Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[tomytl]

Hair Cell Regeneration right now is entirely speculative about its outcomes in humans. The notion that regenerating hair cells leads to an improved hearing is entirely speculative too. Researchers believe this to be the case because when birds are deafened and their hair cells are grown back they are able to recognize the same calls as they were before. Hence, the reasoning is this same principle applies to humans. However, this could easily not be the case. There could be some auditory process in the brain that is altered when hearing is lossed.

I don't think there is any reason to believe that a re-grown hair will be diminished in quality if it's exactly like a pristine one. However, this is speculative.

@tomytl He's saying, that imagine you have a 70 decibel loss flat across all the measured frequencies or just some. Then the best you could do is go back to 20 to 25 decibel loss. That is a huge improvement though. But no one knows how much hearing targeted specific regenerative medicine for the ear will restore or what frequencies it might be most effective at.

I'm also not aware of any stem cell or laser therapy that has been able to demonstrate a significant improvement in hearing though.

Thanks NeoM for you expertise.
I thought, they could also functional regenerate hearing in mammals... but I guess, it's a kind of
difficult to ask them about the quality.
So we have to wait until it's in the human trials. It's anyway a kind of difficult to imagine such a
procedere... But there are so many biotech companies, so one might be successful one day.


Greets tomytl

 

[tomytl]

Interesting, how hearing aid traders see the future.
http://www.amplifon.co.uk/hearing-aids/hearing-aids-explained/history-and-future-of-hearing-aids/

 

[JohnG]

I would like to see where in the research it says that new, regenerated hair cells would only hit 25db. I don't think that is an accurate statement. I also don't think it is accurate to state that regenerating some cells among some damaged cells would not enhance better hearing. Any statement seems very speculative at best.

The human trails from GenVec after phase I will be very telling since it is a therapeutic dose.

 

[JohnG]

Ok, I wrote an email to GenVec...I was trying to dig for how long they think the trials will last and who might be enrolled. I got this response:

"– Thanks for your interest. I am sorry to hear about the Tinnitus. I don't think we can answer your questions re timing. The drug is being developed by our partner, Novartis, and there is simply no way that we (or at this early stage, Novartis) could provide a truly accurate reading on how long before all Phase II exploration was completed. I am sorry to disappoint, but we also cannot provide any color on patient eligibility and exclusion criteria for a Phase III. It might interest you to review the presentation that Novartis made concerning the CGF166, as well as the structure of the upcoming clinical trial, to the Recombinant DNA Advisory Committee of the NIH (the RAC). This was publicly presented in December 2013. Here is the link, fyi: http://videocast.nih.gov/launch.asp?18200

CGF166 was the first trial to be considered by the RAC that morning, so after a few minutes of routine meeting business and discussions, you will see the CGF166 begin – I believe it is approximately at minute 6 of the weblink. Wishing you all the best – "

I sent them a kind response:

"There are many of us following your company on tinnitustalk.com who suffer sudden hearing loss and Tinnitus. This is a tremendous breakthrough ..."

Well, I tried to get more info but at least we know they respond!

 

[attheedgeofscience]

I would like to see where in the research it says that new, regenerated hair cells would only hit 25db. I don't think that is an accurate statement. I also don't think it is accurate to state that regenerating some cells among some damaged cells would not enhance better hearing. Any statement seems very speculative at best.

The human trails from GenVec after phase I will be very telling since it is a therapeutic dose.

First of all, I know because I have studied a great deal of research before my two stem cell treatments. But more importantly, the information I am referring to, is even in GENVEC's own company material...!

However, the overall point I am making is that - even if I was wrong (which I am not) - restoration of hearing is not necessarily a guarentee of reduction/elimination of tinnitus. For that you would need a targeted treatment such as what the folks at Auris Medical are developing.

Applied science and hearing restoration is interesting, but you guys are chasing a false lead when it comes to tinnitus.

 

[tomytl]

First of all, I know because I have studied a great deal of research before my two stem cell treatments. But more importantly, the information I am referring to, is even in GENVEC's own company material...!

