Inner Ear Hair Cell Regeneration — Maybe We Can Know More

#1,414
Nick, have you thought about reaching out to Amanda, one of the other participants in the Novartis trial. I remember a while back looking at her facebook page which was linked in one of the threads.
 
#1,415
I'd like to ask why researchers state that it's the sensory hair cell death inside a human's cochlea(s) that cause hearing loss? Why has there been research, most specifically by those of the Harvard Medical School, displaying absolutely zero sensory hair cell loss while a visible large percentage of nerve synapses were lost.

It's so confusing why we as humans are pursuing sensory hair cells so much. Is it because of the simple understanding that animals can regenerate these sensory cells after damage?
 
#1,416
RB2014 said:
Nick, have you thought about reaching out to Amanda, one of the other participants in the Novartis trial. I remember a while back looking at her facebook page which was linked in one of the threads.
Click to expand...
RB,

I remember I did try to find Amanda on Facebook back while I was on the hunt in December. I wasn't able to find her after several attempts. Jeff Bricker did mention "in the case of a few other lab rats", so he must have spoken to other members of the trial. I was speaking to Jeff yesterday about how things were going with his Cochlear Implants. Here's our conversation:

Me: Awesome. How have things been with the Cochlear Implants? I read your post about being able to hear all the cattle in the fields you work at. How has it been in noisy areas like restaurants?

Jeff: Waiting to check out the bar scene soon. Music has actually sounded decent for the most part, especially instrumental songs.

Me: That's great! Do you feel like a robot a little bit? Does everything sound a bit metallic to you?

Jeff: There is a bit of a metallic sound depending upon whether it is a high or low frequency sound. Lower base guitar sounds and drums almost sound normal at this point, keyboards too. Lower voices are almost normal too. Higher female voices and higher frequency sounds are the most metallic as I haven't heard them in years. It will take a few months for my brain to comprehend all of it but I am pleased with the improvement in understanding speech so far

Me: That's incredible Jeff. Now let's just hope your ability to process sounds in noisy areas is okay.

Jeff: That will be the next big test. A noisy restaurant or a bar with a band playing are my next choices

Me: Let me know how that goes if you want!

Jeff: Will do

(End Conversation)

If there is anything you or anyone else would want me to ask Jeff, just let me know! He seems like a really nice man just from talking through Facebook.
 
#1,417
Nick Pyzik said:
I'd like to ask why researchers state that it's the sensory hair cell death inside a human's cochlea(s) that cause hearing loss? Why has there been research, most specifically by those of the Harvard Medical School, displaying absolutely zero sensory hair cell loss while a visible large percentage of nerve synapses were lost.

It's so confusing why we as humans are pursuing sensory hair cells so much. Is it because of the simple understanding that animals can regenerate these sensory cells after damage?
Click to expand...
The thing is though Nick how do we regenerate these synapses?Ive seen so many hope lifting articles involving Neurotrophins etc but still no commited research to the problem.Apparently after haircell regeneration occurs new nerve and synapse connections are established also so I can imagine it not being too hard to initiate nerve growth in a cochlea with intact haircells but of course I make it sound a lot easier than it truly is
 
#1,419
Nick Pyzik said:
It's so confusing why we as humans are pursuing sensory hair cells so much. Is it because of the simple understanding that animals can regenerate these sensory cells after damage?
Click to expand...
The way I see it at the moment: It started with the discovery that birds regenerate damaged hearing. I don't know if at that time it was understood that it was haircell regeneration or a combination. Haircell regeneration and regenerating/reconnecting synapses.

So the loss of synapses with surviving hair cells is perhaps just better understanding of the whole process of hearing loss.

I personally can understand and relate to the findings that the synapses for higher sound levels have lost connection to hair cells. So the audiogram is OK and yet you have difficulty understanding people in noisy environments (and tinnitus?). But I also can understand that with more pronounced hearing loss (which does show on an audiogram) there is hair cell loss.
 
#1,420
Reinier said:
The way I see it at the moment: It started with the discovery that birds regenerate damaged hearing. I don't know if at that time it was understood that it was haircell regeneration or a combination. Haircell regeneration and regenerating/reconnecting synapses.

