Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[attheedgeofscience]

You are entitled, but I don´t see how Otonomy´s approach will differ from FTX regarding how "chronic tinnitus is likely to extend well beyond the cochlea itself."

This is overall true. But, what I like about Otonomy is that they have demonstrated restoration of both the hair cells and the ribbon synapses (in an animal model). And so, I wasn't necessarily commenting on the "utility value" of either OTO or FT with regards to tinnitus, but more in terms of their likely progression to clinical trials (in general).

I didn't come here to bring bad news - I came here to bring an alternative view (that seemed not to have been touched upon). And that view included suggesting that Otonomy is in a better position than Frequency Therapeutics. No more, no less. I didn't steal anything from anyone. Not your hope, not anything. If I did steal anything, it might have been a bit of "false hope".

On a more general note, if each and every person who visits TinnitusTalk would donate just one dollar per annum, this board would have in excess of one million dollars to work with. For a site with basically no overhead, that is a pretty decent sum of money and could lead to some serious advocacy efforts. Similarly, if each of you, for every 10 updates you post in public, would put aside one hour of advocacy efforts, this board would have 25,000 hours of free volunteering efforts. That's about 25,000 hours / (40 x 52 hours) = 25,000 / 2,080 = 12 FTEs for a full year.

Instead, I see the TinnitusTalk community alienating itself from (itself) and everyone else. Here is a prime example of that:

www.tinnitustalk.com/threads/research-to-examine-the-support-for-people-with-hearing-loss-who-experience-tinnitus.9964

The BTA has not been seen since. I wonder why...

 

[tomytl]

This is overall true. But, what I like about Otonomy is that they have demonstrated restoration of both the hair cells and the ribbon synapses (in an animal model). And so, I wasn't necessarily commenting on the "utility value" of either OTO or FT with regards to tinnitus, but more in terms of their likely progression to clinical trials (in general).

I didn't come here to bring bad news - I came here to bring an alternative view (that seemed not to have been touched upon). And that view included suggesting that Otonomy is in a better position than Frequency Therapeutics. No more, no less. I didn't steal anything from anyone. Not your hope, not anything. If I did steal anything, it might have been a bit of "false hope".

On a more general note, if each and every person who visits TinnitusTalk would donate just one dollar per annum, this board would have in excess of one million dollars to work with. For a site with basically no overhead, that is a pretty decent sum of money and could lead to some serious advocacy efforts. Similarly, if each of you, for every 10 updates you post in public, would put aside one hour of advocacy efforts, this board would have 25,000 hours of free volunteering efforts. That's about 25,000 hours / (40 x 52 hours) = 25,000 / 2,080 = 12 FTEs for a full year.

Instead, I see the TinnitusTalk community alienating itself from (itself) and everyone else. Here is a prime example of that:

www.tinnitustalk.com/threads/research-to-examine-the-support-for-people-with-hearing-loss-who-experience-tinnitus.9964

The BTA has not been seen since. I wonder why...

Is there some reading about the Otonomy Regenerative Approach?

 

[Rubenslash]

Is there some reading about the Otonomy Regenerative Approach?

On their website, they mention it as a pre-clinical product currently called OTO-4xx (http://www.otonomy.com/pipeline/oto-4xx/). In addition, following two slides were included with regard to this product in the corporate presentation of June:

I have to say it looks promising as well. I guess Frequency gets more attention here because they do seem to reach the community better (press releases, research papers, reddit,..) and already announced that a clinical trial will start in 2018. Otonomy has a very interesting pipeline and is listed on the NASDAQ:

 

[Nate Croteau]

 

[DoNotGoGentle]

David in this video talks about the progenitor cells being in he right place. That should put to rest people who wondering if the cells end up in the right place!

 

[jeff W]

My inbox went "ping" and I got excited, then opened up my alerts to a post on "Otonomy". 2017 and they are still peddling steroids on us They pop up from time to time on social media with stuff like this

Like Richie Rich trying to buy friends!

or this one
#thingspharmado4money

But this, this is my favourite stooge piece, they got a company (that trades on the stock exchange, $INCR so not a real academic institution) to do a bullshit award and then give it to them! It's hysterical!!
http://www.edp24.co.uk/news/health/...th-award-for-disease-clinical-trial-1-5061451

I'll hang on for the cellular repair trials thanks!


