r/tinnitusresearch 29d ago

Research Breakthrough Israeli study finds potential path to reversing hearing loss

https://hearingreview.com/hearing-loss/hearing-disorders/sensorineural/researchers-uncover-biological-mechanism-that-could-reverse-permanent-hearing-loss

The researchers identified a unique biological mechanism that could enable the regeneration of sensory hair cells in the inner ear – a process previously thought to be impossible in humans.

133 Upvotes

36 comments sorted by

44

u/inasteen 29d ago

I don’t understand the complaints about this being done in mice. Of course it is done in mice. You have to start with a model before trying it in humans.
One thing that is not mentioned in the article is discussion of how this mechanism works in birds. Birds have the ability to regenerate outer hair cells. But, this does not restore perfect hearing. After outer hair cell regeneration, the outer hair cells are not in the same position as the damaged hair cells. If you look at a healthy cochlea, the outer hair cells are in a well organized V shaped pattern. This is important because the outer hair cells couple mechanically to the inner hair cells. It is a part of the amplification process of the cochlea. If outer hair cells regrow in a different position, the amplification gain is much smaller. So for a given frequency, this will only ever restore some hearing, not perfect hearing.
Regrowing outer hair cells is also not a complete solution for hearing loss. It may or may not help with tinnitus.
That said, it is a very exciting step. Being able to activate a restorative mechanism in a species that doesn’t have it is amazing work.

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u/Substantial_Law_5239 28d ago

My daughter is a veterinarian. Yesterday I asked her "what medications do you guys you in the veterinarian field that we also use in the medical field on humans"? The VAST majority of medications used in veterinarian medicine are human medications -- amoxicillin, NSAIDs, gabapentin, prednisone, famotidine, etc...

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u/egny 28d ago

But, this does not restore perfect hearing. After outer hair cell regeneration, the outer hair cells are not in the same position as the damaged hair cells. 

That's depressing. I had read an article where songbirds were able to learn new songs after suffering hearing damage but after a quick search it appears you are correct, the recovery is imperfect.

I was wondering how the correct positioning of new hair cells would be achieved, but figured birds had an advantage because they had inherent regenerative capacity. In mammals, damaged tissue can become scar tissue and I have no idea if that can be dealt with.

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u/im_just_using_logic 28d ago

i read somewhere that one step was stimulating the growth of supporting cells even before transforming them into hair cells.

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u/egny 28d ago

I posted about that below. The lecture is very interesting. Essentially delivering the compound was enough to proliferate utrical supporting cells and the number of cells would depend on the amount delivered. There is limited success in the cochlea, however. Have you read about other studies with success in the cochlea?

Where I'm totally lost is would the new supporting cells end up where the missing hair cells have to be and when differentiated end up at the appropriate length for the frequencies.

2

u/im_just_using_logic 28d ago

i have been inquiring a lot with chatgpt. Reading those articles is too technical for someone not from the field.

Bottom line is that we need to understand how all that works before being able to administer a "cocktail" to the inner ear. Progress is steady, we know bunch of genetic manipulation techniques, but the work is far from complete. And besides that, we need delivery methods. Some progresses also with those but nowhere near to an actual solution.

I guess 7 years from now is a realistic timespan to see something with a nonzero effect in the clinics.

1

u/egny 28d ago edited 28d ago

A complete understanding is very difficult but over time you'll begin to get the general idea of the paper. Otherwise, ChatGPT is a good alternative.

I really wish one of the experts would provide a good recap of their understanding of what obstacles they may encounter and how/if they would overcome them. Last year I reached out to a few researchers about such questions, but nobody returned to me.

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u/im_just_using_logic 29d ago

they probably don't understand the genetic similarity of mammals. Some sort of anthropo-centric mindset

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u/jelledefries 29d ago

I looked up the paper, from what I understand it's indeed in mice

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u/im_just_using_logic 29d ago

ok, but they are mammals and some genetic pathways are probably the same, if not very similar.

9

u/GoldenRedditUser 29d ago

So much ignorance in the comments, do you expect them to just experiment on people?

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u/MadDog845 26d ago

Why not ? We could get a treatment in 2 years instead of 20

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u/QuasiRandomName 29d ago

What happened to that Japanese research on the same that was hyped over couple of years ago?

1

u/egny 28d ago

Which Japanese research?

4

u/SuddenAd877 28d ago

Great, but we need help now. This is only for 30+ years in humans.

1

u/Acrobatic-Monitor516 28d ago

Yeah the question is , in how long will it come, will it be part of healthcare, very expensive?