So the loss of synapses with surviving hair cells is perhaps just better understanding of the whole process of hearing loss.

I personally can understand and relate to the findings that the synapses for higher sound levels have lost connection to hair cells. So the audiogram is OK and yet you have difficulty understanding people in noisy environments (and tinnitus?). But I also can understand that with more pronounced hearing loss (which does show on an audiogram) there is hair cell loss.
Click to expand...
But how do we know if that increased hearing loss is not just due to an increased amount of out-going nerve fibers connected to the still-remaining sensory hair cells?

I understand that researchers have been able to create new established connections between the new sensory hair cells and the auditory cortex, but there are issues to that. 1) This will not solve any ringing issues we have. 2) Too many sensory hair cells will cause more hearing trouble. 3) The nerve fibers/spiral ganglion neurons that form with these new hair cells need to be a specific type of the nervous system or else the subject will still have trouble hearing.
 
#1,421
GregCA said:
Did Jeff have T prior to the CI? Did the CI change anything T-wise?
Click to expand...
Greg,

I don't recall Jeff talking about having ringing at all. Here is part of my conversation with him regarding how he developed his hearing loss.

(12/09/15) 6:26PM
Me: Jeff, how is it going?

I was interested in how your Novartis hearing treatment went and if you have had any improvement over time? I apologize for coming out of nowhere with this facebook message but I'm on a mission to see how well the CGF166 clinical trial treatments are going so far.

I have had hearing issues for a good few months now and was looking to come in contact with Novartis regarding their clinical trials.

How long have you had a hearing issue in your life? I'd like to read about it.

Jeff: Hi Nick,

I first started losing my hearing when I was about 12 years old. By the time I went to college it was becoming a serious problem. Both of my brothers have the same problem and my niece is now down to 25% hearing. I have about 5% left. I had the surgery back in May and just completed my last monthly checkup for the trial. I won't be check again until May.

As far as the results go, I'm told that my progress has been the slowest of the group of 7 patients so far, however, some of the others are experiencing the same issues as myself. We have picked up some new frequencies of sound but our brains have yet to translate a lot of it into speech recognition, which was the main focus of the trial so that hearing aids would be more effective. Turns out that the whole process will take longer than they anticipated.

If you think you might want to be a test subject they are looking for more people. Just log onto their website and follow the links for a test application. You will need to send a current audio gram in with the application. If you have any more questions, feel free to contact me.

Best Wishes,

Jeff

(End Conversation)


I just messaged Jeff now asking if he ever had ringing in his ears growing up or around present time. I'll let you know what he replies back.
 
#1,422
bill 112 said:
The thing is though Nick how do we regenerate these synapses?Ive seen so many hope lifting articles involving Neurotrophins etc but still no commited research to the problem.Apparently after haircell regeneration occurs new nerve and synapse connections are established also so I can imagine it not being too hard to initiate nerve growth in a cochlea with intact haircells but of course I make it sound a lot easier than it truly is
Click to expand...
I'm still trying to learn what I can about how our brains interpret sound so I can't give a very detailed response back to what you've asked Bill. From what I've read, it seems as though the ringing one hears is due to the loss of spiral ganglion neurons, which I believe were apart of the central nervous system. So the brain can't repair that sort of damage no matter what you feed it. My understanding is that these neurons fall back into the inner regions of the brain and I'm assuming they turn back into brain cells. I feel like if correctly differentiated stem cells were transplanted into the region between the inner ear and the brain as specific spiral ganglion neurons, this would allow a connection to form off from the glial scars that appeared after the damage. This is what Kyoto University had a study on and it showed somewhat pleasant results.

I believe that the method to feed the brain neurotrophic factors + other concoctions along with it, will only work on those that first developed ringing for a few weeks. This is because the newly disconnected nerve fibers and damaged spiral ganglion neurons haven't retracted back deep into the brain.

I wish I could say more, but I don't want to keep stating I believe or from what I've read. This is definitely something I want to work hands on with one day if hearing restoration hasn't made any progress in the future.
 
