Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[JohnAdams]

I asked this question before if compensating for existing hair cells with damaged synapses with new hair cells will make up and the answer is "we don't know" also other aspects of the audiotory nerve are damaged too.

I fret hair cell regeneration will fail trials once they realize synapse and audiotory nerve fiber damage also need to be repaired. then again I am not anyone qualified I am only making a loose hypothesis.

That's why it works in mice??

"Excessive noise permanently damages hair cells that conduct sound to the brain and are found in an inner-ear structure called the cochlea. A team led by Albert Edge at Harvard Medical School in Boston, Massachusetts, has identified a molecule that can convert other cochlear cells into hair cells. The compound, named LY411575, blocks a biochemical pathway called Notch, which normally prevents supporting cells in the cochlea from developing into hair cells. When applied to the ears of mice deafened by loud sounds, the molecule triggered the generation of new hair cells. By three months after this treatment, the rodents' hearing had been partly restored.

LY411575 would probably need to be delivered locally to the ear in humans to avoid side effects, the authors say."

https://www.nature.com/articles/493274d
I guess that's just a conspiracy theory.

 

[Coleoptere]

Audion has trials with LY411575 but I did not see updates recently

 

[JohnAdams]

Maybe we are vastly over estimating how effective this technology is. Like we're in the 1950's thinking there will be cities on mars by the 1980's.

 

[JohnAdams]

 

[PDodge]

Maybe we are vastly over estimating how effective this technology is. Like we're in the 1950's thinking there will be cities on mars by the 1980's.

I hope not! Seems to be a lot of evidence pointing towards it working

 

[JohnAdams]

I hope not! Seems to be a lot of evidence pointing towards it working

show me. please.

 

[spedgas]

Interesting video. It's dated 2013. I realize mice and humans are both mammals, but jumping from mice to humans feels like a huge step to overcome. Maybe that's what they've been working on for the last five years. I want this to work as much as anyone, but this is the therapy I'm having the hardest time getting excited about.

 

[IvanRus]

@JohnAdams

You are right in your doubts about the current use of stem cells "for the treatment of tinnitus," or, especially, for the restoration of hearing.

Of course, today's proposal for systemic stem cells for hearing is a complete absurdity and fraud.

Honestly, it's crazy for me how adults from developed countries can believe such nonsense and give tens of thousands of dollars to it.

Today there are no stem cells in the world that could help with hearing or tinnitus.

It is sad that people are wasting hard-earned money on placebo and scammers, instead of helping real scientists who are working on real treatment. Every 100 dollars bring closer the day when a real treatment appears on the market.

 

[Pero1234]

Hi, is the REGAIN Audion trial still going ahead. I haven't read anything about it lately.

Sorry if this has been answered elsewhere.
Thank you.

Last news article on their website is from 2017

 

[Contrast]

That's why it works in mice??

"Excessive noise permanently damages hair cells that conduct sound to the brain and are found in an inner-ear structure called the cochlea. A team led by Albert Edge at Harvard Medical School in Boston, Massachusetts, has identified a molecule that can convert other cochlear cells into hair cells. The compound, named LY411575, blocks a biochemical pathway called Notch, which normally prevents supporting cells in the cochlea from developing into hair cells. When applied to the ears of mice deafened by loud sounds, the molecule triggered the generation of new hair cells. By three months after this treatment, the rodents' hearing had been partly restored.

LY411575 would probably need to be delivered locally to the ear in humans to avoid side effects, the authors say."

https://www.nature.com/articles/493274d
I guess that's just a conspiracy theory.

LY411575 would probably need to be delivered locally to the ear in humans to avoid side effects, the authors say."

 

[Contrast]

Interesting video. It's dated 2013. I realize mice and humans are both mammals, but jumping from mice to humans feels like a huge step to overcome. Maybe that's what they've been working on for the last five years. I want this to work as much as anyone, but this is the therapy I'm having the hardest time getting excited about.

that's why they should test it on non human primates.

 

[JohnAdams]

LY411575 would probably need to be delivered locally to the ear in humans to avoid side effects, the authors say."

My point is that it probably regenerates the needed synapses.

 

[JohnAdams]

that's why they should test it on non human primates.

or...perhaps a part of the scientific community considers that it will not work. But we need to keep hopes high

But, it might actually work. Therefore all pessimism should be cast aside by the researchers and they should base their opinions on empirical data.

 

[Spiral]

show me. please.

Unfortunately, all we have are the preliminary studies of the drug in mice as well as a cochlea on a petri dish

We just have to wait for Frequency to do their magic and release the complete results for Phase 2.

 

[Margus]

I know such studies are like at least 10 years away from human trials, but still good to know about new discoveries:
Study points to possible new therapy for hearing loss
https://www.sciencedaily.com/releases/2018/10/181015132953.htm

 

[JohnAdams]

I know such studies are like at least 10 years away from human trials, but still good to know about new discoveries:
Study points to possible new therapy for hearing loss
https://www.sciencedaily.com/releases/2018/10/181015132953.htm

"It's funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration," said Jingyuan Zhang, Ph.D., with the University of Rochester Department of Biology and a co-author of the study. "We're the only vertebrates that can't do it."

Oh yeah really funny. I'm laughing my ass off. Get this shit into my cochlea now.