By the way, I have invested in GNVC now intrexon, whilst I wish the company does well, I really don't give a shit who gets there first, I just want results, who gets them first is not important to me.

 

[jeff W]

Thanks for posting, I have not seen this before.

 

[Flamingo1]

I realize my opinion may not reflect the populist view, but, we are all different, right...? And, I would - for a number of reasons - still consider Otonomy to be the safer bet.

I have not heard of Otonomy before. It's nice to know there's another player in the field. Thanks for sharing!

 

[FIGHT]

This will gonna be a long battle for us. I'm praying that these biopharma will deliver the drugs we need sooner and affordable. Drugs are nonsense if we can not afford them.

 

[tomytl]

This will gonna be a long battle for us. I'm praying that these biopharma will deliver the drugs we need sooner and affordable. Drugs are nonsense if we can not afford them.

Yes, we can only hope.
But at least the Regain Trial is also driven with public money (from the EU), so there are not alone the tentacles of pharma companies involves.
At least, pharma conpanies are also interested to earn money and bring out the blockbusters to satisfy their shareholders.
But yes, it won't be a short course anyway....

 

[Champ]

Hell yeah Boston I seriously hope they are super successful with this.

 

[tomytl]

Because of big excitement I make a double post....

Hi,
a new INC to cure hearing loss with top scientists went online these days.
http://rescuehearing.com/
It's exciting! Read about the Founder and the researchers.
Greets Tom

 

[Reinier]

In 2012 HHF suggested it is not yet certain that supporting cells remain after NIHL. (38:44)
They where going to investigate this in the following 5 years.
It is 5 years later now. I wonder if the researchers know now what they set out to investigate 5 years ago.



The Leviathan is one of the researchers at (or affiliated with) Frequency Therapeutics if I am not mistaken.
The Leviathan posted that people with mild to moderate hearing loss still have supporting cells.
No more supporting cells results in profound hearing loss.
(posted 1 month ago on reddit.com).

I wonder if more is known about the effects of NIHL and supporting cells.
Is it possible that noise and time depletes supporting cells.
Is it possible to damage inner ears with noise to such an extend that you are left with profound hearing loss (and thus perhaps no more supporting cells). That has to be accidental. know one in his or her right mind will continue abusing ears all the way to profound hearing loss I would think.
If you suffer from NIHL for a long time, will supporting cells remain?

I think we can all imagine what it means if supporting cells are effected by noise and time.

 

[Fabrikat]

e can all imagine what it means if supporting cells are effected by noise and t

I have thought this too. If one is profoundly deaf in say upper frequencies, to the point where
supporting cells have been killed off, there may well be nothing there to regenerate. And if hair cell death is responsible for tinnitus, no cure will be possible.

I wonder if stem cell treatments are potentially able to grow something in a location, where a small molecule treatment may not.

 

[Frédéric]

One more article about cochlear synaptopathy :

Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta)
https://doi.org/10.1016/j.heares.2017.07.003Get rights and content

Highlights
•Cochlear synaptopathy is an important component of sensorineural hearing loss.
•Cochlear synaptopathy is a primary event following acoustic trauma in primates.
•Primates are resilient to noise-induced hair cell loss and threshold shifts.
•Primates do not appear to be more resilient to synaptopathy than non-primates.
Abstract
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 h. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12–27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50–75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents.

Keywords
Noise-induced hearing loss
Cochlear synapatopathy
Non-human primate
Permanent threshold shift
Temporary threshold shift
Cochlear histopathology
source : http://www.sciencedirect.com/science/article/pii/S0378595517301168

 

[Frédéric]

Another interesting article (too long to copy and paste) :
http://leader.pubs.asha.org/article.aspx?articleid=2643060

 

[Paulmanlike]

Otonomy seems the best bet, repairing both synapse damage along with hair cell regeneration. + oto-311 specifically for tinnitus (let's hope it's for chronic as well)

 

[Aaron123]

One more article about cochlear synaptopathy :

Already posted:
https://www.tinnitustalk.com/thread...ybe-we-can-know-more.3131/page-92#post-260670

 

[Reinier]

I wonder if stem cell treatments are potentially able to grow something in a location

This is one of the possibilities HHF suggested and investigates.
That won't be possible for quit some time I imagine (when also supporting cells are lost).
(if ever).