#1,424
Nick Pyzik said:
I first started losing my hearing when I was about 12 years old. By the time I went to college it was becoming a serious problem. Both of my brothers have the same problem and my niece is now down to 25% hearing.
Click to expand...
So it is genetic hearing loss Jeff suffers from.
I wonder if this does not make it more elusive. Not so "straight forward". Do they know if members of his family have hearing loss because of hair cell loss? I assume that is the case. Otherwise Novartis would not try regenerating hair cells.
 
#1,425
Reinier said:
So it is genetic hearing loss Jeff suffers from.
I wonder if this does not make it more elusive. Not so "straight forward". Do they know if members of his family have hearing loss because of hair cell loss? I assume that is the case. Otherwise Novartis would not try regenerating hair cells.
Click to expand...
He suffers from a genetic hearing loss similar to mine. His has progressed a faster than mine from what I can gather. I remember noticing at approx 16 years old vs he said 12. I think we are born with perfect hearing, but it starts to quickly drop. For me its approx 10db a year for lower frequencies and 20db for the higher frequencies every 10 years or so.
I also subscribe to his niece's website. She also has the same defective gene as Jeff. I have seen her audiograms and it is a ski slope pointing downward starting a 0 at the beginning to -100db+ at 8k.
We are all guessing but the other girl Amanda had hearing loss from a swimming incident from what I remember. It was more of a natural loss vs a genetic loss. It could be this formula works on loss associated with normal ageing or a specific event vs a gradual genetic loss.
Novartis knew this going in from what I understand. I remember reading his early entries on his Nieces website and they did do genetic testing and they were very thorough in their questions and testing. They never posted the results anywhere, but I remember her saying the information would be useful to them moving forward.

Nick, I will dig around a bit. I remember hitting her facebook page at one point. I am no longer the social butterfly I once was so I'll let you make contact. thanks.

Jeff may or may not have had T. I had it all my life and only noticed in super complete silence. Since I wore hearing aides it put the frequencies back so my brain never missed them. This kept the T at bay until a couple years ago with a serious problem with anxiety brought the T to the surface. I'm sure without the anxiety it would have postposed it a couple more years until the frequencies get to the -100db point where hearing aides just don't cut it anymore and you can only amplify so much before your ears just so no. Jeff is in his 50s. I'm pretty sure he has it.
 
#1,426
RB2014 said:
He suffers from a genetic hearing loss similar to mine. His has progressed a faster than mine from what I can gather. I remember noticing at approx 16 years old vs he said 12. I think we are born with perfect hearing, but it starts to quickly drop. For me its approx 10db a year for lower frequencies and 20db for the higher frequencies every 10 years or so.
I also subscribe to his niece's website. She also has the same defective gene as Jeff. I have seen her audiograms and it is a ski slope pointing downward starting a 0 at the beginning to -100db+ at 8k.
We are all guessing but the other girl Amanda had hearing loss from a swimming incident from what I remember. It was more of a natural loss vs a genetic loss. It could be this formula works on loss associated with normal ageing or a specific event vs a gradual genetic loss.
Novartis knew this going in from what I understand. I remember reading his early entries on his Nieces website and they did do genetic testing and they were very thorough in their questions and testing. They never posted the results anywhere, but I remember her saying the information would be useful to them moving forward.

Nick, I will dig around a bit. I remember hitting her facebook page at one point. I am no longer the social butterfly I once was so I'll let you make contact. thanks.

Jeff may or may not have had T. I had it all my life and only noticed in super complete silence. Since I wore hearing aides it put the frequencies back so my brain never missed them. This kept the T at bay until a couple years ago with a serious problem with anxiety brought the T to the surface. I'm sure without the anxiety it would have postposed it a couple more years until the frequencies get to the -100db point where hearing aides just don't cut it anymore and you can only amplify so much before your ears just so no. Jeff is in his 50s. I'm pretty sure he has it.
Click to expand...

I spoke to Jeff the other day and he told me he had audible ringing while he was younger. He never noticed it as much later on in his life and hasn't with the Cochlear Implants he has now.

Genetic hearing loss could also mean issues between the brain and the inner ear. If the GenVec did not work on Jeff or other participants, then something is wrong with the understanding that hair cells are what amplify sound into our brain.

I've noticed there are many people either born with hearing loss or like Jeff have developed it as they've grown older where ringing has been involved too. I truly believe it's an issue with the Central Nervous System. A genetic development that didn't work out for someone with hearing loss at birth or as their brain developed as an older child/teen.

