Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Oh, looks who's back. Looks like today's his monthly shitstorm day. I almost forget about you.

It always amazes me that a random, unknown guy from the Internet claims to know more than a half dozen companies which raised like 100 million dollars in the last few months.

A random guy in the internet can fake many things; deep, specific knowledge on complicated problems isn't one of them. We are a community suffering from a widely misunderstood condition, and there are few specialists here on TT to guide us. Let's not drive away the few ones we have.

But still you sound a bit pessimistic
I would suggest you dig a little further in Fx, as a neuroscientist it would be really interesting...i bet

I think he's just detailing the immense difficulty of regenerating the human cochlea. Our current studies show human hair cell regeneration on controlled tissue samples, not in the actual inner ear. Most of the more promising results are in newborn mice or immediately following noise exposure. And regenerating hair cells is just the first step: there is still the matter of reconnecting them to their synapses so that they can actually transmit sound to the brain. So is it impossible to do then? I'd say it's definitely possible, but not in the near future. Of course, Frequency can have extraordinary success and prove us all wrong. Here's hoping.

So is this guy a pessimist, and rightfully so? Are we screwed then? There's no hope at all? Well, not so fast! Since you're asking @HomeoHebbian, and I have spent an ungodly amount of time reading through his posts (sorry for the creepy stalking, man!), let me present a quote from him:

While I am deeply skeptical about repairing the inner ear of someone with chronic, widespread sensorineural failures, I am GENUINELY OPTIMISTIC that we can eliminate (or at least greatly attenuate) tinnitus. That is an easier problem to solve. Sure, tinnitus could theoretically be solved by a really superb inner ear therapy but there are far easier ways. Since this thread is about inner ear regeneration, I'll just leave it at that.

I have no background on medical science, but I agree with his assessment that tinnitus is a brain disorder. The fact that 1) some people have extensive hearing damage but no T/H and 2) Other factors, such as benzos, can cause T/H without touching a single hair cell or nerve fiber; seems to be an indicator that this is true. Inner ear regeneration is just one of the ways to address T. There are many, possibly easier other ways. This, to me, is greatly encouraging! There's a myriad of possible brain based approaches: non-invasive deep brain stimulation, vagus nerve stimulation. Just recently, a new MRI technique was discovered to produce brain scans with greater resolution. Most of this tools are still incipient: new developments can perfect them and lead to new findings. There's all the reason to be hopeful.
 
This ability to focus on different sounds happens for the most part in the brain and only for a small part in the inner ear (outer hair cells)?
I think I can understand that:)
You lost me buddy! :)

What do you mean by "only for a small part in the inner ear"? How can perception of sound happen in the ear? You may see with your eyes, but you perceive with your mind. The same should be true about the ear. This is something that @HomeoHebbian is right about. Perhaps he can offer an explanation of how this focusing works in healthy brains.

What I didn't like about his statement is that he pointed out a flaw in our approach towards treating tinnitus, but he did not offer an alternative approach. Protection he said? Yes, protecting the ear from chemicals would be useful and a welcome development too. But I don't see that coming from the neuroscience department! Forgive me Homeo, but what have the scientists from your own field of study done lately in protecting the ear against aminoglycosides?

As I said earlier, I am all ears about alternative approaches to treating tinnitus. Besides, it's not like alternative approaches are not being explored. It's just that this thread happens to be about the inner ear.
 
But, as I have stated on other threads, I'm enthusiastic about many other approaches to understand and treat tinnitus. This myopic obsession with inner ear regeneration as near-term treatment for tinnitus has always had me totally baffled. I think y'all are barking up the wrong tree!

I personally have just been following the words of another inner ear researcher, Will Mcclean, co-founder of frequency who has been stating for years that restoring hearing has a great chance of "fixing" tinnitus. I suggest you read up on some of their research, it's interesting stuff. If bats, chickens, and frogs have biological mechanisms to regenerate from hearing damage, why can't human beings utilize something similiar?

As a neuroscientist what other possible remedies for tinnitus are you most hopeful for? deep brain stimulation? vagus nerve therapy? drugs that target the kv potassium channels?
 
But, as I have stated on other threads, I'm enthusiastic about many other approaches to understand and treat tinnitus. This myopic obsession with inner ear regeneration as near-term treatment for tinnitus has always had me totally baffled. I think y'all are barking up the wrong tree!
Not everyone is following this only as a T treatment, I have a lot of HL as well and I am mainly interested in this as a treatment for the latter.

