Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Nick47]

That's all great and good but you still get told the same thing.

On my onset of tinnitus worsening and after reading his books, I desperately contacted Dr. Baguley who kindly responded and recommended I try to get an appointment at Nottingham.

After waiting 18 months and going to my appointment eagerly, which was in the same building as he worked, I was then told that no one knows anything about pain hyperacusis, that there was nothing they could do for it or my tinnitus and, after an 18 month wait for the appointment, it lasted 5 minutes. I then got a letter saying I was discharged.

Research is great and needed but these breakthroughs and findings need to develop into meaningful treatments, otherwise what's the point.

@ColinUK, yes agree. That must have felt terrible.

 

[AxEars]

First direct access to the human auditory nerve could offer new hope

Nottingham Biomedical Research Centre - today.

Last month OHSU discovered how the inner ear translates vibrations into sound at a molecular level. This month we now have a safe route to the inner ear.

We march closer to a tangible treatment, seemingly with an accelerated step. We have no idea what could be conceived with this information, or how fast. Not months fast, but not decades slow.

The cochlea is more figured out than ever. I hope this garners more attention from medical research that would have otherwise written off this area of science. All the cool kids want to fix this, right?

We live in tangible hope.

 

[CW Dragon]

I agree. I'm not an expert, but I think that many cases of tinnitus and hyperacusis could benefit from treatments to regenerate hearing, however. My problems, for example, coincide with the onset of my hearing loss. If the normal functioning of my cochlear hair cells and auditory nerve could be restored, I believe there would be good chances for me to be cured or at least to experience some relief.

@CW Dragon, thanks a lot for the video link to Charles Liberman's presentation. Super informative and interesting.

You're welcome! He had another one too, much more recent (last month) but it is pretty similar to the older video:

 

[CRGC]

You're welcome! He had another one too, much more recent (last month) but it is pretty similar to the older video

Thanks for this one as well, super informative! He actually goes a bit further into his thoughts about neurotrophins as treatment. His second-to-last conclusion on this slide appears specifically interesting:

If, as Liberman states, rapid administration of neurotrophin is crucial in regenerating synapses after trauma, could this be a reason for OTO-413's failure? It's possible that patients in the trial did not respond to the drug because they were outside of the acute phase during which synapse regeneration is possible. If that's the case, I don't think it bodes well for us with pre-existing damage. The damage might be done and thus harder, or impossible, to reverse once it has settled in and time has passed.

 

[Nick47]

If, as Liberman states, rapid administration of neurotrophin is crucial in regenerating synapses after trauma, could this be a reason for OTO-413's failure? It's possible that patients in the trial did not respond to the drug because they were outside of the acute phase during which synapse regeneration is possible. If that's the case, I don't think it bodes well for us with pre-existing damage. The damage might be done and thus harder, or impossible, to reverse once it has settled in and time has passed.

I'm always hyper vigilant when claims are made for tinnitus, hyperacusis or hearing loss. We always need to look out for those that are preventative or acute treatments and weed them out. I think this is a stunt Hough Ear Institute tried to pull.

However, I think with OTO-313 and FX-322 all participants recruited were past the acute phase.

 

[Jupiterman]

I think with OTO-313 and FX-322 all participants recruited were past the acute phase.

Unless these regeneration medicines CAN deal with post-acute phase cases, there would be little benefit to society.

Prednisone already does a fairly good job at the acute phase.

These pharmaceutical companies are absolutely right to adapt and test their treatments to help those long past the acute phase, which is probably 99.9% of people who have tinnitus.

 

[AfroSnowman]

Prednisone already does a fairly good job at the acute phase.

These pharmaceutical companies are absolutely right to adapt and test their treatments to help those long past the acute phase, which is probably 99.9% of people who have tinnitus.

Prednisone does not do a fairly good job in the acute phase, rather it is the only tool we have at all.

 

[Nick47]

Prednisone does not do a fairly good job in the acute phase, rather it is the only tool we have at all.

Prednisone is only used in the acute phase for SSHL in the UK and that's if the patient tells the doctor they've gone deaf.

 

[AfroSnowman]

Prednisone is only used in the acute phase for SSHL in the UK and that's if the patient tells the doctor they've gone deaf.

There are a lot of people here, me included, that took Prednisone, but we are here so it clearly doesn't work for everyone.

 

[jeff W]

Thanks for this one as well, super informative! He actually goes a bit further into his thoughts about neurotrophins as treatment. His second-to-last conclusion on this slide appears specifically interesting:

View attachment 52048

If, as Liberman states, rapid administration of neurotrophin is crucial in regenerating synapses after trauma, could this be a reason for OTO-413's failure? It's possible that patients in the trial did not respond to the drug because they were outside of the acute phase during which synapse regeneration is possible. If that's the case, I don't think it bodes well for us with pre-existing damage. The damage might be done and thus harder, or impossible, to reverse once it has settled in and time has passed.