The study "Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions" put on by Tanit Ganez Sanchez, Fernanda Moraes, Larry E. Roberts, and more - moves us closer to understanding the ringing many of us hear and also why it affects ones hearing. Just like researchers are focusing on the sensory hair cells, they need to put the same kind of focus on the spiral ganglion neurons. The bi-polar workings of both types I and II are what I believe amplify sound and help us hear better.

My understanding is that if you feed the correct neurotrophic factors, the brain can repair the damages that have taken place, but it can only send out "out-going nerve fibers from the spiral ganglion neurons that are left over. That's where hearing loss takes place. Neurotransmitters at high levels taken into the body/brain can also change the way the brain processes/hears sound. Deplete most of those neurotransmitters in the brain and you will have trouble hearing sound even more.
 
#1,428
Nick Pyzik said:
I spoke to Jeff the other day and he told me he had audible ringing while he was younger. He never noticed it as much later on in his life and hasn't with the Cochlear Implants he has now.

Genetic hearing loss could also mean issues between the brain and the inner ear. If the GenVec did not work on Jeff or other participants, then something is wrong with the understanding that hair cells are what amplify sound into our brain.

I've noticed there are many people either born with hearing loss or like Jeff have developed it as they've grown older where ringing has been involved too. I truly believe it's an issue with the Central Nervous System. A genetic development that didn't work out for someone with hearing loss at birth or as their brain developed as an older child/teen.

The study "Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions" put on by Tanit Ganez Sanchez, Fernanda Moraes, Larry E. Roberts, and more - moves us closer to understanding the ringing many of us hear and also why it affects ones hearing. Just like researchers are focusing on the sensory hair cells, they need to put the same kind of focus on the spiral ganglion neurons. The bi-polar workings of both types I and II are what I believe amplify sound and help us hear better.

My understanding is that if you feed the correct neurotrophic factors, the brain can repair the damages that have taken place, but it can only send out "out-going nerve fibers from the spiral ganglion neurons that are left over. That's where hearing loss takes place. Neurotransmitters at high levels taken into the body/brain can also change the way the brain processes/hears sound. Deplete most of those neurotransmitters in the brain and you will have trouble hearing sound even more.
Click to expand...

This was posted earlier in the thread so I guess you've already seen this?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842978/
 
#1,429
lapidus said:
This was posted earlier in the thread so I guess you've already seen this?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842978/
Click to expand...
I have looked through that. I actually have been taking supplements for numerous months that have Nuerotrophic factors or cellular protective properties. Ashwagandha, Lion's Mane, Cordyceps, Astaxanthin,(found Astaxanthin thanks to another user way back in November of last year).

It's great to see more work being done on the synapses/nerve fibers that are damaged through acoustic trauma. Decibel Therapeutics was said to be focusing on a treatment for that. Here's my input on that though:

Such a treatment will only work in a short period of time. Charles Liberman even stated in an article about loud noise/nerve fiber loss that after only a certain months to a year these nerve fibers will retract back into the brain. In other words, the spiral ganglion neurons and cells involved in those nerve fibers will all degenerate and fall back in to what supposedly would be the brain cells they came from inside the inner regions of the brain.

There's no way such a procedure could grow these damaged parts, which I believe are part of the central nervous system, all the way back into the inner most regions of the inner ear. The damaged mechanisms have to still be residing near the cochleas to be able to re-establish connections. They had those studies where cochlear implants were used to re-grow the damaged auditory nerve. The images of the rat subjects showed their spiral ganglion neurons were still residing near the space between the inner ear and the brain.

I believe differentiated stem cells placed on the formed glial scars of the damaged nerves/neurons is the best possible way to re-establish the damaged auditory pathways in those who have had tinnitus or hearing troubles for a long period of time. A year, a few years, or even decades. Kyoto's studies showed nice results with that type of procedure.
 
#1,431
Nick Pyzik said:
I have looked through that. I actually have been taking supplements for numerous months that have Nuerotrophic factors or cellular protective properties. Ashwagandha, Lion's Mane, Cordyceps, Astaxanthin,(found Astaxanthin thanks to another user way back in November of last year).