I agree with @addot , @HomeoHebbian has been a pessimist in terms of treatment for a long time but he does offer valuable insights, which should be welcomed bere. Although in this case I dont understand them given the progress Frequency and Audion have made

Nor do I agree with your smart money comment. Yes, a protective treatment might be easier to develop and should yield a good return, but for a regenerative treatment, success could lead to tens of billions of dollars. If 100 million people worldwide suffer from bothersome hearing loss and they all pay 1000 dollars for a treatment, we are speaking about 100 billion dollars.
 
I agree with @addot , @HomeoHebbian has been a pessimist in terms of treatment for a long time but he does offer valuable insights, which should be welcomed bere. Although in this case I dont understand them given the progress Frequency and Audion have made.
A degree in neuroscience does not render one an expert in hearing regeneration. I'm sure researchers at Decibel and Frequency could put up a pretty healthy argument against @HomeoHebbian's pessimism
 
Here's a very timely short summary article from JAMA on hearing restoration: http://jamanetwork.com/journals/jama/fullarticle/2643629 It's essentially a news story rather than a scientific article, and it gets at the same optimism/caution expressed here.

It's a bit odd though in that Karp talks about trials in 18 months, Edge is mentioned as being with Audion though I thought he was no longer associated with them, and it says Audion is talking about trials in 3-5 years when there is trial registry information about something this year.
 
We are a community suffering from a widely misunderstood condition, and there are few specialists here on TT to guide us. Let's not drive away the few ones we have.
I understand what you're saying, and in principle, I agree with you. But on the other hand, let's also have some self-respect.

I think he's just detailing the immense difficulty of regenerating the human cochlea.
First of all, no one is trying to regenerate the entire cochlea. We are trying to regenerate the sensory hair cells inside the cochlea, and possibly the nerves and synapses. One advantage of the cochlea compared to other sensory organs is its bony structure and that it keeps the overall architecture even after a person goes deaf as a result of mechanical (noise) or chemical damage.

Just because the task is difficult doesn't mean we should never try. We would not get very far if no one ever tried to make the impossible possible.

I'd say it's definitely possible, but not in the near future.
How can you predict that? What is it you know that makes you so sure it's not possible in the near future? And how do you define "near future"?

Of course, Frequency can have extraordinary success and prove us all wrong.
Including yourself, yes. But not if you are right about this not being possible in the near future. So how do you want it, is it possible or not possible in the near future? You seem to be undecided about this. Of course, no one really knows for sure, that's what these threads are for really.

I can point out a number of things that are "wrong" in science, in economy, in politics, and other areas of life and society. But merely pointing out the problems does not make for a good, constructive discussion.

While I am deeply skeptical about repairing the inner ear of someone with chronic, widespread sensorineural failures, I am GENUINELY OPTIMISTIC that we can eliminate (or at least greatly attenuate) tinnitus.
Chronic, widespread sensorineural failures? Is there any other kind, other than chronic? This seems to allude to the old mantra that hearing damage can be temporary and transient.

To choose skepticism as a scientific philosophy is like choosing immobility as a means of transport.

That is an easier problem to solve.
As opposed to what? Hearing loss? Tinnitus is easier to solve than hearing loss? Then how come we don't have a solution yet?

Sure, tinnitus could theoretically be solved by a really superb inner ear therapy but there are far easier ways.
What does someone coming from a neuroscience background know about the ear? And these other ways of treating it would come from where? Neuroscience department? Again, how come we still don't have a solution yet, if it's all that easy?

I have no background on medical science, but I agree with his assessment that tinnitus is a brain disorder. The fact that 1) some people have extensive hearing damage but no T/H and 2) Other factors, such as benzos, can cause T/H without touching a single hair cell or nerve fiber; seems to be an indicator that this is true.
If it's a brain disorder, what triggers it? If not hearing loss?

How do you ensure that benzos test subjects have not had their hair cells and nerve fibers "touched"? There is no imaging technology available to asses the integrity of hair cells and nerve fibers in live animals. There are ABR and OAE tests. But have these been used in the test subjects? What study are you referring to?

There are many, possibly easier other ways. This, to me, is greatly encouraging!
Yes, possibly easier ways. But is it really easier than restoring the sensory cells of the ear? What evidence is there that treating the brain is easier than treating the ear? The brain is least understood of all the organs.

Yes, it is encouraging. But no one said that other approaches should not be explored. No one really knows where the answer lies. So we need to be honing in on this from different angles. That is not to say that sensory hair cell regeneration should be put aside, and have neuroscientists take the lead on this. Of course, if I were a neuroscientist I would like that very much.

