Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Enclave]

https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(19)30111-X.pdf

Review of current pharmacological approaches to treating hair cell regeneration. Audion, FX-322, and CGF166 are all reviewed with perspectives of where research stands today, and where it needs to go in the future to enhance these approaches.

 

[tarmaced]

https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(19)30111-X.pdf

Review of current pharmacological approaches to treating hair cell regeneration. Audion, FX-322, and CGF166 are all reviewed with perspectives of where research stands today, and where it needs to go in the future to enhance these approaches.

So, I read this and was not optimistic . It seemed to advocate a multi-strategy approach, and implied that the current strategies would not work in isolation. Do any of the big names in hearing regeneration utilise such a multi-payload system?

 

[tarmaced]

Sorry - I have read it in full now. So yes FX-322 is 'combinational'. If this is the only such example then my hopes are still impacted - a one horse race is less reassuring.

 

[JohnAdams]

Sorry - I have read it in full now. So yes FX-322 is 'combinational'. If this is the only such example then my hopes are still impacted - a one horse race is less reassuring.

They've shown hearing improvement in animal models and are going to present trial data in 10 weeks showing improvement in humans. It works. Have hope.

 

[d'Wooluf]

Sorry - I have read it in full now. So yes FX-322 is 'combinational'.

It's maybe worse than that. I think what they are saying is that in addition to what Frequency Therapeutics is doing you might need to look at gene manipulation (e.g., CRISPR/CAS9). There's some commentary on it at https://hearinghealthfoundation.org/blogs (2nd article down at the moment).

 

[tarmaced]

They've shown hearing improvement in animal models and are going to present trial data in 10 weeks showing improvement in humans. It works. Have hope.

It would be nice to see some long term improvement monitoring in the next study (or this one!)

 

[Enclave]

"There has been some success in hair cell regeneration following Wnt and Notch modulation in the mature mammalian cochlea.34,52 However, it is important to note that many of these newly generated hair cells show limited survival and do not appear to fully differentiate, lacking mature stereocilia, and they may fail to form proper synaptic connections with auditory neurons.75"

In my opinion the conclusion falls short in a big way. Citation 75 is a study from 2014... several years prior to the McLean 2017 paper and doesn't utilize the same molecular approach, so essentially they're utilizing an outdated publication to debunk FX-322. Also interesting, this paper only cites FTX's Phase 1a study, and no mention of their Phase 1b study where they specifically state they saw hearing improvement in their test subjects.

 

[Enclave]

The presentation Frequency is doing in September is only going to be 5min long.

That's a less than inspirational time slot.

 

[Daniel Lion]

"There has been some success in hair cell regeneration following Wnt and Notch modulation in the mature mammalian cochlea.34,52 However, it is important to note that many of these newly generated hair cells show limited survival and do not appear to fully differentiate, lacking mature stereocilia, and they may fail to form proper synaptic connections with auditory neurons.75"

In my opinion the conclusion falls short in a big way. Citation 75 is a study from 2014... several years prior to the McLean 2017 paper and doesn't utilize the same molecular approach, so essentially they're utilizing an outdated publication to debunk FX-322. Also interesting, this paper only cites FTX's Phase 1a study, and no mention of their Phase 1b study where they specifically state they saw hearing improvement in their test subjects.

You're clever...

I read the same text and didn't catch what you did. Mind you I usually need to read these a few times as I have no scientific background. A degree in fine arts, sculpture, doesn't really set me up for notch modulation... I have learned a lot and appreciate your post.

Anything that gives me a glimmer of optimism is nice.... thanks for the post.

And yes five minutes? The waiting game....gotta stay distracted with this illness

 

[tarmaced]

The presentation Frequency is doing in September is only going to be 5min long.

That's a less than inspirational time slot.

Part of me agrees... but what do we expect them to say and how long do we think it will take them to say it? Assumign that everyone present is familiar with their work...
8 people had the drug.
No side effects observed (fingers crossed).
An average of X db improvement was observed at XKhz.
An average of X db improvement was observed at XKhz.
We will be running phase 2b, that will last X on 20XY for months.
I hope

 

[d'Wooluf]

The presentation Frequency is doing in September is only going to be 5min long.

That's a less than inspirational time slot.

True. But aren't like five of them going to be there?

 

[Pero1234]

Person 1: We
Person 2: cured
Person 3: hearing loss!
Person 4: Any
Person 5: questions?

4 mins remaining...

