChrisBoyMonkey]

Hearing aids reduce tinnitus by acting like maskers.

I have a coworker whose use of hearing aids stopped his tinnitus, even when he's not using them.

 

[Daniel Lion]

I have a coworker whose use of hearing aids stopped his tinnitus, even when he's not using them.

That's amazing.
First I ever heard of that.
Maybe that could happen for a few of us... wouldn't that be a miracle.

Take care Monkey.

 

[85dB T]

I have a coworker whose use of hearing aids stopped his tinnitus, even when he's not using them.

Were the hearing aids simply providing amplification or were they programmed a certain way to help tinnitus? (supposedly).

Instead of purchasing $3000 to $6000 hearing aids (prescribed by audiologist), I've been told many people are buying amplifiers like these at Bass Pro Shop for $150:

https://www.basspro.com/shop/en/gam...&pageView:grid&minPrice:&maxPrice:&pageSize:&

 

[Chriscom]

I have a coworker whose use of hearing aids stopped his tinnitus, even when he's not using them.

I don't want to claim more knowledge than I have, since I'm new to all this. But this doesn't surprise me.

Part of the reduction in tinnitus as others have stated is the result of masking and distraction. You're hearing things through that ear or ears that weren't heard before, so the brain is busy processing that and it pushes tinnitus to the background.

But based on what I've read, the evidence suggests it can also reduce tinnitus because now that sound is getting piped in again, the brain isn't sending the compensatory transmissions that started when the ear got shut down in the first place.

Because everyone's ears and brains are different there sure doesn't seem to be any way to predict if and when this will happen to an individual, but this is not the only time I've seen a report like this.

 

[JohnAdams]

the brain isn't sending the compensatory transmissions that started when the ear got shut down in the first place.

Are you sure that's what's happening?

everyone's ears and brains are different

they are?

 

[Mr Mister]

I wonder if FX-322 doesn't damage the order of the hair cells. Playing with notch signaling can lead to unexpected proliferation of hair cells. Anyone know something about this?

B - acceptable? What do you think?

View attachment 31125
View attachment 31126

A - No treatment
B - Atoh1 over-expression
C - g-secretase inhibitor in the Notch signal pathway
D - Atoh1 over-expression + g-secretase inhibitor

This is a bit off topic but it would be great to get similar imaging as above done on your own hearing hair cells.

Does anyone know if that is possible? Then you could get confirmation that the problem is missing hair cells and maybe even find out which exact frequencies are gone instead of every 1000 Hz or so in a standard audiogram. Everything is imaged these days e.g. cancer tumors, calcium in heart, etc and hearing loss seems to be lagging behind here as well.