There's a myriad of possible brain based approaches: non-invasive deep brain stimulation, vagus nerve stimulation. Just recently, a new MRI technique was discovered to produce brain scans with greater resolution. Most of this tools are still incipient: new developments can perfect them and lead to new findings. There's all the reason to be hopeful.
Yes, those are all great news and all the more reason to be not just hopeful but optimistic.

Yes, there is that new 7 Tesla MRI scanner, a new promising toy for neuroscientists. On top of that, you have a number of technologies and techniques that they can play around with, including MRI, MEG, PET and CT. If you follow a scientific publication, you can constantly read about new advancements in brain imaging. There is not much going for inner ear imaging.

With all these brain imaging techniques, and with a brain-focused approach to treating tinnitus, you would think we have a cure for it since 10 years back. But the reality is, we are still sitting in the waiting room.

I will just say this! Let the ear scientists follow their hypothesis and brain scientists follow their hypothesis. They should be working together for a cure, rather than competing against each other, and debating whose approach is right and whose approach is wrong.

Perhaps what we need is another thread titled "Brain Cell Regeneration — Maybe We Can Know More". A place where those that are in this camp can feel more welcome. They are welcome here too of course, but the focus of this thread is on inner hair cell regeneration. We should try to keep it on topic.
 
From this:
Here's a very timely short summary article from JAMA on hearing restoration: http://jamanetwork.com/journals/jama/fullarticle/2643629 It's essentially a news story rather than a scientific article, and it gets at the same optimism/caution expressed here.

I quote:
Members of the team [Frequency] report that they have further tweaked the cocktails since publication and, using the middle-ear method of instilling the drugs, observed greater hearing improvement in mice. "We are continually refining our therapeutic combination and have seen promising results," said Will McLean, PhD, formerly of the Harvard-Massachusetts Institute of Technology (MIT), who was a lead author on the most recent publication.
McLean, however, who is now working for Frequency Therapeutics, was undeterred. He said many of the hearing-related neurons remain viable "for years" after hair cells die, adding that when new hair cells are generated, they release molecules known as neutrophins that signal dormant neurons to form new synapses facilitating reconnection with the auditory nerve.

"The job is done for you," noted Karp.

To me, it's as simple as that Frequency wouldn't move to clinical trials (and raised that bunch of money) if there were still so many unanswered, uncharted questions about regain hearing after regenerate hair cells. It looks like Frequency's people did their jobs and know how the brain and hearing work and they are now so far ahead everybody else.

Call me an optimist.
 
I'm sure researchers at Decibel and Frequency could put up a pretty healthy argument against @HomeoHebbian's pessimism
What we really need is for these good people to work together, rather than against each other or alongside each other. Interdisciplinary approach is what we need for tinnitus. Also, as @Rubenslash has noted, and rightfully so, not everyone is interested in this for tinnitus alone. There are people who have hearing loss without tinnitus, or people with tinnitus and hearing loss. They would all be interested in treatments that restore hearing.
 
How do you ensure that benzos test subjects have not had their hair cells and nerve fibers "touched"? There is no imaging technology available to asses the integrity of hair cells and nerve fibers in live animals. There are ABR and OAE tests. But have these been used in the test subjects? What study are you referring to?

You are right, I shouldn't have said no hair cells or nerve fibers were touched. What I intended to say is, in the specific case of benzos, their mechanism on T could be entirely due to brain based phenomena. I also didn't mean the goal is to restore the entire cochlea, but the hair cells/nerve fibers/synapses. Sorry I couldn't make myself clearer. It was never my intention to start a big debate, or to suggest any competition between ear based and brain based approaches.
 
You are an optimist! :)
I don't think it's optimism, but logic. The company has raised big money last few months and won't risk it in hyped vaporware. Besides, if you were a CEO, shareholder, worker, etc. of a company, what would you say about your rivals, especially when they're outperforming you? Hearing loss market is huuuuge and there's a LOT of money at stake. First mover takes it all.
 
First mover takes it all.

I think you mean "winner takes it all" (you can move first but not win the race).
At any rate, I don't think this is the case here, as I don't expect something to work on everyone consistently. No treatment has 100% success rate for everyone. Situations are complex, and having an ecosystem with a variety of treatments to be able to target a set of etiologies is what I would expect is going to happen.

There's variety of NSAIDs out there. Acetaminophen works well for some, not so well for others. Same for ibuprofen, naproxen, etc. You need multiple tools in the toolbox.
 
No harm is done @addot. At least we have some discussion going now. I was not addressing you alone.