 

[Rudy R]

I can only wonder how much any treatment could cost though. This stuff is expensive to develop.

 

[JohnAdams]

I can only wonder how much any treatment could cost though. This stuff is expensive to develop.

fuck that, let taxes pay for it. Congress pays for crazy bullshit all the time.

 

[Rudy R]

fuck that, let taxes pay for it. Congress pays for crazy bullshit all the time.

I live in Mexico, fam. I wish advancements in medicine were this country's thing.

 

[PolishSoldier87]

"In summary, mammalian inner ears contain several HC subtypes that vary in their morphology and organization within and between different sensory epithelia and species. Current attempts to generate new HCs have thus far yielded only vHC types; however, these vHCs will not function in the OC due to presence of kinocilia and stereocilia organization and will thus not be able to restore their lost hearing at the needed sensitivity. Understanding the differential molecular evolution and development leading to HC heterogeneity may lend insights into the unique processes that result in the formation of the correct HC subtype in the right position with the proper polarity essential for function, including connection of HCs to their central targets by afferents."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092489/

Look at those images.
I do not know whether it will be possible to regenerate everything with needed accuracy.

 

[Jim51042]

like at least 10 years

Are you sure on that timeframe? Any reason they couldn't start phase 1 in say 5-7 years??

 

[JohnAdams]

I live in Mexico, fam. I wish advancements in medicine were this country's thing.

Dude mexibro, go find an ENT down there and tell him about this.

https://www.sciencedaily.com/releases/2018/10/181015132953.htm

Mexico has looser laws in this area. If you find an ENT that will inject us with this stuff we can all come down and dance around to eric rincon in long pointy boots. And them come back and deny Jasterboff his beer.

 

[PDodge]

show me. please.

What about all those studies

Dude mexibro, go find an ENT down there and tell him about this.

https://www.sciencedaily.com/releases/2018/10/181015132953.htm

Mexico has looser laws in this area. If you find an ENT that will inject us with this stuff we can all come down and dance around to eric rincon in long pointy boots. And them come back and deny Jasterboff his beer.

Go do this. I will fly down for some black market therapy

 

[1000]

Dude mexibro, go find an ENT down there and tell him about this.

https://www.sciencedaily.com/releases/2018/10/181015132953.htm


Mexico has looser laws in this area. If you find an ENT that will inject us with this stuff we can all come down and dance around to eric rincon in long pointy boots. And them come back and deny Jasterboff his beer.

https://yelp.com/search?cflt=earnosethroat&find_loc=Tijuana,+Baja+California

@Rudy R Porfavor Please

 

[Contrast]

Frequency Therapeutics stated that their drug will only be effective on mild/moderate hearing loss
(William Mclean on reddit) based on how they work with supporting cells.

Otonomy seems to view gene therapies as effective on severe hearing loss

----------------------------------------------------------------------------------------
Novartis's stage 3 trial also only wants severe hearing loss patients

@attheedgeofscience made a comment about gene therapies for hearing loss regeneration
saying they would only be effective for severe hearing loss as regenerated hair cells will not register noise until 25db.


My question is Do gene therapies only work on severe hearing loss?

Where as progenitor cell activation therapies are only expected to work on mild hearing loss?

 

[AmericanJosh]

Be cautious eith sterm calls. There are many more promises than proven treatments. The FDA advises caution , https://www.fda.gov/forconsumers/consumerupdates/ucm286155.htm

The rise of unproven stem cell therapies turned this obscure scientist into an industry watchdog, Science Magazine.

https://www.google.com/url?sa=t&sou...WMAN6BAgHEAE&usg=AOvVaw0Qrb44gkBALhDub1khlPX_

 

[lymebite]

Be cautious eith sterm calls.

The term "stem cells" has become such a loose phrase these days, it means everything from umbilical cord products from a frozen vial (such as Liveyon in the United States) to fresh umbilical cord stem cells (such as Stem Cells 21 in Thailand and the Stem Cell Institute in Pamama) to autologous stromal vascular fraction stem cells (such as with the Cell Surgical Network in the United States) and a whole lot more variations. Saying "stem cells" has become almost as general a term as saying "medicine."

That all said, my hope is with the stem cell breakthroughs coming out of places like the Harvard Stem Cell Institute. Their discoveries have spawned organizations using stem cells for hearing regeneration such as Akouos, Audion Therapeutics, Decibel Therapeutics, and Frequency Therapeutics. A full list of companies for all conditions, not just hearing disorders, appears at the link.

https://hsci.harvard.edu/company-startups-0

 

[Manny]

(William Mclean on reddit) based on how they work with supporting cells.

I think it's likely that there's a considerable grey area, and variation between individual patients. (Note that the level immediately following moderate is severe, not profound.)

 

[Contrast]

I think it's likely that there's a considerable grey area, and variation between individual patients. (Note that the level immediately following moderate is severe, not profound.)

It won't help severe hearing loss.

Quit pretending it will.

 

[streeter1985]

Don't know if someone already posted that link (published 2012).

Good explanation about severe/profound hearing loss in the cochlea concerning epithelium condition.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637947/

On one hand it says that severe to profound hearing loss patients are potential candidates for hair cell regeneration on the other hand things like Atoh1 didnt work in such damaged areas but I dont know much about Atoh1 so I cant comment on this anyway....