Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[90's Kid]

Dead hair cells are replaced by supporting cells. The details of what happens during regeneration may differ by approach, but the leading idea at the moment is to induce supporting cells to convert into hair cells.

Mmh I get it now.

I heard about "outer hair cells" and "inner hair cells"
Is tinnitus bound with one of them (maybe both ?) and will supporting hair cells replace one of them (outer or inner) ?

 

[DoNotGoGentle]

Can't remember what article it was but once they change the supporting ear hair cells that will change the function of hearing and not be as clear. Maybe only half the band not full band in regards to hearing.

 

[Aaron123]

Is tinnitus bound with one of them (maybe both ?)

Unclear, but likely both.

will supporting hair cells replace one of them (outer or inner) ?

This will remain to be seen, but recent work has shown that both inner and outer HCs can be targeted.

Can't remember what article it was but once they change the supporting ear hair cells that will change the function of hearing and not be as clear.

There is the concern that approaches that directly transform supporting cells into hair cells may affect subsequent hearing. The issue is that supporting cells are lost in this approach. This issue should not be a problem for approaches that cause supporting cells to divide before converting some of them to HCs. In that case you will have both supporting cells and new hair cells. This is an important issue to pay attention to when reading papers.

 

[DoNotGoGentle]

Mmh I get it now.

I heard about "outer hair cells" and "inner hair cells"
Is tinnitus bound with one of them (maybe both ?) and will supporting hair cells replace one of them (outer or inner) ?

I have high frequency loss and noise notch. My high pitch tinntus did not start until I lost hearing at 16 hz I believe so. Both forsure

 

[tomytl]

Unclear, but likely both.


This will remain to be seen, but recent work has shown that both inner and outer HCs can be targeted.


There is the concern that approaches that directly transform supporting cells into hair cells may affect subsequent hearing. The issue is that supporting cells are lost in this approach. This issue should not be a problem for approaches that cause supporting cells to divide before converting some of them to HCs. In that case you will have both supporting cells and new hair cells. This is an important issue to pay attention to when reading papers.

And what happens with the Frequency approach? I guess, if they really can retrigger the natural cycle of growing hair cells it's the only possibility. How would hair cells be able to grow on the right place with the correct lenght?
It's such a complicated task, for a layperson like me a big mysteriun.

 

[papu]

There is the concern that approaches that directly transform supporting cells into hair cells may affect subsequent hearing. The issue is that supporting cells are lost in this approach. This issue should not be a problem for approaches that cause supporting cells to divide before converting some of them to HCs. In that case you will have both supporting cells and new hair cells. This is an important issue to pay attention to when reading papers.

That is correct, some researchers are worried about the role that supporting cells migth play in the hearing of mammals and therefore what kind of hearing you will get after you lost the supporting cells in the procedure. As i understand it frequency approach uses the supporting cells without dividing them first so you will probably loose them in the procedure.

 

[papu]

And what happens with the Frequency approach? I guess, if they really can retrigger the natural cycle of growing hair cells it's the only possibility.

Evolution is a bitch there is a reason for why the regeneration of hair cells is stop in mammals and it might have something with the fidelity of human hearing. Who knows i guess thats why frequency has not injected any one yet.

 

[DoNotGoGentle]

Evolution is a bitch there is a reason for why the regeneration of hair cells is stop in mammals and it might have something with the fidelity of human hearing. Who knows i guess thats why frequency has not injected any one yet.

Really they use supporting cells? Progenitor cells are supporiting? I understand once those are gone then they won't regenerate. I thought they wanted to trigger a second regen like when we are made in the womb.

 

[Aaron123]

And what happens with the Frequency approach?

As I understand it, Frequency is interested in the approach where supporting cells divide and then differentiate thus maintaining the population of supporting cells. (If you look at the paper from February, they talk about expansion and differentiation. Now, we don't need the 2000 fold expansion that they talk about.

How would hair cells be able to grow on the right place with the correct lenght?

This is a great question and is unknown from the published literature. I think the idea is that if they can start the process, some of the signalling will take place naturally. I guess the idea would be that the location of the supporting cells provides some clue as the specific properties of the appropriate hair cell for that location. I don't know of a paper that addresses this specifically, but I am hoping the next paper from that group might shed some light on this.

