Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Beste]

Just sent a couple of mails to the stem cells clinics you guys mentioned above. The Australian one contains Turk doctors like me.(I'm no doc, just a regular Turkish girl) This got me thinking if they have any relation to Turkish clinics over here. In Turkey, they just built recently very huge stem cell clinic in my city. I think I can go and talk about tinnitus with them.

Guys, is there any complete list of tinnitus clinics mail adresses you have? We ALL should send messages to them.

 

[Anonymous2929]

That's so interesting you say that Anonymous2929. So interesting. It's crazy how I'm experiencing exactly how you describe what you are picking up through the use hearing aids since they are made to amplify sound/frequencies into your inner ear. What exactly were you diagnosed with by audiologists when you were younger? I see you put down sensorineural hearing loss. It just makes me insanely curious about how your auditory properties are working as one who was born with a hearing loss. You already have trouble hearing to begin with, then when you amplify noise into your inner ear through your hearing aids, it seems like you can't process noise when louder noises are introduced. Wind noise in the car or loud refrigerators at work. It's just so fascinating that I'm experiencing exactly those sort of examples. A fan running in the kitchen blocks my ability to process noises I focus on or the water from a sink running does the same. Wind blowing in my car as I drive down the road trying to hear the radio blocks my ability to process what's being said or played in a song. Processing. Processing. Processing. I wasn't diagnosed with any sort of decibel loss with my audiograms yet now I'm experiencing actually what you described as someone born with what I presume was hearing loss due to lack of hair cell function? Am I right Anonymous2929?

Hello Nick. I was born premature, about 4 weeks early. I was diagnosed with moderate hearing loss at the age of 6 just in my left ear. I was given an BTE aid but I never worn it. But my speech did struggle. I couldn't pronounce certain words such as snake. I took speech therapy for a few years which resolved my my speech problem.

From the age of 6 to 16 I always had a hearing test annually. No hearing loss in right ear and moderate loss in left ear. Never had a problem understanding speech either looking at the person or looking away. But I can say the volume was not much.

When I was 13 I had glue ear in my right ear. Hospital said it is an severe case of inner ear infection. I had a small surgery to place a grommet. This cleared the ear but I noticed few years down the line, I had trouble listening/understanding via my right ear.

So at 16 I had an random hearing test which showed both ears where at moderate loss. This is when I brought my first aid for my right ear. And what a difference. The aid actually helped in understanding speech and made everything much clearer

3 years ago I lost my right ear. It became profound. I truly believe this was due to the inner ear infection which slowly has destroyed all hearing in my right ear. Why I believe this? Because my hearing loss in my left has stayed the same since birth.

Only 3 years ago I started using hearing aid in my left ear. Please note I haven't used an aid in my left ear ever and whilst using the aid, I still don't have a problem with all sounds.

I do have the same problem as you such as processing. But it is only very loud sounds. I don't have a problem say a fan in the kitchen with water running. I find them very natural. I just problems with understanding speech and in the bloody car. But I noticed the newer the car, the more soundproof it is, the better for my hearing. I drive 2003 ford focus and the sound proofing is terrible

I think Nick, for my deafness I am doing really well. The NHS told me for my hearing only a BTE aid will help due to its size and power capability. But you don't want power! You want clarity, that softness which you can perceive as "natural". That is why I alway purchase my aids from the private sector. My current aid is Starkey CIC Z Series. Maybe you can research the aid?

 

[Anonymous2929]

I also have very bad tinnitus in my right ear. Even though my right ear is profound. And funny thing is my tinnitus does not bother me. Most people here research about an cure for tinnitus. A cure for tinnitus will come if there is a cure for hearing loss. All of these hogus bogus stem clinics offering you hope are not genuine

 

[Beste]

Macquarie Stem Cell Clinic just sent an answer to me

"Hi Beste,
Tinnnitus usually responds well, we have observed good improvements in the past. Are you close to us? We are located in Liverpool NSW.

If so, the best step is to come in and have a consultation."

Too bad for me that I live in Turkey.

 

[Stefan K]

Macquarie Stem Cell Clinic just sent an answer to me

"Hi Beste,
Tinnnitus usually responds well, we have observed good improvements in the past. Are you close to us? We are located in Liverpool NSW.

If so, the best step is to come in and have a consultation."

Too bad for me that I live in Turkey.

I am from Australia, I might look into this clinic and see what kind of treatment they offer.

 

[tomytl]

http://journals.lww.com/thehearingj...apy_to_Counteract_Human_Deafness_Draws.1.aspx

 

[RB2014]

http://journals.lww.com/thehearingj...apy_to_Counteract_Human_Deafness_Draws.1.aspx

This is crazy good news. I just wanted to highlight the best part.

