Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Paulmanlike]

Since this discussion doesn't have to do with research on regeneration of hair cells - or other aspects of the inner ear - and since it seems to be important to you, perhaps you should create a separate thread for research on this topic. I saw you have created on in support already.

There was discussion amongst members about whether regenerating hair cells and reversing hearing loss would actually reduce tinnitus. Here I directed people to a paper where a tinnitus expert said " Restoration of audiotory input should reduce tinnitus".

What are your views @Aaron123 ?

 

[fabien]

anyway if you have tinnitus, you are likely to have hearing loss later in life, and it's as bad as tinnitus if not worse.

When you have hearing loss, you have a permanent pressure in the ear, it's an illusion, it's just the difference of hearing. Its as bad as tinnitus.

I have lost about 30 decibels in the right ear last year, due to music exposure again. Luckily i recovered in one week.

The hearing loss, the pressure that change everytime you turn the head, is worse than tinnitus. Plus the fear of losing the other ear. It was definitely worse.

 

[Aaron123]

Restoration of audiotory input should reduce tinnitus".

It's great that you included a reference. However, the this thread is about research on the regeneration of hair cells though it sometimes expands to other inner ear topics that don't really belong elsewhere or aren't "large" enough to merit their own topic. A conversation about the relationship between hair cell restoration and tinnitus deserves its own topic both so that it doesn't get lost here and so that it doesn't derail this thread.

What are your views @Aaron123 ?

My views are that this discussion is off-topic. I will respond in the thread on opinions about hearing loss and tinnitus.

 

[EatMoTacos]

http://www.nature.com/nbt/journal/v35/n6/full/nbt.3840.html

Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells

The derivation of human inner ear tissue from pluripotent stem cells would enable in vitroscreening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR–Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.

 

[Aaron123]

Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells

The derivation of human inner ear tissue from pluripotent stem cells would enable in vitroscreening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR–Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.

This was posted when it first came out: https://www.tinnitustalk.com/thread...ybe-we-can-know-more.3131/page-83#post-247300

 

[EatMoTacos]

This was posted when it first came out: https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/page-83#post-247300

OK!

 

[tomytl]

Some news from Otologic
http://newsok.com/article/5560970

 

[Jim51042]

The trial alluded to above was a Phase I trial that was completed in 2015 (https://clinicaltrials.gov/ct2/show/NCT02259595), but there hasn't been an announcement of a Phase II study in the last 2 1/2 years or any publications on the safety of the drug (NAC + HPN-07). They are, however, continuing to do animal studies: https://www.ncbi.nlm.nih.gov/pubmed/28438658

This is all really weird. Why would they continue spending time and money if they weren't going move to stage 2? Also ok if this is just a ploy for money wouldn't it be easily verifiable. Another company could independently test this pill because the compound are somewhat well known. If this is a "lie" wouldn't that be a stupid and legally risky strategy. Aaron might be right but it's it would be a weird not well thought out ploy.

Im also curious to know how they identified the synaptic regrow. Did they test and then dissect mice primates what?

 

[Flamingo1]

Some news from Otologic
http://newsok.com/article/5560970

Too good to be true

 

[IAmCalifornia]

Too good to be true

Or finally a breakthrough

 

[jdjd09]

Some news from Otologic
http://newsok.com/article/5560970

Wait, I'm confused now. So Hough Ear is now saying that the "bomb blast" pill, that was supposed to prevent hearing loss after noise, can now possibly regenerate long term hearing loss as well (long after it occurred)? When will they allow this pill to come out for hearing loss restoration probably and do they feel confident it works for that?

 

[Paulmanlike]

Wait, I'm confused now. So Hough Ear is now saying that the "bomb blast" pill, that was supposed to prevent hearing loss after noise, can now possibly regenerate long term hearing loss as well (long after it occurred)? When will they allow this pill to come out for hearing loss restoration probably and do they feel confident it works for that?

It's still unclear from the article and whether it could repair long lasting damage. It appears to me that it may only benefit given shortly after trauma and it could help repair nerves giving some improvement.

 

[jdjd09]

Has anyone heard otherwise? Someone on here must know if they discovered if they think the pill does that too.

 

[jeff W]

No, but I have heard that unilateral loss is now being considered for a phase 2 of cgf166. I remember when Genvec paused their trial and the stock plummeted, they still kept their facebook and social media posts open and recovered, it seems that these storms are great for testing the "quality" of those involved or maybe its just that it reveals the conviction of the trial organizers.