Progenitor cells are supporiting?

Yes.

I understand once those are gone then they won't regenerate.

See above. As I understand it, if Frequency's approach works, they won't be gone.

 

[tomytl]

As I understand it, Frequency is interested in the approach where supporting cells divide and then differentiate thus maintaining the population of supporting cells. (If you look at the paper from February, they talk about expansion and differentiation. Now, we don't need the 2000 fold expansion that they talk about.


This is a great question and is unknown from the published literature. I think the idea is that if they can start the process, some of the signalling will take place naturally. I guess the idea would be that the location of the supporting cells provides some clue as the specific properties of the appropriate hair cell for that location. I don't know of a paper that addresses this specifically, but I am hoping the next paper from that group might shed some light on this.


Yes.

See above. As I understand it, if Frequency's approach works, they won't be gone.

Thank you for clarify,

another concern I have: in some microscopic pictures from hair cells, you can see that some of them has visible connections on the top. So I just can imagine, that if there is really "just" a break keeping the organ from it's regenerative process, like gowing hair or fingernails. ...
It's hard to imagine how a cell can find all connections again...
Maybe I need to ask this a top notch researcher in this field I know for years.

 

[Aaron123]

another concern I have: in some microscopic pictures from hair cells, you can see that some of them has visible connections on the top.

Yes, "tip links".

So I just can imagine, that if there is really "just" a break keeping the organ from it's regenerative process, like gowing hair or fingernails. ...
It's hard to imagine how a cell can find all connections again...

I am not quite sure I understand, but I think we simply don't know a lot about any of these regenerative processes at this point. I know people study tip links, but I don't believe any of the approaches being talked about here would regrow missing links. I would assume that regenerated hair cells would have tip links, but it seems unlikely that links would form with existing hair cells. No idea the effect this would have on hearing.

 

[tomytl]

Yes, "tip links".

I am not quite sure I understand, but I think we simply don't know a lot about any of these regenerative processes at this point. I know people study tip links, but I don't believe any of the approaches being talked about here would regrow missing links. I would assume that regenerated hair cells would have tip links, but it seems unlikely that links would form with existing hair cells. No idea the effect this would have on hearing.

Once, a researcher told me, that the newly regenerated hair cell would at least find it's way to the nerve connection..so rebuilding also the nerve system and connect correctly.
With tip links, I need to ask...I even don't know what they are good for


https://en.wikipedia.org/wiki/Tip_link

 

[dmorg]

I would like to reaffirm Aaron123's reply (he is usually spot on) as to Frequency's approach of ample progenitor cell division before differentiation. So, I believe,they are not going to "use up" all of the supporting cells. I tend to oversimplify things (sometimes to a fault) but in reading papers and articles regarding Frequency's approach their intention is to initiate the regeneration process and (we've seen this phrase before) allow the "natural cascade of events" handle the rest. Their claim is that the regenerated cells they have produced (in various mammals) appear to have all the necessary parts and pieces required of functioning hair cells. Unfortunately, we can't yet ask a mouse or monkey to pass a speech discrimination test at this point. I am anxiously awaiting the start of their human trials like the rest of you. I tend to believe Frequency's approach will have at least some measurable positive result. Looking at photos of regenerated hair cell bundles, while impressive, do not appear to be quite as neatly "organized" as the original healthy bundles which concerns me. Will this matter ? Probably yes on some level.

 

[tomytl]

I would like to reaffirm Aaron123's reply (he is usually spot on) as to Frequency's approach of ample progenitor cell division before differentiation. So, I believe,they are not going to "use up" all of the supporting cells. I tend to oversimplify things (sometimes to a fault) but in reading papers and articles regarding Frequency's approach their intention is to initiate the regeneration process and (we've seen this phrase before) allow the "natural cascade of events" handle the rest. Their claim is that the regenerated cells they have produced (in various mammals) appear to have all the necessary parts and pieces required of functioning hair cells. Unfortunately, we can't yet ask a mouse or monkey to pass a speech discrimination test at this point. I am anxiously awaiting the start of their human trials like the rest of you. I tend to believe Frequency's approach will have at least some measurable positive result. Looking at photos of regenerated hair cell bundles, while impressive, do not appear to be quite as neatly "organized" as the original healthy bundles which concerns me. Will this matter ? Probably yes on some level.