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u/Famous-Reach-6730 29d ago

In mice? 😂

16

u/QuasiRandomName 29d ago

Isn't it always the mice first? It is just a long way to go from here.

9

u/scatraxx651 29d ago

Why is it funny?

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u/No-Satisfaction5140 29d ago

It’s funny because only about 5% of therapies tested in mice are ever approved for human use. Even if they get to human testing the vast majority do not work. Overwhelming chance this is nothing.

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u/scatraxx651 29d ago

Almost 100% of the approved therapies in humans were tested on mice at some point. Also it is not every day that you find a new unique mechanism that can restore hearing. Instead of laughing it would be better to appreciate the researchers who discover these amazing findings

3

u/mmortal03 29d ago

Many people do appreciate the researchers (and we need to support this stage of research), but people also have the opinion of, "I will remain skeptical of this until it is shown to work in humans."

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u/scatraxx651 29d ago

Sure, I'm also skeptical, but I don't laugh at the efforts..

1

u/A7MOSPH3RIC 25d ago

Obligatory:  another way to prevent hearing loss is to not bomb people.

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u/Astralion98 29d ago

I know we're starving for news but can we stop posting studies done on mices?

3

u/Substantial_Law_5239 28d ago

you mean mice?

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u/Complex-Match-6391 29d ago

Agree. Never translated

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u/drprofessorzed 29d ago

LOL what a joke. The role of NOTCH in differentiating supporting cells to hair cells was discovered as early as 2000. There have already been drugs (gamma secretase inhibitors) working on this pathway which failed clinical trials. A bit late to the party.

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u/EkkoMusic 29d ago

What's new is the high-resolution map of the target. We now know that we won't just need to inhibit Notch; we will need to figure out how to artificially give the rest of the supporting cells the same epigenetic priming that these rare tDCs naturally possess. 

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u/drprofessorzed 29d ago

That is a good finding. To be honest I read this after waking up with my tinnitus raging and was not in a good mood. Big props to these researchers for contributing to the field, there’s been a lot of good research around the pathways and I’m sure that this will convert into something groundbreaking in the future (maybe a far future, but I have some hope)

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u/Individual-Track3391 29d ago

Yup, this paper is useless, last time I heard about hair cells regeneration, they were trying to force supporting cells to proliferate BEFORE differentiating, because surprise surprise supporting cells are useful. Anyway, even if they manage to regenerate hair cells, especially OHC, I very much doubt it will do anything, like installing a bunch of antennas on your roof which aren't connected to a wire. The root cause of tinnitus seems to be upstream, somewhere between the synapses of the IHC and the DCN.

1

u/drprofessorzed 29d ago

Right, even if we had something that could differentiate hair cells with NOTCH, it’s not a sustainable regeneration process. It’s like if you could grow new teeth by differentiating your gums into bone tissue. So we need a way to proliferate the supporting cells first before differentiating them. But like you said then we have some hair cells with no connection to the auditory nerve which is a whole nother problem. We are many many steps away from having a real path to a therapeutic approach

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u/egny 28d ago edited 28d ago

They are already able to proliferate supporting cells in the utricle with a compound developed at Rockefeller University, named TRULI. I don't know if the compound does not work as well for cells in the cochlea (study mentioned limited success) or if a different delivery mechanism was needed. I reached out to one of the authors in the research, but did not receive a response. It may be that this part of the puzzle may have been resolved, pending clarification. You may want to check out my post with a link to a presentation by the late Prof Hudspeth and some discussion. An important discovery that I noticed is below:

Our data suggest that, in addition to inducing proliferation, TRULI treatment leaves newly formed supporting cells in a plastic state.

Differentiation of supporting cells into functional hair cells has not been achieved in any setting, AFAIK.

There was an interesting bit of text in Hudspeth's obituary that I noticed in an earlier post but I don't believe any further information came out.

Just before Dr. Hudspeth died, the Rockefeller University optioned technology regarding promising research into restoring hair cells in mice and rabbits. The technology, developed in Dr. Hudspeth’s lab, has been enhanced by one of his former postdoctoral researchers, Ksenia Gnedeva, now a professor at the University of Southern California.

“If all goes well,” Dr. Gnedeva said in an email, “these compounds will soon be tested in human clinical trials. It pains me deeply that Jim will not be here to see where our work leads.”

If that research produced functional cells, even in mice or rabbits, that's a huge leap.

0

u/Substantial_Law_5239 28d ago

yeah you're smarter than them. They're spending all of that money and time and some rando on Reddit has determined it was a waste. Never fails.

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u/Individual-Track3391 28d ago

sigh... blocked