;-)

 

[JohnAdams]

Part of me agrees... but what do we expect them to say and how long do we think it will take them to say it? Assumign that everyone present is familiar with their work...
8 people had the drug.
No side effects observed (fingers crossed).
An average of X db improvement was observed at XKhz.
An average of X db improvement was observed at XKhz.
We will be running phase 2b, that will last X on 20XY for months.
I hope

16 had the drug, 8 had placebo. Right?

 

[tarmaced]

16 had the drug, 8 had placebo. Right?

As I remember it was 8 8. Haven't checked today am probably wrong...

 

[grate_biff]

As I remember it was 8 8. Haven't checked today am probably wrong...

No, there was 24, 8 low dose, 8 high dose and 8 placebo.
They ended up with 23, I do not know which group he/she was in.

 

[Chinmoku]

https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(19)30111-X.pdf

Review of current pharmacological approaches to treating hair cell regeneration. Audion, FX-322, and CGF166 are all reviewed with perspectives of where research stands today, and where it needs to go in the future to enhance these approaches.

No mentioning of REGAIN?

 

[Don Tinny]

So it's something very very difficult to repair. And you can ruin your ears with some loud Heavy Metal songs, it's that easy. Just thinking about it...

 

[Enclave]

No mentioning of REGAIN?

Audion is REGAIN

 

[PolishSoldier87]

Are there any supplements/regimines or research on the horizon for channelopathies that also affect the potassium ion channels in the brainstem? Anyone know if brainstem toxicity can still heal/improve after 6 months? I'm just hoping it still can.

Yes. Brain toxicity can improve for many months/years. You don't know if you have dead hair cells. The best way to know that is to do high frequency OAE test up to 20 kHz. It tests if your hair cells physically exist. The same damage to high frequency was made to one member of Tinnitus Talk who have Lyme's disease and took a herb that hit the Lyme and probably toxins damaged something. That herb was otoprotective itself so there wasn't a chance for some kind ototoxicity. I had also Lyme. I took amoxicillin and further doxycycline. Both of them damaged my hearing some way but it's more probable that it hit Lyme and I had neurolyme so my brain was a battlefield and many toxins was produced that damaged something in the brainstem. Brainstem has to have balanced conditions and if there are some complications, one or more things are out of tune, it can affect others. For example tinnitus --> visual snow.

For now I recommend for you to take an extract from Turmeric and Curcumin (with Piperine, which increases bioavilability of curcumin by some thousand percent - confirmed by researchers).

"A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. .(...)
The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties."
https://www.biomedcentral.com/about/press-centre/science-press-releases/26-sep-2014

I know that this wont regaim your HC becouse its impossible for now (by the way curcumin blocks extraction of Atoh1 moreover) but it can silent your brainstem and make it work more normally. I had not get back my 12+khz in my one ear (thats the damage) but my hearing is much much improved all range except that and tinnitus cured by 95 percent. Sometimes 99 percent.

 

[PolishSoldier87]

Although curcumin is otoprotective, do not take curcumin after acute trauma because it blocks extraction of Atoh1 and can stop spontaneous regeneration of hearing. Extraction of Atoh1 is a main condition during self healing of the hearing that happen during the first weeks after trauma. It's very weak and of course only to some level but it exists.

 

[FGG]

Yes. Brain toxicity can improve for many months/years. You don't know if you have dead hair cells. The best way to know that is to do high frequency OAE test up to 20 kHz. It tests if your hair cells physically exist. The same damage to high frequency was made to one member of Tinnitus Talk who have Lyme's disease and took a herb that hit the Lyme and probably toxins damaged something. That herb was otoprotective itself so there wasn't a chance for some kind ototoxicity. I had also Lyme. I took amoxicillin and further doxycycline. Both of them damaged my hearing some way but it's more probable that it hit Lyme and I had neurolyme so my brain was a battlefield and many toxins was produced that damaged something in the brainstem. Brainstem has to have balanced conditions and if there are some complications, one or more things are out of tune, it can affect others. For example tinnitus --> visual snow.

For now I recommend for you to take an extract from Turmeric and Curcumin (with Piperine, which increases bioavilability of curcumin by some thousand percent - confirmed by researchers).

"A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. .(...)
The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties."
https://www.biomedcentral.com/about/press-centre/science-press-releases/26-sep-2014

I know that this wont regaim your HC becouse its impossible for now (by the way curcumin blocks extraction of Atoh1 moreover) but it can silent your brainstem and make it work more normally. I had not get back my 12+khz in my one ear (thats the damage) but my hearing is much much improved all range except that and tinnitus cured by 95 percent. Sometimes 99 percent.