Your concerns are similar to mine. I read about HCR since 2003 and the headlines of the discoveries sounds almost the same.
Ofcourse, the research has made very big advances and you can nearly find everyday some news in this field.
But yes, if I see pictures or regenersted hair cells it's still a kind of disorderbin the picture. Or another thing, did someone really claim that their approaches work the same as in adult inner ear?
Mostly they are talking about embryo ears or new born ears.
In the other hand, if you read Frequency's approach, it sound very certain and a kind of easy....if you read the news of Hough Ear Institute it also sounds like they are already able to do with their "we have the key" campain. But in HEI's case I think they like to attract more donators.
If you look at Sound Pharmaceuticals regenerative pipeline, the bar of progress didn't move sine 2003. In 2005 they released some of their future plans in the wall street journal. I remember that they wrote, when they are finished with the inner ear regenerative program in 2012 they will move to the eyes...
It sounded also very certain I still have this paper, but I don't want to blame them, because I'm sure they would have if they could. At least they gave me hope in my darkest hours.

 

[jeff W]

How would hair cells be able to grow on the right place with the correct lenght?

What I find quite spooky is not just that avians can regenerate hair cells, but that they can do so in such a precise manner, what I have read is that their ears know how to selectively replace "only" the damaged hair cells and can restore hearing up to 99 percent of pre-injury range, this indicates a complex signalling system which occurs post lesion. From what I understand they are still unravelling how this is done, although Aaron may have more up to date knowledge.

 

[tomytl]

What I find quite spooky is not just that avians can regenerate hair cells, but that they can do so in such a precise manner, what I have read is that their ears know how to selectively replace "only" the damaged hair cells and can restore hearing up to 99 percent of pre-injury range, this indicates a complex signalling system which occurs post lesion. From what I understand they are still unravelling how this is done, although Aaron may have more up to date knowledge.

I think there must be a given programm, otherwise I can't imagine how things should grow correctly on the right place when a gel diffunds in the inner ear.
It's so exciting, but unfortunately speculative and many years away.
Wouldn't it be a candidate for a fast track FDA trial?

 

[BraveNewWorld]

What I find quite spooky is not just that avians can regenerate hair cells, but that they can do so in such a precise manner, what I have read is that their ears know how to selectively replace "only" the damaged hair cells and can restore hearing up to 99 percent of pre-injury range, this indicates a complex signalling system which occurs post lesion. From what I understand they are still unravelling how this is done, although Aaron may have more up to date knowledge.

Bats can regenerate their hearing too. I can't wait until we can unlock the process behind animals with hair cell regeneration and apply it to humans. Nobel Prize worthy.

 

[Iliasp]

If they did not figure this out already how can they claim that there will be clinical trials within 18 months? I dont get it (referring to frequency tx)

 

[NatureHiker]

@Iliasp

From what I've heard, its because they have promising animal data and a lot of the drugs they are using are already FDA approved.

 

[jeff W]

I think there must be a given programm, otherwise I can't imagine how things should grow correctly on the right place when a gel diffunds in the inner ear.
It's so exciting, but unfortunately speculative and many years away.
Wouldn't it be a candidate for a fast track FDA trial?

I don't know about FDA procedure, but I can tell you this, the peer review process is sped up for groundbreaking papers, more folk are recruited to hasten the process, so theoretically the standard of proof although objective in theory, should be higher for work in this area, I think that is a good thing.

 

[Reinier]

Here is something I am thinking about lately.

I wonder that when in future it is possible to regenerate hair-cells in the inner ear, what will happen with our perception of sounds.
After all, new connections are made to new hair-cells.

I have read a story where someone needed to relearn smells again after regeneration and rewiring of olfactory bulb.
I understand that smells where completely different and not recognisable again. https://academic.oup.com/chemse/art.../Regeneration-and-Rewiring-the-Olfactory-Bulb

Could it be that sounds will be completely different and worse, not recognisable?