 

[Artemis2K]

Thanks for this one as well, super informative! He actually goes a bit further into his thoughts about neurotrophins as treatment. His second-to-last conclusion on this slide appears specifically interesting:

View attachment 52048

If, as Liberman states, rapid administration of neurotrophin is crucial in regenerating synapses after trauma, could this be a reason for OTO-413's failure? It's possible that patients in the trial did not respond to the drug because they were outside of the acute phase during which synapse regeneration is possible. If that's the case, I don't think it bodes well for us with pre-existing damage. The damage might be done and thus harder, or impossible, to reverse once it has settled in and time has passed.

I'm a bit doubtful that we will have much to worry about. I looked up general nerve regeneration recently, and got plenty of results. If nerves outside the cochlea can be treated after a long period of time, then how can the synaptic ribbons be impossible? Maybe not using exclusively NT-3, but surely there's potential for other methods.

Also, how are these companies getting results if it's not possible to regenerate after 24 hours? They can't just kidnap college aged students after a concert and do experiments lol. As long as Frequency Therapeutics and these other companies get the funding, I am sure we will have something, because surely we must be on the right track.

 

[Artemis2K]

Is there any research on gene therapies that grow new stereocilia support cells? If Frequency Therapeutics's treatment works, that might be the only thing that we'd have to worry about besides maintaining them. I'm pretty certain the support cells are finite otherwise.

 

[d'Wooluf]

Is there any research on gene therapies that grow new stereocilia support cells? If Frequency Therapeutics's treatment works, that might be the only thing that we'd have to worry about besides maintaining them. I'm pretty certain the support cells are finite otherwise.

One of Frequency Therapeutics's selling points was that it would supposedly not deplete the support cells. Once a support cell divides, one of the new cells becomes a hair cell, the other remains a support cell. I think that's how things were supposed to work. It's all a bit moot though if the drug doesn't improve our hearing.

 

[Artemis2K]

One of Frequency Therapeutics's selling points was that it would supposedly not deplete the support cells. Once a support cell divides, one of the new cells becomes a hair cell, the other remains a support cell. I think that's how things were supposed to work. It's all a bit moot though if the drug doesn't improve our hearing.

Do you know the source? I hope that's true, and that it can be shown in clinical trials.

 

[d'Wooluf]

Do you know the source? I hope that's true, and that it can be shown in clinical trials.

Sorry, I haven't got a source at hand. I'm sure one of the Frequency Therapeutics fans will. It was discussed ad nauseam in the Frequency Therapeutics topics.

 

[ThomasF]

Do you know the source? I hope that's true, and that it can be shown in clinical trials.

Cell cycle regulation in hair cell development and regeneration in the mouse cochlea

It is shown in the first image in that link. From what I understand, this ties into the FX-322/FX-345 formula focusing on blocking the inhibiting presence in the cochlea that prevents the progenitor cells from splicing into a replacement stem cell, which turns into a new progenitor cell and the other into a hair cell.

 

[tomytl]

An MHH research team has identified the molecular switch for the formation of inner and outer hair cells and thus found an important building block for the treatment of hearing loss:

Researchers identify important molecular switch for hearing development (phys.org)

MHH original report in German language:

Medizinische Hochschule Hannover : Der Schlüssel zur Hörentwicklung (mhh.de)

EDIT:

From what I have learned, this is basic research without any therapeutic application in the near future. But maybe good to know for some other approaches...

 

[Joeseph Stope]

An MHH research team has identified the molecular switch for the formation of inner and outer hair cells and thus found an important building block for the treatment of hearing loss:

Researchers identify important molecular switch for hearing development (phys.org)

MHH original report in German language:

Medizinische Hochschule Hannover : Der Schlüssel zur Hörentwicklung (mhh.de)

EDIT:

From what I have learned, this is basic research without any therapeutic application in the near future. But maybe good to know for some other approaches...

Yes, it's expanding the knowledge base. Then they put the bits together to come up with new questions or theories.

Of course it can work the other way too: They stumble on something that appears to work, then they have to try and figure out why.

And sometimes they can't figure it out. But who cares? if it works, it works.

Praying for the day that this happens with tinnitus & hyperacusis

 

[tomytl]

One more company with a hearing loss product in the pipeline:

Pipeline - Myrtelle, Inc. (myrtellegtx.com)

 

[Artemis2K]

So, if there are dormant progenitor cells that can turn into hair cells, and the division of support cells can activate neighboring stem cells to become hair cells, and all these cells have the capability of replacing each other, then we in fact have everything that's needed to actually achieve hearing regeneration.

The only question remains is, what is the key to initiating the process? Growth factors, stem cells, gene therapy, or a drug that stimulates the right thing? We supposedly wouldn't even need to worry about synapses since apparently new ones attach with the new hair cells.

 

[kyokucyou]

The only question remains is, what is the key to initiating the process? Growth factors, stem cells, gene therapy, or a drug that stimulates the right thing?

I hope it will be something other than gene therapy. I mean, of course I'd be more than happy if a treatment were available at all, but I think gene therapy would be quite expensive. The cost of CRISPR treatments can be in the range of hundreds of thousands of dollars for some diseases.