So we can deliver the correct gene now back to 80-90% and we are getting much more complete recovery – almost back to normal hearing level. We've made huge progress in the last year. Mice are jumping all over the place…"

It will still take some time to bring this to the human world. The gene therapy will be used in pig and/or monkey ears, as well as in human ear tissue harvested from biopsies. When safety has been fully demonstrated, it will move into the human sector – likely at least five years from now.

 

[Beste]

This is crazy good news. I just wanted to highlight the best part.

So we can deliver the correct gene now back to 80-90% and we are getting much more complete recovery – almost back to normal hearing level. We've made huge progress in the last year. Mice are jumping all over the place…"

It will still take some time to bring this to the human world. The gene therapy will be used in pig and/or monkey ears, as well as in human ear tissue harvested from biopsies. When safety has been fully demonstrated, it will move into the human sector – likely at least five years from now.

Five years is nothing compared to "go and live with it" : )

 

[Pleasure_Paulie]

I am from Australia, I might look into this clinic and see what kind of treatment they offer.

I am from Australia as well. Here is an information pack they will send you. I have emailed them anyway.

http://www.macquariestemcells.com/wp-content/uploads/2015/06/macquarie-stem-cells-info-v4.pdf

 

[Reinier]

I agree. Looks like excellent news.
I am somewhat confused though.
This is to reverse hereditary deafness. But if I am correct these tools can also be used for "acquired" hearing loss?
It focusses on the genetics of hearing loss.
I understand that this master gene ATOH1 is able to turn supporting cells into hair cells by cell differentiation. But you don't want to loose the supporting cell.
This is from Action On Hearing Loss:
Quote: Current gene therapy approaches to restore hearing target Atoh1, which is necessary to produce hair cells. In 2014, the first clinical trial testing this approach started in the USA. The results of the trial are expected next year. There are doubts about how successful this approach will be, as it relies on turning existing supporting cells into hair cells. However, in the mammalian inner ear, supporting cells don't replace themselves, so turning them into hair cells will deplete their numbers. Running out of supporting cells is likely to affect hearing, possibly by changing the structure of the inner ear, or by affecting how the hair cells work, and may ultimately affect how well the gene therapy works. It may be, therefore, that a gene therapy to restore hearing will need to target other genes as well as Atoh1 to be completely successful. But as of now, we don't know which other genes would be best to target, as we don't know enough about how hair cells and supporting cells develop. End quote.
This is also mentioned in the Hearing Journal article. There is also talk of another gene.
Quote:
THOSE JUMPING MICE

One of the targeted gene types is called TMC1, which encodes key protein for converting molecular stimulus of sound into an electrical signal transmitted to the brain allowing for hearing. There are 40 different mutations in TMC1 that cause deafness in humans. End quote.
I don't understand this. Has this got anything to do with hair cells? What is being regenerated in the inner ear?

But I do hope that this research puts more pressure on other (commercial) researchers. Who will win?

 

[Nick Pyzik]

I agree. Looks like excellent news.
I am somewhat confused though.
This is to reverse hereditary deafness. But if I am correct these tools can also be used for "acquired" hearing loss?
It focusses on the genetics of hearing loss.
I understand that this master gene ATOH1 is able to turn supporting cells into hair cells by cell differentiation. But you don't want to loose the supporting cell.
This is from Action On Hearing Loss:
Quote: Current gene therapy approaches to restore hearing target Atoh1, which is necessary to produce hair cells. In 2014, the first clinical trial testing this approach started in the USA. The results of the trial are expected next year. There are doubts about how successful this approach will be, as it relies on turning existing supporting cells into hair cells. However, in the mammalian inner ear, supporting cells don't replace themselves, so turning them into hair cells will deplete their numbers. Running out of supporting cells is likely to affect hearing, possibly by changing the structure of the inner ear, or by affecting how the hair cells work, and may ultimately affect how well the gene therapy works. It may be, therefore, that a gene therapy to restore hearing will need to target other genes as well as Atoh1 to be completely successful. But as of now, we don't know which other genes would be best to target, as we don't know enough about how hair cells and supporting cells develop. End quote.
This is also mentioned in the Hearing Journal article. There is also talk of another gene.
Quote:
THOSE JUMPING MICE

One of the targeted gene types is called TMC1, which encodes key protein for converting molecular stimulus of sound into an electrical signal transmitted to the brain allowing for hearing. There are 40 different mutations in TMC1 that cause deafness in humans. End quote.
I don't understand this. Has this got anything to do with hair cells? What is being regenerated in the inner ear?