I believe I have both brainstem and cochlear damage. I have moderately severe hearing loss in both ears at 12000hz but I also have really bizarre distortions at all frequencies (I can listen to a song and whole parts/instruments/notes/cords are missing unless I isolate them, difficulty in localizing sounds and inability to listen to music.

I found studied showing aminoglycosides can damage/deform the kv3.1 ion channels in the brain stem *and* hair cells in cochlea. I believe Macrolides have affected me the same way. I'm now hoping for Autifony's kv3.1 drug, so I can maybe try it off label and Frequency's drug for hair cells.

Thanks so much for writing all of that out. I do take tumeric but not a huge amount as I'm an abnormal MAO-B gene homozygote and MAO-A heterozygote and it can have a lot if effects. I'd maybe chance it if i could hear music again, though.

I know neurons can sometimes heal with time but I'm not sure about synaptic ion channel deformations. Anyone know more?

 

[ChrisBoyMonkey]

I believe I have both brainstem and cochlear damage. I have moderately severe hearing loss in both ears at 12000hz but I also have really bizarre distortions at all frequencies (I can listen to a song and whole parts/instruments/notes/cords are missing unless I isolate them, difficulty in localizing sounds and inability to listen to music.

I found studied showing aminoglycosides can damage/deform the kv3.1 ion channels in the brain stem *and* hair cells in cochlea. I believe Macrolides have affected me the same way. I'm now hoping for Autifony's kv3.1 drug, so I can maybe try it off label and Frequency's drug for hair cells.

Thanks so much for writing all of that out. I do take tumeric but not a huge amount as I'm an abnormal MAO-B gene homozygote and MAO-A heterozygote and it can have a lot if effects. I'd maybe chance it if i could hear music again, though.

I know neurons can sometimes heal with time but I'm not sure about synaptic ion channel deformations. Anyone know more?

Not sure about natural healing but Dr. Tzounopoulos of the University of Pittsburgh is also working on a potassium ion modulator they are calling RL-81 funded by the DoD. It's a remake of trobalt, being redesigned peimarily for the treatment of tinnitus.

 

[Tinniger]

Inner Ear Hair Cell Damage — Maybe We Can Know More

I would be glad to know, whether my tinnitus is due to inner ear cell damage, - or not.
If not, I don't need any hair cell regeneration....

In my opinion, therapies for tinnitus are always being considered without having made an exact diagnosis. Tinnitus is not a diagnosis, but a symptom.

 

[JohnK]

Is it possible macrolide ototoxicity affected the auditory center in my brain stem as well? How would anyone know if they have brainstem involvement with their hearing loss and tinnitus? I'm really hoping this is is not the case for me because that means no treatment on the horizon would help me .

I find it very improbable that something would cause neurological damage but only in one specific region of the brain that's really far from the ears.

 

[FGG]

I find it very improbable that something would cause neurological damage but only in one specific region of the brain that's really far from the ears.

https://www.ncbi.nlm.nih.gov/pubmed/15547932/

Why not? It happens with aminoglycoside antibiotics sometimes (see link above). This happens when drugs only bind to and deform one type of potassium ion channel (in this case, KV3.1 channels--which have a lot to do with the dynamic quality of sound and aren't found in mass elsewhere).

 

[JohnK]

The initial work to discover this was done in the Heller Lab at Stanford University. One of the people over this lab is Robert Jackler. In a presentation he stated that once the hair cell is regenerated that the nerve regrows and reconnects. He called it a "god darned miracle".

start at around 28:00

Great video! Interestingly he said "in 10 years" and this was 2012. Would we still be on track for the early 2020s?

 

[ChrisBoyMonkey]

Great video! Interestingly he said "in 10 years" and this was 2012. Would we still be on track for the early 2020s?

Frequency Therapeutics might make that happen.

 

[Daniel Lion]

Frequency Therapeutics might make that happen.

Not might... will make this happen.

 

[bell]

Great video! Interestingly he said "in 10 years" and this was 2012. Would we still be on track for the early 2020s?

In 2005 they said "in 10 years" too...

 

[tarmaced]

In 2005 they said "in 10 years" too...

I appreciate you are a pessimist due to your experiences. This is very valid position to take. But what has really struck me is that most of the studies relevant to this stuff that I am referencing in the last two pages have been produced within the last decade. Identifying the cell types, finding them in human ears, identifying how to make them replicate... I would imagine, due to this, that our understanding has increased a fair bit - we are way in front of our 2005 selves.