However, the overall point I am making is that - even if I was wrong (which I am not) - restoration of hearing is not necessarily a guarentee of reduction/elimination of tinnitus. For that you would need a targeted treatment such as what the folks at Auris Medical are developing.

Applied science and hearing restoration is interesting, but you guys are chasing a false lead when it comes to tinnitus.

View attachment 938

Hi,
for people with hearing loss probably might be helpful, if the hair cells really work.
At least, we just can speculate. For people with hearing loss and Tinnitus, hair cell regeneration
might be interesting.

Greets Tom

 

[JohnG]

However, the overall point I am making is that - even if I was wrong (which I am not)

Ah, so very scientific...so very scientific. Even the chart you plastered up showed a high level of db improvement so what is your point again..?

I do agree that Tinnitus is about the brain...and indeed if we put back the cilia in the cochlea, there might still be a disconnect. But I don't think this is chasing a dream, as many people have hearing loss they want to recover.

Maybe they will need something like that from Auris, if it works, that will also quiet the brain down so it can receive the signal better from those regrown hair cells.

 

[attheedgeofscience]

However, the overall point I am making is that - even if I was wrong (which I am not)

Ah, so very scientific...so very scientific. Even the chart you plastered up showed a high level of db improvement so what is your point again..?

I do agree that Tinnitus is about the brain...and indeed if we put back the cilia in the cochlea, there might still be a disconnect. But I don't think this is chasing a dream, as many people have hearing loss they want to recover.

Maybe they will need something like that from Auris, if it works, that will also quiet the brain down so it can receive the signal better from those regrown hair cells.

My point is just what I said: an improvement in hearing threshold of 20-25 db (at best) - read the chart...! Debating with a stem cell pioneer will not get you anywhere - I know my stuff...!

 

[nills]

i don`t think the brain is going to keep listening to a tinnitus signal when there is a genuine high freq signal again available ... it`s smart enough to change back. Smarter than we think it is and also smarter than we think we are But untill that moment comes after the first human clinical trials we are just blowing soap bubbles ready to pop at any time ... still pretty though ...

btw Stemceel pioneer, I hope your joking, otherwise relax a bit ... everybody has a right to form an opinion here ... no one has t believe anybody is the king until they show their crown and castle.

 

[attheedgeofscience]

i don`t think the brain is going to keep listening to a tinnitus signal when there is a genuine high freq signal again available ... it`s smart enough to change back. Smarter than we think it is and also smarter than we think we are But untill that moment comes after the first human clinical trials we are just blowing soap bubbles ready to pop at any time ... still pretty though ...

btw Stemceel pioneer, I hope your joking, otherwise relax a bit ... everybody has a right to form an opinion here ... no one has t believe anybody is the king until they show their crown and castle.

It is evident that the JohnG does not seem to know the difference between an improvement in hearing and an improvement in hearing threshold.

 

[nills]

This forum is a place for people to come together and learn from each other. Or learn from the articles that are posted. If something is obvious to you and not to another you can help them by explaining it. just like you had to learn your abc before you could read any of the articles that make up your so called knowledge. We are just evolved monkeys my friend ... the highest form of evolution is not in knowledge but in wisdom and compassion. Your previous post does n`t show any of the latter.

 

[nills]

To get back on topic. That chart shows me alot more than just 25-30 db improvement. IN the damaged and repaired section the orange bar shows up to where the treshold is lowered, isn`t it? So for the 24 khz the damaged hearing could only notice the sound at around 100db and the repaired hearing could notice the sound at around 20db, right?
----------------------------------------
Absolute threshold of hearing
From Wikipedia, the free encyclopedia
The absolute threshold of hearing (ATH) is the minimum sound level of a pure tone that an average ear with normal hearing can hear with no other sound present. The absolute threshold relates to the sound that can just be heard by the organism.[1][2] The absolute threshold is not a discrete point, and is therefore classed as the point at which a response is elicited a specified percentage of the time.[1] This is also known as the auditory threshold.