But I do hope that this research puts more pressure on other (commercial) researchers. Who will win?

This is great work. Definitely has moved some gears for research with deafness. My perspective though, is that anyone who acquired hearing loss from acoustic trauma will most likely benefit the best from repairing their inner ear to their brain mechanisms. Hidden Hearing loss is much more prevalent than thought. Hearing is all processing. If your brain can't process a frequency because it's getting lost in the mix of several other frequencies your sensory hair cells are picking up, then it's not going to "hear" that frequency. Especially the higher frequencies. These are the closest to the front of the cochlea, and the first to lose nerve fibers to.

Those times you've gone to a concert or a loud event and came out with ringing in your ears for the night or the next day or two. Those were nerve fibers lost. Not "Temporary Hearing Loss". That's pretty scary to think about. It happened a lot to me through the past decade.

 

[cornelius]

This is great work. Definitely has moved some gears for research with deafness. My perspective though, is that anyone who acquired hearing loss from acoustic trauma will most likely benefit the best from repairing their inner ear to their brain mechanisms. Hidden Hearing loss is much more prevalent than thought. Hearing is all processing. If your brain can't process a frequency because it's getting lost in the mix of several other frequencies your sensory hair cells are picking up, then it's not going to "hear" that frequency. Especially the higher frequencies. These are the closest to the front of the cochlea, and the first to lose nerve fibers to.

Those times you've gone to a concert or a loud event and came out with ringing in your ears for the night or the next day or two. Those were nerve fibers lost. Not "Temporary Hearing Loss". That's pretty scary to think about. It happened a lot to me through the past decade.

After not having been believed by all those "physicians", that would be justice, but does research target mixed hearing loss therapies as well ? Because there are many noise injured - in addition to nerve damage - who seem to have significant hair cell loss too. Hopefully no agreement between hearing aid dealers and stem cells providers

 

[XDR]

Macquarie Stem Cell Clinic just sent an answer to me

"Hi Beste,
Tinnnitus usually responds well, we have observed good improvements in the past. Are you close to us? We are located in Liverpool NSW.

If so, the best step is to come in and have a consultation."

Too bad for me that I live in Turkey.

Snake oil, there are a lot of Cowboy clinics, don't go near it.

Taking fat and re-injecting it back into is not research or valid science. I'd wait for definitive proof, best case you've lost a lot of money, worse you get a condition much worse.

there is research in the fields from real doctors and real universities, using real Gene Therapy.
http://www.med.kyoto-u.ac.jp/en/organization-staff/research/doctoral_course/r-055/

 

[Reinier]

med.kyoto-u.ac.jp/en/organization-staff/research/doctoral_course/r-055/
Interesting quote:
Clinical application is now available for regeneration of inner ear using drug delivery system
End quote.
I assume this is for acute sensorineural hearing loss? In the last 6 months I have seen so many clinics, companies and universities that are conducting research in this area that I don't remember seeing the Kyoto university. I stored the short-cut.

Those times you've gone to a concert or a loud event and came out with ringing in your ears for the night or the next day or two. Those were nerve fibers lost.

I agree. I think, ringing after noise is always extra wear in or around the inner ear.

but does research target mixed hearing loss therapies as well ? Because there are many noise injured - in addition to nerve damage - who seem to have significant hair cell loss too.

After reading all the documents and my personal experience it is my believe that you start with nerve damage. This loss can leave you more prone to not understanding people in noisy environment and even tinnitis and/or hyperacusis. This does not show up on your audiogram. Not the total range is checked, and it is only a hearing threshold that is checked.
When noise damage progresses I think hair cells cease to function (die?). This does show up on an audiogram.

There must be a good reason that Stanford, Action On Hearing Loss, Hearing Health Foundation, and many more have not changed there research drastically. Hair cell regeneration is still high on their agenda.

But I don't think there is reason for a discussion hair cell loss versus nerve damage.
I think people that have an audiogram that indicate hearing loss (and that number is pretty high) will have nerve damage and hair cell loss. When you get older without noise incidents or other inner/middle ear damage, hearing "wears" anyway. I think there is one obvious difference between NIHL and normal wear and tear.
NIHL (also ototoxicity) you can ascribe to events/incidents etc... and is faster than age related hearing loss.
My damaged ear shows a loss that is equal to the hearing of a 80 year old person. My ear "aged" 30 years in a few milliseconds!

I also understand research showed that regenerated hair cells connect to nerves again. Which I think is pretty amazing!

 

[whiskeykonteq]

Snake oil, there are a lot of Cowboy clinics, don't go near it.