 

[Artemis2K]

I hope it will be something other than gene therapy. I mean, of course I'd be more than happy if a treatment were available at all, but I think gene therapy would be quite expensive. The cost of CRISPR treatments can be in the range of hundreds of thousands of dollars for some diseases.

It would be quite expensive at first, but hearing loss affects a large population, and the cost would likely significantly decline because of the popularity making it dominate the market.

I'm just grateful that something other than a cochlear implant is actually scientifically plausible.

 

[Nick47]

We need to accept that there will be no natural way to restore hearing in the next 10 years. It's a fact! Follow progress yes, but clinically it's miles away. We know there will be 'options' for tinnitus much sooner.

So follow out of interest, but realise the current state of play and what that means.

Plus, in 10 years, where will hearing technology be? And if implants and prosthetics are really good solutions, the market for natural restoration may still be there but potential yield greatly reduced.

 

[Jupiterman]

We need to accept that there will be no natural way to restore hearing in the next 10 years. It's a fact!

No one can say that.

We can express our opinions though.

 

[LumberCrack29]

Implants and prostethics can never be substitutes for natural hearing. The day natural restoration comes, the market for hearing aids and implants will definitely go down.

 

[Nick47]

No one can say that.

For something to be available in 10 years, it would need to be in 'human' clinical trials NOW. At least in Phase 1, and it would need to work.

 

[Artemis2K]

I'm going to be hoping for around five years. It doesn't always take that long for stuff to hit the market. I'm going to try alternative methods first before then, hopefully they'll be successful.

It took me six years to finally get to a point where I can graduate because of a lot of bad circumstances, and within that time my left ear got progressively worse. Still don't know why, and cannot know until I can afford to, but I want to try to reverse some of it before I will actually need hearing aid. Tinnitus is unpleasant, but not as agonizing as the other issues.

I don't want to enter a factory as a maintenance technician or engineer without belief that my problems can be resolved in the *near* future. I'm not even 30 yet and I already am reaching a point where I will need hearing aids very soon at the rate it's going. I hate it. It makes me depressed. It makes me angry. Music was one of the biggest things to relieve stress for me during years of depression, and although I kept it under 80 decibels because my audiologists said that under that amount wouldn't cause hearing loss, it apparently does for my left ear. I lost 10 more decibels within a year despite being careful. That's weird. My ENTs weren't helpful a few years ago either, telling me I was fine.

We now know hearing regeneration is plausible, and it seems that mammals have the necessary components, but for whatever reason it's not a natural automatic process, so researchers now have to find a way to trigger it. That's a really good development than how it was a few years ago. I want to believe that I can be in my mid 30's when it hits the market. I hate my left ear so much. I need something to keep me sane.

Sorry for the venting.

Anyway, I'm going to keep hoping the key to regeneration is there. Maybe it's something unexpected, simple, and easy to put in the market compared to other things, almost like watering a plant, but with a special serum for the cochlea using something that would stimulate the cells into generating new healthy ones. Hopefully it won't be a matter of cloning cochlear cells for a transplant or gene therapy. I would really hate it if that were the conclusion. I don't want there to be a time window of efficacy either.

 

[Artemis2K]

So, if there are dormant progenitor cells that can turn into hair cells, and the division of support cells can activate neighboring stem cells to become hair cells, and all these cells have the capability of replacing each other, then we in fact have everything that's needed to actually achieve hearing regeneration.

The only question remains is, what is the key to initiating the process? Growth factors, stem cells, gene therapy, or a drug that stimulates the right thing? We supposedly wouldn't even need to worry about synapses since apparently new ones attach with the new hair cells.

I went down the growth factor rabbit hole once again because of Spiral Therapeutics and Otonomy, and my attention was brought back to IGF-1.

If IGF-1 can do the following: Induce proliferation of new hair cells and support cells, as well as repair hair cells and synaptic ribbons, and if new support cells and ribbon synapses can grow with new hair cells according to other research, then why hasn't there been more studies on IGF-1? Why hasn't there been a clinical trial on this? The focus lately seems to be on molecular therapy, BDNF (another growth factor), NT-3 (another growth factor, but no apparent clinical focus on IGF-1. Why?

It's already been approved by the FDA for use in other ways. If there was a human clinical trial for this, how much would that cost, and how long could that take? IGF-1-LR3 is like around $100 per MG for research. I really think that clinical trials should happen for this. It looks so inexpensive for that. It's disappointing that this is being overlooked.

 

[kyokucyou]

Today I found out about a gene therapy regeneration project that has been active since 2019 and will be finished in 2024:

Gene therapy of inherited and acquired hearing loss

In the "Reporting" section it is written that it is expected for clinical trials to be started, but what will come of it remains to be seen.

 

[SmallRonnie]

Today I found out about a gene therapy regeneration project that has been active since 2019 and will be finished in 2024:

Gene therapy of inherited and acquired hearing loss

In the "Reporting" section it is written that it is expected for clinical trials to be started, but what will come of it remains to be seen.

It sounds pretty interesting.

It probably would be at last a decade away from market if it even works.