The threshold of hearing is generally reported as the RMS sound pressure of 20 micropascals. It is approximately the quietest sound a young human with undamaged hearing can detect at 1,000 Hz.[3] The threshold of hearing is frequency dependent and it has been shown that the ear's sensitivity is best at frequencies between 1 kHz and 5 kHz.[3]

 

[attheedgeofscience]

To get back on topic. That chart shows me alot more than just 25-30 db improvement. IN the damaged and repaired section the orange bar shows up to where the treshold is lowered, isn`t it? So for the 24 khz the damaged hearing could only notice the sound at around 100db and the repaired hearing could notice the sound at around 20db, right?
----------------------------------------
Absolute threshold of hearing
From Wikipedia, the free encyclopedia
The absolute threshold of hearing (ATH) is the minimum sound level of a pure tone that an average ear with normal hearing can hear with no other sound present. The absolute threshold relates to the sound that can just be heard by the organism.[1][2] The absolute threshold is not a discrete point, and is therefore classed as the point at which a response is elicited a specified percentage of the time.[1] This is also known as the auditory threshold.

The threshold of hearing is generally reported as the RMS sound pressure of 20 micropascals. It is approximately the quietest sound a young human with undamaged hearing can detect at 1,000 Hz.[3] The threshold of hearing is frequency dependent and it has been shown that the ear's sensitivity is best at frequencies between 1 kHz and 5 kHz.[3]

Agreed.

Improvement in hearing for 24 kHz is about 70 db in the chart shown. Hearing threshold is now about 20 db.

Regrown inner hair cells do not possess the same quality as the ones we are born with. Hence hearing threshold starts at about 20-25 db. Which is what I have been saying all along and which is pretty nicely explained by GENVEC's own chart...

 

[JohnG]

Hey attheedgeofscience, you need to relax man...really.

As the chart shows, I see a huge improvement...huge! I know you are trying to bash the result because you don't see a 25db or better bar.

But that is not what you should interpret this to mean. This means that hair cells definitely grew and it was not just some placebo effect. Indeed, many hairs had to grow to go from say 105 to 45. That is a significant growth.

I also believe that growing more hair cells in the damaged areas would help heal T much faster. The problem is the brain has lost its input to the damaged hair cells and the neurons are firing with the "phantom leg syndrome". Put the signals back and it starts to work again.

This is a huge step and also the work done at Harvard too.

How are you an expert in stem cells?

 

[JohnG]

I see no evidence here to support the statement that these are somehow lower quality hair cells that can barely hit 25db. That is not what this chart shows at all. In fact, the Harvard study would dispute your statement with Notch suppression that stimulates new cells from supporting cells. You simply are not accurate. Sorry.

 

[JohnG]

So if I don't agree with you..this site is a waste of time? That is a mean thing to say. Please go out and have fun. I know it is hard with T. I am suffering too as I write this. It pains me to have this affliction but let's be constructive.

 

[cmurem]

Hey attheedgeofscience, you need to relax man...really.

As the chart shows, I see a huge improvement...huge! I know you are trying to bash the result because you don't see a 25db or better bar.

But that is not what you should interpret this to mean. This means that hair cells definitely grew and it was not just some placebo effect. Indeed, many hairs had to grow to go from say 105 to 45. That is a significant growth.

I also believe that growing more hair cells in the damaged areas would help heal T much faster. The problem is the brain has lost its input to the damaged hair cells and the neurons are firing with the "phantom leg syndrome". Put the signals back and it starts to work again.

This is a huge step and also the work done at Harvard too.

How are you an expert in stem cells?

What seems very intersting to me is how the jobless nerves reattach to the new hair cells and return or remember their former mission..

 

[JohnG]

That is a good point. Seems like the supporting cell near the dead hair cell will connect to the nerve and become the new hair cell. Apparently, the apparatus was there all along but nature turned it of for us unlucky humans but not so for other animals. That is where the Notch inhibition comes in. I posted a link to the Harvard study.