Taking fat and re-injecting it back into is not research or valid science. I'd wait for definitive proof, best case you've lost a lot of money, worse you get a condition much worse.

there is research in the fields from real doctors and real universities, using real Gene Therapy.
http://www.med.kyoto-u.ac.jp/en/organization-staff/research/doctoral_course/r-055/

Then how do you explain this:
https://clinicaltrials.gov/ct2/show/NCT02038972
based on this study:
http://www.ncbi.nlm.nih.gov/pubmed/18819255

Point is, there is something you can do while you wait for definite proof ;-)

Cheers

 

[Pleasure_Paulie]

Snake oil, there are a lot of Cowboy clinics, don't go near it.

Taking fat and re-injecting it back into is not research or valid science. I'd wait for definitive proof, best case you've lost a lot of money, worse you get a condition much worse.

They charge $9,000AUD. Thats about $12 for people with US currency. haha!

 

[Reinier]

They charge $9,000AUD. Thats about $12 for people with US currency. haha!

If that where only true.
I still would hesitate though. I don't want some irreversible health issue(s) on top of hearing problems. I will just continue reading documents for now. and save money.
http://www.ncbi.nlm.nih.gov/pubmed/18819255
This is from 2008! Why is there no follow up? Or is it so complicated that this is what it takes to get practical improvements in humans? Probably both.
Perhaps we can regard the clinical trial at the hospital in Orlando as a follow up?

 

[tomytl]

Hi,
I think all these stem cell therapies offered by some clinics now aren't likely to help hearing injured people.
If researchers would have results with such a simple approach, why should they spend milions in further gene therapy research?
I think, it's far more complicated to bring any nerves to regrow again who actually lost their ability to regrow, as it's unfortunately with the hearing cells called hair cells and the underlying connection network.

It's like with many alternative treatments, they sound plausible and their logic is based on seriouse science, but their promise of treatment is happening in the range of speculation and not reproducable...

If there would be a causal, effective treatment I would think we would know.

And if there were treatments offered by some nice people who really would like to help us, why should they take soooo much money from us?

 

[Mario martz]

Me Too, i had that ringing in my ears many, many times after a festival, gig or concert.
never did something about it, since i was told "it was normal" lol.
a lot of my friends have told me "hey this has happend to me after a concert too"
and with the current concert/festival fever... i guess many many tinnitus cases are gonna appear in the next 5 years.

 

[RB2014]

Then how do you explain this:
https://clinicaltrials.gov/ct2/show/NCT02038972
based on this study:
http://www.ncbi.nlm.nih.gov/pubmed/18819255

Point is, there is something you can do while you wait for definite proof ;-)

Cheers

Both of those studies were done with cord blood and not blood extracted from fat, processed, and then re-injected into the individual with an iv. I don't think its anywhere near the same thing. The cells they both produce are different.
From what I read I think if you are using the fat cells, they have to be modified to become the inner ear hair cells and then re-injected directly into the ear. I'm not sure if there are any studies where using that method has gained anyone any hearing.

 

[whiskeykonteq]

Both of those studies were done with cord blood and not blood extracted from fat, processed, and then re-injected into the individual with an iv. I don't think its anywhere near the same thing. The cells they both produce are different.
From what I read I think if you are using the fat cells, they have to be modified to become the inner ear hair cells and then re-injected directly into the ear. I'm not sure if there are any studies where using that method has gained anyone any hearing.

There were not studies but there were cases - one of them being Australian guy called Francis that got ~ 25 db from adipose (fat) derived stem cells, another case is Chloe that got 40 - 50 db (also got MSCs from adipose). Also 2 cases from Australian clinic that had tinnitus completely resolved after getting fat derived stem cells. And not to forget our own @FERNANDO GIL that got improvement in tinnitus after getting therapy of adipose MSCs.
Also if you don't believe that fat derived stem cells can help, you can always go for umbilical cord blood donated MSCs and have same thing as those kids in above mentioned clinical trial. So after all, I still think that there is something we can do while waiting for definitive proof.

N.B. As far as I know, no one believes that MSCs can become new hair cells, ribbon synapses of SGN, or VIII cranial nerve. But what I'm counting on is MSCs immunomodulatory, anti-inflammatory and antiapoptotic properties. i.e they should help organism to heal itself and reverse hair cells / SGN's cells apoptosis. That's why adipose cells works too (at least in some cases).

Cheers

 

[XDR]

med.kyoto-u.ac.jp/en/organization-staff/research/doctoral_course/r-055/
Interesting quote:
Clinical application is now available for regeneration of inner ear using drug delivery system
End quote.
I assume this is for acute sensorineural hearing loss? In the last 6 months I have seen so many clinics, companies and universities that are conducting research in this area that I don't remember seeing the Kyoto university. I stored the short-cut.