 

[Paulmanlike]

No, but I have heard that unilateral loss is now being considered for a phase 2 of cgf166. I remember when Genvec paused their trial and the stock plummeted, they still kept their facebook and social media posts open and recovered, it seems that these storms are great for testing the "quality" of those involved or maybe its just that it reveals the conviction of the trial organizers.

It's worked for mice and monkeys.

 

[Paulmanlike]

No, but I have heard that unilateral loss is now being considered for a phase 2 of cgf166. I remember when Genvec paused their trial and the stock plummeted, they still kept their facebook and social media posts open and recovered, it seems that these storms are great for testing the "quality" of those involved or maybe its just that it reveals the conviction of the trial organizers.

Was this because of their difficulty recruiting patients?

 

[acufenero]

No, but I have heard that unilateral loss is now being considered for a phase 2 of cgf166.

Is this good news or bad news?

 

[rsmcfar]

I have always been curious why those of us with single sided deafness are not ideal candidates for clinical trials, and yet most of the clinical trials require bilateral hearing loss. My recollection is the cgf-166 trial was having trouble recruiting because their ideal candidate had most likely already had a choclear implant.

 

[RB2014]

I have always been curious why those of us with single sided deafness are not ideal candidates for clinical trials, and yet most of the clinical trials require bilateral hearing loss. My recollection is the cgf-166 trial was having trouble recruiting because their ideal candidate had most likely already had a choclear implant.

It might be because something caused that single sided deafness and it could affect the results. From what I have seen they are looking for patients with noise induced hearing loss that has happened naturally over time.

Has anyone heard otherwise? Someone on here must know if they discovered if they think the pill does that too.

No one on here is going to know. Their claims and research up to this point have been suspect so I wouldn't put too much stock in what they are claiming. They could just be looking for more research dollars.

They talk about regrowing nerve endings, but isn't it the hair cells that die off that we need back? Again, it just leaves too much to speculation at this point to take it seriously.

 

[jeff W]

It's worked for mice and monkeys.

I am not talking about primates or rodents. http://www.hearinglossjournal.com/cgf166-latest-news/

 

[Jim51042]

They talk about regrowing nerve endings, but isn't it the hair cells that die off that we need back?

Nope. I can't state this more clearly, for people with minor hearing loss and tinnitus synaptic loss is what matters. As investigatory science progresses this will become accepted fact. As a forum we need to be better and understand the vital role synapses play in the tinnitus disorder!!

 

[jer]

So this whole regrowing the haircells that loads of companies are working on, would that even do anything for us? @Jim51042

 

[Reinier]

So this whole regrowing the haircells that loads of companies are working on, would that even do anything for us?

For me (and many others) it would. I have hearing loss (shows on audiogram). So less detected sound is reaching my brain and is therefore not "masking" my tinnitus. When sound from outside world is reaching brain at higher levels, my tinnitus should/could be less intrusive (hearing aids principle sometimes works the same). That is how I understand it.
I read posts where people have this experience.

 

[threefirefour]

So this whole regrowing the haircells that loads of companies are working on, would that even do anything for us? @Jim51042

Short answer: probably not. It's obvious people still think this is the answer to the tinnitus question. So first we have to restore hearing so people can realize that this won't fix the problem, THEN get to the good stuff, fixing the brain. That will fix the problem.

 

[Jim51042]

So this whole regrowing the haircells that loads of companies are working on, would that even do anything for us? @Jim51042

Yes regenerating hair cells prompts the body to sync up new nerve connections to those new hair cells ergo you get more nerve connections. Plus the whole you may be able to hear even the faintest sounds (aka -10dBa in the sound proof room) is icing on the cake.

 

[jeff W]

Short answer: probably not. It's obvious people still think this is the answer to the tinnitus question. So first we have to restore hearing so people can realize that this won't fix the problem, THEN get to the good stuff, fixing the brain. That will fix the problem.

I have opened a thread on this. You are more than welcome to post your thoughts on neuroscience and brain theory there.

 

[jer]

Thank you guys for all the answers.

 

[Berik]

Yes regenerating hair cells prompts the body to sync up new nerve connections to those new hair cells ergo you get more nerve connections. Plus the whole you may be able to hear even the faintest sounds (aka -10dBa in the sound proof room) is icing on the cake.

Is there any indication how much hearing could be restored?

 

[Jim51042]

Is there any indication how much hearing could be restored?

That's the billion dollar question.

 

[Paulmanlike]

Will if fix hidden hearing loss? (Those with normal audiograms)