 

[JohnG]

Interesting reads:

http://www.sciencedaily.com/releases/2013/01/130109124201.htm

"In the experiment, the researchers applied a drug to the cochlea of deaf mice. The drug had been selected for its ability to generate hair cells when added to stem cells isolated from the ear. It acted by inhibiting an enzyme called gamma-secretase that activates a number of cellular pathways. The drug applied to the cochlea inhibited a signal generated by a protein called Notch on the surface of cells that surround hair cells. These supporting cells turned into new hair cells upon treatment with the drug. Replacing hair cells improved hearing in the mice, and the improved hearing could be traced to the areas in which supporting cells had become new hair cells."

http://neurowiki2013.wikidot.com/individual:hair-cell-regeneration#toc8

"Notch is a transmembrane receptor known for its role in communication between adjacent cells during embryogenesis. When a cell is differentiating, it will express a Notch ligand which interacts with the Notch receptors of adjacent cells. This interaction triggers a cascade of intracellular events within the adjacent cell which prevent it from entering the same differentiation pathway. This local communication is necessary for the formation of functionally distinct cells which arise from the same progenitor pool [10]. Notch-mediated lateral inhibition is seen in the developing embryo as well as between cells of the cochlea[1]. Notch activation activates γ-secretase, which acts downstream to express the Hes5 gene[17]. Hes5, when present in the cell, prevents the expression of the Atoh1 transcription factor - a factor known to induce hair cell differentiation[3]."

 

[tomytl]

Thanks JohnG for all the updates, very interesting and a kind of hopeful.
Can't wait for the first results of GenVec/Novartis PhaseI trials.

Greest tomytl

 

[NeoM]

@tomytl thanks, but I don't consider myself to have "expertise." I just read what the experts write and try to make sense of it. Personally I think restoration of hair cells will improve hearing.

@JohnG thanks for that video. It really shows what they are trying to do and expect. I didn't realize they also had an ex-vivo experiment showing that some hair cells are grown back in humans. It also shows the concerns about the drug too, i.e. it being so close to the brain and whether it could leak into there and potentially cause tumors. It also seems they are being very modest with what they expect, for good reason, and are looking for a 10 db improvement. It also seems that the drug CGF166 restores high frequencies, i.e. 16 or 32, better than lower frequencies, 8 and below. Hopefully it restores the speech frequencies and there is a big decibel gain too. I guess we will just have to see how the trial goes.

 

[tomytl]

@tomytl thanks, but I don't consider myself to have "expertise." I just read what the experts write and try to make sense of it. Personally I think restoration of hair cells will improve hearing.

@JohnG thanks for that video. It really shows what they are trying to do and expect. I didn't realize they also had an ex-vivo experiment showing that some hair cells are grown back in humans. It also shows the concerns about the drug too, i.e. it being so close to the brain and whether it could leak into there and potentially cause tumors. It also seems they are being very modest with what they expect, for good reason, and are looking for a 10 db improvement. It also seems that the drug CGF166 restores high frequencies, i.e. 16 or 32, better than lower frequencies, 8 and below. Hopefully it restores the speech frequencies and there is a big decibel gain too. I guess we will just have to see how the trial goes.

Hi NeoM,

yeah, it's a kind of expertise You translated from scientific language to my level
Isn't this first 10dB shift depending on the dose of the drug? I think they have to start with low
dosage to see if the inner ear get toxicated, or the brain, or body...
Or can they probably achive better levels with repetition?

 

[JohnG]

yeah...I saw the concerns but apparently atoh1 gene is not tumorigenic from other studies. They claim that the adenovirus has all the deletions so it won't harm the neurons, which apparently would be easy for this adenovirus to splice into due to the proximity to the CNS and the fact that neurons are more susceptible.

The surgery seems pretty tricky (they have to do a stapedectomy after opening the tympanic membrane then inject the dose with that bulky injection machine. They say they are going for full dose to check toxicity. They should pull CNS samples to check viral shedding.