It's great to see more work being done on the synapses/nerve fibers that are damaged through acoustic trauma. Decibel Therapeutics was said to be focusing on a treatment for that. Here's my input on that though:

Such a treatment will only work in a short period of time. Charles Liberman even stated in an article about loud noise/nerve fiber loss that after only a certain months to a year these nerve fibers will retract back into the brain. In other words, the spiral ganglion neurons and cells involved in those nerve fibers will all degenerate and fall back in to what supposedly would be the brain cells they came from inside the inner regions of the brain.

There's no way such a procedure could grow these damaged parts, which I believe are part of the central nervous system, all the way back into the inner most regions of the inner ear. The damaged mechanisms have to still be residing near the cochleas to be able to re-establish connections. They had those studies where cochlear implants were used to re-grow the damaged auditory nerve. The images of the rat subjects showed their spiral ganglion neurons were still residing near the space between the inner ear and the brain.

I believe differentiated stem cells placed on the formed glial scars of the damaged nerves/neurons is the best possible way to re-establish the damaged auditory pathways in those who have had tinnitus or hearing troubles for a long period of time. A year, a few years, or even decades.
Click to expand...
So the only way to regrow these connections is by Stemcells or am I missing something?Is it possible to sprout new connections at all or is it an impossibility?I have T and H for a number of years now making any supplements pretty much useless at this stage I guess,but is it possible to sprout new connections from the CNS to the inner ear?
 
#1,433
Nick Pyzik said:
I have looked through that. I actually have been taking supplements for numerous months that have Nuerotrophic factors or cellular protective properties. Ashwagandha, Lion's Mane, Cordyceps, Astaxanthin,(found Astaxanthin thanks to another user way back in November of last year).

It's great to see more work being done on the synapses/nerve fibers that are damaged through acoustic trauma. Decibel Therapeutics was said to be focusing on a treatment for that. Here's my input on that though:

Such a treatment will only work in a short period of time. Charles Liberman even stated in an article about loud noise/nerve fiber loss that after only a certain months to a year these nerve fibers will retract back into the brain. In other words, the spiral ganglion neurons and cells involved in those nerve fibers will all degenerate and fall back in to what supposedly would be the brain cells they came from inside the inner regions of the brain.

There's no way such a procedure could grow these damaged parts, which I believe are part of the central nervous system, all the way back into the inner most regions of the inner ear. The damaged mechanisms have to still be residing near the cochleas to be able to re-establish connections. They had those studies where cochlear implants were used to re-grow the damaged auditory nerve. The images of the rat subjects showed their spiral ganglion neurons were still residing near the space between the inner ear and the brain.

I believe differentiated stem cells placed on the formed glial scars of the damaged nerves/neurons is the best possible way to re-establish the damaged auditory pathways in those who have had tinnitus or hearing troubles for a long period of time. A year, a few years, or even decades. Kyoto's studies showed nice results with that type of procedure.
Click to expand...

So basically you are saying that these therapies of regrowing hair cells work for chickens because the hearing loss was recent. It won't work for someone that has had hearing loss for a long time?

So we are really looking for a stem cell treatment and not a chemical that will regrow the hair cells for someone with long term hearing loss like Jeff?

Is it possible in time these connections could get re-established? I guess it doesnt seem like they will since Jeff did give it quite a bit of time and nothing came out of it.
 
#1,434
RB2014 said:
So basically you are saying that these therapies of regrowing hair cells work for chickens because the hearing loss was recent. It won't work for someone that has had hearing loss for a long time?

So we are really looking for a stem cell treatment and not a chemical that will regrow the hair cells for someone with long term hearing loss like Jeff?

Is it possible in time these connections could get re-established? I guess it doesnt seem like they will since Jeff did give it quite a bit of time and nothing came out of it.
Click to expand...
I'm stating that acoustic trauma to ones hearing is most likely not hair cell damage like these foundations/researchers are displaying. It just doesn't make sense that certain researchers would find that a measurably loud db level would cause zero hair cell loss in an animal subject, but yet a large loss of nerve synapses in present time and as time moves on. How does such an occurrence happen with some researchers and then others somehow found that lost sensory hair cells were the cause of hearing issues in the animal subjects?