Yes acute sensorineural hearing only at this stage. I'm going to try this myself using HGH or IGF1 if I can get a hold of it.

med.kyoto-u.ac.jp/en/organization-staff/research/doctoral_course/r-055/

After reading all the documents and my personal experience it is my believe that you start with nerve damage. This loss can leave you more prone to not understanding people in noisy environment and even tinnitis and/or hyperacusis. This does not show up on your audiogram. Not the total range is checked, and it is only a hearing threshold that is checked.

Actually I'm starting to think tinnitis and hyperacusisis cause by defects in the veins and arteries. I'll write up my full thoughts and reasoning in another thread but in short I think a three step process.

1. Damage to veins and arteries through trama (infection, injury).
2. asphyxiation of inner ear cell causing hearing loss.
3. resulting Tinnitus is "water hammer" or "blood hammer" with the damaged vein flowing too much blood into the damaged ear. Causing a high pitch noise simliar to water hammer in pipes. Of which T suffers (inclduing me) can manipulate the pitch and intensity of by affecting their blood flow directly (medication) or indirectly (eg flying, hypebartic chambers).

From what I can see, treatment is two stage. 1. hearing loss via Gene Therapy when its developed, 2. Tinnutus would have to be surgical to add a stint (or something mechanical to adjust flow) to moderate blood flow inside the ear.

Both of those studies were done with cord blood and not blood extracted from fat, processed, and then re-injected into the individual with an iv. I don't think its anywhere near the same thing. The cells they both produce are different.

From what I read I think if you are using the fat cells, they have to be modified to become the inner ear hair cells and then re-injected directly into the ear. I'm not sure if there are any studies where using that method has gained anyone any hearing.

This, just because it has a label of something credible does not mean it actually works. Think of all the diet supplement industry. Just because its called "Gene Therapy" it doesn't mean what they are doing is anything credible.

Dont get me wrong I think Gene therapy once developed will work, but that Australian clinic is snake oil. If it was a cure they would of won the Noble prize by now and be used in Hospitals.

I live in Australia, the medical cowboy clinics here are quite unregulated, been the cause of a lot of damage and lot of wild claims, stay away until you see hospitals using it.

 

[Reinier]

1. Damage to veins and arteries through trama (infection, injury).

In my own personal experience (very high impulse sound level) I would regard damage to hair cells and/or connections to these hair cells more likely.
The reason being that hair cells get pretty much the full grunt of a sound explosion or prolonged high sound levels.
They are the first "weak" link, together with hair cell connections, in the inner ear. Especially the first section of the cochlea (high and middle frequencies) will be hardest hit.
Just a thought.

 

[XDR]

In my own personal experience (very high impulse sound level) I would regard damage to hair cells and/or connections to these hair cells more likely.
The reason being that hair cells get pretty much the full grunt of a sound explosion or prolonged high sound levels.
They are the first "weak" link, together with hair cell connections, in the inner ear. Especially the first section of the cochlea (high and middle frequencies) will be hardest hit.
Just a thought.

I think damage to all; nerves, veins and arteries. Cochlea is basically an air balloon that converts air pressure to sound. Overload it, the balloon and supporting systems are damaged, get a stuff signal. Much like a oil pressure sensor on a car.

This is all my theory though and making a treatment for myself on this assumption.

 

[Pleasure_Paulie]

Another company - http://www.brisbaneregeneration.com.au have told me they have treated a patient for tinnitus recently.

Most be of us for us other Australian peeps.

 

[GregCA]

Another company - http://www.brisbaneregeneration.com.au have told me they have treated a patient for tinnitus recently.

Did you ask what the outcome was?

 

[Pleasure_Paulie]

Did you ask what the outcome was?

I've now emailed a bunch of clinics around Australia, and it seems only Macquarie (http://www.macquariestemcells.com) have done it a few times with supposed successful outcomes at $9,000AUD, And Brisbane Regeneration (http://www.brisbaneregeneration.com.au) have recently treated somebody, but they won't sure of success as it was "too early to tell" at $4500AUD.

Both clinics appear to use your own cells (Fat) via liposuction.

 

[Reinier]

What percentage of the inner ear workings actually do we know?
http://www.medicalnewstoday.com/releases/311584.php

 

[tomytl]

news on atoh1 research
http://www.eurekalert.org/pub_releases/2016-07/uosc-usc070116.php

 

[Mario martz]

news on atoh1 research
http://www.eurekalert.org/pub_releases/2016-07/uosc-usc070116.php

you always have great updates!