And if hair cell death is responsible for tinnitus, no cure will be possible.

I lost high frequencies because of ageing. I used to be able to hear line frequencies of old TVs (approximately 16 kHz) easily. (The interesting part is that this 16 kHz did not bother me at all when watching television. You could after all compare this with a tinnitus frequency. I apparently was able to ignore this tone. Why than am I not able to ignore my tinnitus).
That ability to hear this frequency "dissipated" over time. I suspect hair cell loss because of ageing. But this did not give me tinnitus.
But one very loud blast did give me tinnitus.
Therefore I think you can loose hair cells without getting tinnitus.

 

[Paulmanlike]

Already posted:
https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/page-92#post-260670

You can't fool Aaron - knows everything this guy. I wish he could be some sort of moderator for the research section. I respect you highly.

 

[Paulmanlike]

This is one of the possibilities HHF suggested and investigates.
That won't be possible for quit some time I imagine.
(if ever).

I lost high frequencies because of ageing. I used to be able to hear line frequencies of old TVs (approximately 15 kHz) easily.
That ability "dissipated" over time. But this did not give me tinnitus.
One very loud blast did give me tinnitus.
Therefore I think you can loose hair cells without getting tinnitus.

I wonder if gradual hearing loss doesn't cause t because it happens so long, whereas sudden hearing loss does because it happens in a short amount of time. Like the brain has a shorter time to get 'used' to it.

 

[Reinier]

I wonder if gradual hearing loss doesn't cause t because it happens so long, whereas sudden hearing loss does because it happens in a short amount of time. Like the brain has a shorter time to get 'used' to it.

Yes my thoughts too.
Also I think an important part can be anxiety. For me personally this "incident" with loosing part of my hearing in one blast was stressful.

 

[Fabrikat]

I lost high frequencies because of ageing. I used to be able to hear line frequencies of old TVs (approximately 16 kHz) easily.
That ability "dissipated" over time. But this did not give me tinnitus.
One very loud blast did give me tinnitus.
Therefore I think you can loose hair cells without getting tinnitus.

So 'natural' hearing loss caused you no tinnitus, but noise damage did. Any theories why?

 

[Paulmanlike]

Yes my thoughts too.
Also I think an important part can be anxiety. For me personally this "incident" with loosing part of my hearing in one blast was stressful.

I'm also wonderIng if also tinnitus annoyance, distress, anxiety etc is also co-existent with anxiety or anxiety disorders.

I know a handful of people with T who are little concerned with their t without anxiety or anxiety disorders, opposed to me who suffers with anxiety disorder with t.

 

[Paulmanlike]

So 'natural' hearing loss caused you no tinnitus, but noise damage did. Any theories why?

My hypotheses above. Hearing loss that is gradual the brain adapts to it, sudden there is less time as the brain had less time to adapt to it.

 

[Reinier]

So 'natural' hearing loss caused you no tinnitus, but noise damage did. Any theories why?

Anxiety? Brain plasticity?
On the other hand, is noise damage not just accelerated ageing of the hearing system?

 

[Paulmanlike]

Anxiety? Brain plasticity?
On the other hand, is noise damage not just accelerated ageing of the hearing system?

I would agree, natural wear and tear speeded up. Still, tinnitus is not nice though and a cure/treatment would help millions.

 

[Fabrikat]

Anxiety? Brain plasticity?
On the other hand is noise damage not just accelerated ageing of the hearing system?

Probably, but maybe noise damage is worse. There is an inflammatory response of some sort which causes cell death and lesions on nerves. There is something about this physiological reaction that leads to tinnitus, whereas presbycusis may not. Mind you, I suspect genetics has something to do with it too. Why do 70 per cent of the population escape this Diablo?

 

[Paulmanlike]

Maybe 70 per cent don't escape it, they are just more able to tolerate it.

Okay guys let's keep this thread focused on inner hair cell regeneration

 

[tomytl]

Hi there,
so is there a scientific fact, that supporting cells will dissapear after a long time of hair cell absence?