The ringing you hear and many others hear, is currently being linked to spiral ganglion neuronal damage. Now this is where I can't really use my "I believe" or "what I think" sort of talk. I need to actually study and read from textbooks about our auditory system to understand which spiral ganglion neuron (type I or II) is involved in neurotransmissions or which one is referred to simply as in-going or out-going like those from Johns Hopkins University have talked about.

Jeff stated that he had ringing when he was younger, but somehow it just magically dissapeared overtime. There are two scenarios to that. There was either neuronal/brain cellular death that caused the ringing to cease or his brain has used its plasticity along side the neurotransmitters Jeff is taking in, to get around this auditory system malfunction.

Here's my understanding. We are either born with the specific spiral ganglion neuronal connections to our brain that allow us to process sound as a higher level than others because of the neurotransmitting properties associated with it or we aren't. Or you're genetically born with or develop the defect of this malfunctioning auditory property that causes you to have hearing loss. That's why some people develop ringing after loud events and then you have those friends/family/relatives you've asked that have never experienced ringing in their ears.

Right now, time is our only real answer though. We'll see what happens with these hair cell generating therapies being tested. We've witnessed one botch already with Jeff and a few other participants like he stated.
 
#1,437
Nick Pyzik said:
It's great to see more work being done on the synapses/nerve fibers that are damaged through acoustic trauma. Decibel Therapeutics was said to be focusing on a treatment for that. Here's my input on that though:

Such a treatment will only work in a short period of time. Charles Liberman even stated in an article about loud noise/nerve fiber loss that after only a certain months to a year these nerve fibers will retract back into the brain.
Click to expand...

When I mailed Liberman asking about therapeutic window for neutrophins to be effective his answer was not as strict, he said:
"Unfortunately, we really just don't know yet. The science behind all this is still being done!"

It seems they are not in a position yet to state it will be effective up to 1 year only from the onset
 
#1,438
Nick Pyzik said:
Such a treatment will only work in a short period of time. Charles Liberman even stated in an article about loud noise/nerve fiber loss that after only a certain months to a year these nerve fibers will retract back into the brain. In other words, the spiral ganglion neurons and cells involved in those nerve fibers will all degenerate and fall back in to what supposedly would be the brain cells they came from inside the inner regions of the brain.
Click to expand...
What I do not understand than is why cochlear implants are still able to work, even after decades? (Jeff had hearing loss for a long time and I understand he is detecting high frequencies again).
Also in this article (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842978/) I read that that the reason that cochlear implants can still work after many years must be because of the long time surviving neurons. In order to make use of a cochlear implant you need it to get the signals from this implant to your brain.
Quote: Given that cochlear implants can continue to provide useful hearing for years after hair cell loss, these long-surviving neurons must remain electrically excitable and appropriately connected to their central targets10. Thus, in many types of sensorineural hearing loss, there is a long therapeutic window wherein a treatment to elicit neurite outgrowth could reconnect silenced cochlear ganglion cells with hair cells, and thereby potentially improve speech in noise performance and reduce tinnitus. End quote.

I hope it is like that, because by the time there is some sort of regeneration available, my hearing loss will be years "old".
 
#1,439
Reinier said:
What I do not understand than is why cochlear implants are still able to work, even after decades? (Jeff had hearing loss for a long time and I understand he is detecting high frequencies again).
Also in this article (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4842978/) I read that that the reason that cochlear implants can still work after many years must be because of the long time surviving neurons. In order to make use of a cochlear implant you need it to get the signals from this implant to your brain.
Quote: Given that cochlear implants can continue to provide useful hearing for years after hair cell loss, these long-surviving neurons must remain electrically excitable and appropriately connected to their central targets10. Thus, in many types of sensorineural hearing loss, there is a long therapeutic window wherein a treatment to elicit neurite outgrowth could reconnect silenced cochlear ganglion cells with hair cells, and thereby potentially improve speech in noise performance and reduce tinnitus. End quote.

I hope it is like that, because by the time there is some sort of regeneration available, my hearing loss will be years "old".
Click to expand...
I read interview with some researcher and she said auditory nerve unlike other nervers dont degenerate after not use. She told she had patient succesfully fitted with CI after 60yrs of deafness in that ear.
 

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