Is it possible to have partial regenerated hearing and not a complete "reboot".
My right ear is much worse than my left ear. What will happen if my worse ear will get treatment. Will sounds be different in my right ear? That will be a challenge for my brain (-;

I understand it is all speculation. There is no example of regenerated hair-cells and connections.

 

[tomytl]

f

Here is something I am thinking about lately.

I wonder that when in future it is possible to regenerate hair-cells in the inner ear, what will happen with our perception of sounds.
After all, new connections are made to new hair-cells.

I have read a story where someone needed to relearn smells again after regeneration and rewiring of olfactory bulb.
I understand that smells where completely different and not recognisable again. https://academic.oup.com/chemse/art.../Regeneration-and-Rewiring-the-Olfactory-Bulb

Could it be that sounds will be completely different and worse, not recognisable?

Is it possible to have partial regenerated hearing and not a complete "reboot".
My right ear is much worse than my left ear. What will happen if my worse ear will get treatment. Will sounds be different in my right ear? That will be a challenge for my brain (-;

I understand it is all speculation. There is no example of regenerated hair-cells and connections.

Hi,
my guess and speculation:
If we could get some hearing back, it depends how it would happen. Since hair cells would take some time to grow and develop, it might be like a fade in effect.
I can imagine it's like you get a hearing aid and then you probably think all is to lud first until the brain regulates it, since you maybe remember the sound.
In my case, always when I flash the toilett, I realize how wrong it sounds, so I think I haven't fogotten the real sound of flashing water ....probably because this was my first action after sudden hearing loss when I stand up and realized my newly accuired hearing loss in 2003.

 

[Reinier]

I realize how wrong it sounds, so I think I haven't fogotten the real sound of flashing water

I wonder how accurate our auditive memory is. It is after all subjective.

Since hair cells would take some time to grow and develop, it might be like a fade in effect.

This effect would be so awesome. Just imagine! I think that is something that will make me emotional when this should happen.

Also when hair-cells can be regenerated, it should happen in the damaged section of the inner ear.
The nerves that connect to these hair-cells reside in this area. So the hair cells in the 4 kHz section of the cochlea will most likely not connect to the 8 kHz section of our brain.
I seem to remember that someone participating in the GenVec trial was able to hear "new" frequencies, but speech understanding was not improved. I think that is important. If frequencies we already hear just get louder (lets say from 60 dB loss to 20 dB loss) we will have no difficulty. But if we hear new frequencies it could be different.

In my case, always when I flash the toilett, I realize how wrong it sounds

It also depends if both ears are damaged. In my case my left ear is my "reference" ear.

But is is just a thought.
I hope we will find out relatively soon.

 

[tomytl]

I wonder how accurate our auditive memory is. It is after all subjective.


This effect would be so awesome. Just imagine! I think that is something that will make me emotional when this should happen.

Also when hair-cells can be regenerated, it should happen in the damaged section of the inner ear.
The nerves that connect to these hair-cells reside in this area. So the hair cells in the 4 kHz section of the cochlea will most likely not connect to the 8 kHz section of our brain.
I seem to remember that someone participating in the GenVec trial was able to hear "new" frequencies, but speech understanding was not improved. I think that is important. If frequencies we already hear just get louder (lets say from 60 dB loss to 20 dB loss) we will have no difficulty. But if we hear new frequencies it could be different.

It also depends if both ears are damaged. In my case my left ear is my "reference" ear.

But is is just a thought.
I hope we will find out relatively soon.

the Genvec trial is likely a treatment in a very high experimental manner. I'm happy that there is progress,
but in the hair cell researcher scene it's highly doubted that this can work like they know things
from the papers. But at least, it was a gene therapy and until now, we didn't read about any terrible
side effects.
I guess, and I just probably hope too much, the molecular therapies coming next will do a much better job...
but without a test, no party at all

 

[NatureHiker]

Here is something I am thinking about lately.

I wonder that when in future it is possible to regenerate hair-cells in the inner ear, what will happen with our perception of sounds.
After all, new connections are made to new hair-cells.