It's amazing how the supporting cells can transdifferentiate into hair cells and reattach to the underlying nerves. I would live to have my high freq hairs to normal..ish db range.

If this works...imagine the doors opening not just for hearing but so many diseases. Using a viral vector that can target defects in our DNA is one exciting approach to what are now incurable diseases!

 

[tomytl]

yeah...I saw the concerns but apparently atoh1 gene is not tumorigenic from other studies. They claim that the adenovirus has all the deletions so it won't harm the neurons, which apparently would be easy for this adenovirus to splice into due to the proximity to the CNS and the fact that neurons are more susceptible.

The surgery seems pretty tricky (they have to do a stapedectomy after opening the tympanic membrane then inject the dose with that bulky injection machine. They say they are going for full dose to check toxicity. They should pull CNS samples to check viral shedding.

It's amazing how the supporting cells can transdifferentiate into hair cells and reattach to the underlying nerves. I would live to have my high freq hairs to normal..ish db range.

If this works...imagine the doors opening not just for hearing but so many diseases. Using a viral vector that can target defects in our DNA is one exciting approach to what are now incurable diseases!

maybe they take this big pump because it's standard FDA approved, the smaller new pump from Draper Lab
might be in it's developement stage or not FDA approved now, but maybe with time, it might be less invasive.
So maybe that's a sign that they go ahead soon...

Indeed, it's quite impressive the adenovirus approach.

 

[tomytl]

Hair Cell Regeneration and Tinnitus
http://www.ata.org/ata-works/sac

Hinrich Staecker, Ph.D., M.D., University of Kansas
Hair Cell Regeneration in a Rat Tinnitus Model
Department of Defense (DoD) grant: $1,272,460; Roadmap Path C
Current data suggests that it is the loss of sensory cells in the inner ear, called hair cells, that leads to this aberrant brain activity. Thus, if lost hair cells could be replaced, restoration of normal brain activity and reduction in tinnitus activity may occur. Dr. Staecker is working to regenerate these sensory hair cells inside the ear. Upon noise trauma, these hair cells and cause hearing loss, thus triggering tinnitus. Current data suggests that the loss of sensory cells in the inner ear lead to the abnormal brain activity associated with tinnitus. The study will determine if hair cell replacement mitigates tinnitus and if it restores normal brain activity to the hearing centers of the brain. Dr. Staecker's work will represent the first investigation of the effects of hair cell regeneration in the brain and could lead to a major breakthrough in tinnitus research.

 

[JohnG]

There are many veterans from Iraq and Afghanistan that have hearing loss and Tinnitus. The DoD is pumping money into it. That is how GenVec got money at first. I guess it takes a bunch of wounded vets to finally get attention and research money. I know my high freq loss was due to guns and explosions. Even if you try to wear protection, you sometimes can't.

 

[James White]

Some realistic news from Dr. Heller from this week :
https://hearinglosscure.stanford.ed...l-like-cells-from-human-embryonic-stem-cells/

 

[tomytl]

Some realistic news from Dr. Heller from this week :
https://hearinglosscure.stanford.ed...l-like-cells-from-human-embryonic-stem-cells/

Hi James,

thanks for sharing. I read this article too, and it looks that HCR through stem cells is some more futuremusic.
I think it's a very valuable research, but far away for use in a human cochlea.
For HCR or hair cell repair, maybe other ways are more applicable. But we never know.
If they can grow and connect hair cells from scratch, this would be indeed amazing.


Greets
tomytl

 

[tomytl]

A new Genvec Annoucement:
http://ir.genvec.com/phoenix.zhtml?c=124130&p=irol-newsArticle&ID=1910811&highlight=


Greets tomytl

 

[rickycyh]

Hi, I got mild hearing loss at 8K Hz with high pitched T, based on what you guys discussed, hearing aid can help cancel the sound without using any masking sound like white noise? all hearing aid have such function? thx....