What I intended to say is, in the specific case of benzos, their mechanism on T could be entirely due to brain based phenomena.
It could be, yes. That should be investigated, of course.

You are right, I shouldn't have said no hair cells or nerve fibers were touched.
I also didn't mean the goal is to restore the entire cochlea, but the hair cells/nerve fibers/synapses.
Of course, I could read that between the lines. But thank you for clarifying! If we are going to be questioning everything we say and do, then we should at least state clearly what we mean.

It was never my intention to start a big debate, or to suggest any competition between ear based and brain based approaches.
Don't worry about that, the debate started long before that. Also, you did not suggest that, I did. Or at least that was my interpretation of what Homeo was saying. You know, "barking up the wrong tree" remark.

We are all good, let's just see if we can keep the discussion civilized and to the point.
 
I think you mean "winner takes it all" (you can move first but not win the race).
At any rate, I don't think this is the case here, as I don't expect something to work on everyone consistently. No treatment has 100% success rate for everyone. Situations are complex, and having an ecosystem with a variety of treatments to be able to target a set of etiologies is what I would expect is going to happen.

There's variety of NSAIDs out there. Acetaminophen works well for some, not so well for others. Same for ibuprofen, naproxen, etc. You need multiple tools in the toolbox.
Nope, winner takes all is something else. First mover takes all the market since there's just one good offered to meet the whole demand. When competition enters the market, first mover takes it all if the new goods aren't way better or cheaper than the first one.

I didn't implied that Frequency's stuff will work, though, just pointing at the logic behind their moves.
 
Hogwash. @HomeoHebbian and @addot say it ain't so. Somebody write the editor's and alert the investors.
There's no need to be snide. All I did was express my view that brain based therapies might be more fruitful for T and H relief. I didn't say all inner ear research is bound to fail. I'm no researcher, I'm just a guy behind a computer, I did not claim to be right. This is just my takeaway from reading into the research. I may very have gotten it all wrong (which would be great for my T/H wrecked ears!) Should I be ridiculed for having a different point of view than you?
 
First mover takes all the market since there's just one good offered to meet the whole demand. When competition enters the market, first mover takes it all if the new goods aren't way better or cheaper than the first one.

That's called a first mover advantage. It isn't likely that the offering is going to match the demand completely. Like I said, there are many reasons why supply/demand aren't fully matched: the product may not be suitable for the consumer (allergies, problems with the delivery), may not fit the price range for the consumer, may not be available to the consumer (production limits, jurisdiction, local laws), etc.
Being the first one is undeniably a great advantage, but it's very far from winning all.
 
There's no need to be snide. All I did was express my view that brain based therapies might be more fruitful for T and H relief. I didn't say all inner ear research is bound to fail. I'm no researcher, I'm just a guy behind a computer, I did not claim to be right. This is just my takeaway from reading into the research. I may very have gotten it all wrong (which would be great for my T/H wrecked ears!) Should I be ridiculed for having a different point of view than you?
I'm sorry. Please forgive me. I just don't like to see people get swayed by people who hold higher degrees. A degree does not make one an expert in everything. Even academics in the same narrow fields argue amongst themselves.
 
Well look if cellular repair of the ear doesn't do it, there is always neuroscience :) great work being done on neurodegenerative disease with treatments for Alzheimer expected well within the next 500 years, I am expecting big things from the Human Brain Project too, I mean who knows what the limits of the human brain are, this remarkable, incredible, fantastic & amazing organ with seemingly limitless potential. Can we unlock this potential and cure things like tinnitus and blindness. #hopeful :)
 
Well look if cellular repair of the ear doesn't do it, there is always neuroscience :) great work being done on neurodegenerative disease with treatments for Alzheimer expected well within the next 500 years,

I've been waiting for your input on this most recent discussion @jeff W.
You haven't disappointed. Fabulous!
 
How can perception of sound happen in the ear?
Not perception. I understand the ear is like a pick-up device. The brain interprets.
I was wondering if the conscious brain is able to "control" the outer hair cells to a certain extend.
I know that for the eye we are not consciously able to control our iris. That is al automated (-;

I wonder if we concentrate on certain regions in sound (as an example higher frequencies in music) we can make this part of the cochlea more sensitive "using" the outer hair cells.
Or is it only the brain that is responsible for this "tuning in".

I agree that both brain and inner ear research is needed for this. I don't have a clue which field is less complex.
They both sound very, very complex to me.
In an ideal world it would be logical to fix the cause of the problem. For me (and many people) that would be damaged inner ears.
Although I have read that there is a possibility with NIHL the brain is also effected.
 

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