I have read a story where someone needed to relearn smells again after regeneration and rewiring of olfactory bulb.
I understand that smells where completely different and not recognisable again. https://academic.oup.com/chemse/art.../Regeneration-and-Rewiring-the-Olfactory-Bulb

Could it be that sounds will be completely different and worse, not recognisable?

Is it possible to have partial regenerated hearing and not a complete "reboot".
My right ear is much worse than my left ear. What will happen if my worse ear will get treatment. Will sounds be different in my right ear? That will be a challenge for my brain (-;

I understand it is all speculation. There is no example of regenerated hair-cells and connections.

I understand that we have cured blindness in some people that have been blind since birth. They had to undergo therapy and brain training for weeks to months before they could comprehend visual cues. With hearing regeneration i'd assume you'd need some therapy/training to have your brain recomprehend the new frequencies.

Unless your auditory nerve and/or brain is damaged then you already have the components necessary to rewire your hearing given your cochlear hair cells are restored and properly transmitting.

Your concern is valid, but i don't think it's a big hurdle

 

[swc5150]

I would think the brain re-booting timeframe would depend on how severe the hearing loss? Like the blind person scenario, if you go from completely blind to sight, I have no doubt your brain would have to adapt. Being slightly farsighted, I can put on some reading glasses and my brain sees up close immediately. Also, my buddy with HA's (about 60% hearing loss I think?) regains hearing immediately after putting them in. Hopefully we get the answer soon.

 

[Reinier]

Thinking about it and reading the posts I think we can think of two scenario:
One: hearing new frequencies.
Two: is improving of frequencies that are down but not completely lost.
Hearing new frequencies will be a challenge for the brain. When one ear is damaged and regenerated you will not hear new frequencies. You recognise the frequencies from the "healthy" ear.
But if the "rewiring" of new hair-cells goes awry it could get interesting.
I will try to stop my thoughts about this. I need Zen therapy

 

[RB2014]

Thinking about it and reading the posts I think we can think of two scenario:
One: hearing new frequencies.
Two: is improving of frequencies that are down but not completely lost.
Hearing new frequencies will be a challenge for the brain. When one ear is damaged and regenerated you will not hear new frequencies. You recognise the frequencies from the "healthy" ear.
But if the "rewiring" of new hair-cells goes awry it could get interesting.
I will try to stop my thoughts about this. I need Zen therapy

When we were born, we heard new frequencies and slowly over time adapted to them and learned what they meant. Now we will have to do it all over again, but its the second time and should be easier. If you wear hearing aides then those frequencies were never lost just amplified. I have high hopes for this. I wouldn't overthink it. The worst case would be that it takes time to relearn all of the words you already knew but have been distorted over the years due to the lost frequencies.

The girl that reported new frequencies in the genvec trial might have needed time to adapt and relearn all of the words she already new but had become distorted over time.

 

[Reinier]

Now we will have to do it all over again, but its the second time and should be easier.

Yes, I agree. We have a "database" we can use . We also use this more extensively when our hearing is not tip/top any-more.

I wouldn't overthink it.

I think that is what I am doing.

 

[jeff W]

I understand that we have cured blindness in some people that have been blind since birth. They had to undergo therapy and brain training for weeks to months before they could comprehend visual cues. With hearing regeneration i'd assume you'd need some therapy/training to have your brain recomprehend the new frequencies.

Unless your auditory nerve and/or brain is damaged then you already have the components necessary to rewire your hearing given your cochlear hair cells are restored and properly transmitting.

Your concern is valid, but i don't think it's a big hurdle

Great point, its common sense to look at how other organs behave and hazard a guess that this cranial nerve pathway will function likes others. Look at olfaction, the nose possesses a powerful regeneration system unlike anything else in the body, its nerves being constantly exposed to toxic agents and pathogens are routinely damaged, only to return using ensheathing cells to guide nerve tissue, but when the olfaction system is damaged temporarily do you forget smell? Of course not. It simply returns and your body perceives smell as the pathways that form the perception are functional again. The ear has a natural functional purpose, it will (in my opinion) turn out to be a very intelligent organ, being able to do things far beyond what neuroscience currently believes.