Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[WillBeNimble]

Was basing it off kyorins pipeline. It's all preclinical and doesn't go into what it even is though.I mean, it makes sense, but would be nice to know what they're going to try that's different.

 

[Thuan]

That explanation with the neutrophils and anti-inflammation doesn't make much sense in restoring SSHL unless it's used as an early preventative measure (since active infection's inflammation do damage the ear). Otherwise, it sounds like BS to boost public relations.

 

[tommyd87]

@WillBeNimble it is looking like that the treatment at the bottom box is completely different to this hearing loss drug.

In fact I feel that this is just a note about this drug being in development.

 

[FGG]

@WillBeNimble

It's not in Kyorin's pipeline, it's Otonomy's drug. Kyorin are just funding development outside the US (like Astellas is with Frequency). Kyorin has an unrelated anti-inflammatory asthma drug you may be referring to.

Otonomy have said OTO-6xx is a hair cell regeneration drug for severe losses. More info here:

https://investors.otonomy.com/static-files/7422fbf3-e07b-4b71-a398-fb578ab858e1

 

[WillBeNimble]

@WillBeNimble

It's not in Kyorin's pipeline, it's Otonomy's drug. Kyorin are just funding development outside the US (like Astellas is with Frequency). Kyorin has an unrelated anti-inflammatory asthma drug you may be referring to.

Otonomy have said OTO-6xx is a hair cell regeneration drug for severe losses. More info here:

https://investors.otonomy.com/static-files/7422fbf3-e07b-4b71-a398-fb578ab858e1

Thanks FGG, yeah, I realized that a bit later. Makes sense, I was expecting that there was some data they went off of, though. It's probably all confidential right now, though.

 

[d'Wooluf]

It's not in Kyorin's pipeline, it's Otonomy's drug. Kyorin are just funding development outside the US (like Astellas is with Frequency).

I read it the opposite. Otonomy are paying Kyorin.

 

[tommyd87]

I read it the opposite. Otonomy are paying Kyorin.

I think that this correct. Otonomy has made an agreement with Kyorin to produce and provide the drug to those outside the US and in return Otonomy are given royalties for doing so.

https://seekingalpha.com/news/3598881-otonomy-up-7-on-license-pact-kyorin-for-hearing-loss-program

 

[Greg Sacramento]

Interesting article, where with other support and reference articles, seems to express one of a few important area of needed focus.

In this context, future studies will be needed to also identify the dedicated output neurons and associated ascending circuits needed to process centrally the peripheral information encoded by each individual SG neuron type.

https://www.nature.com/articles/s41...OHYMfKL8jceMmZ4ew9-Eh1hwjPG9JjXcpJuGvjkFuPOs=

 

[Jurger]

It talks about anti-inflammatory and preventing neutrophile migration. How does this generate new hair cells?

Great news, whatever the method. The more options the better it is for patients. Eventually something will work, or multiple drugs that are complimentary to each other.

 

[serendipity1996]

This new study from The Lancet was retweeted by Frequency Therapeutics. Hearing loss is identified as the no. 1 potentially modifiable risk factor for dementia. Even more impetus for FX-322 to be approved as soon as possible!

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30367-6/fulltext

 

[tomytl]

It's nice to see, that one more company does drive a regeneration programm to the clinic.
But this will take years even they start with human Phase 1 trials.
Let's hope that Frequency or Audion come to the market within the next 5 years.

 

[tomytl]

Not sure if posted before:
https://hms.harvard.edu/news/dramatic-effect

 

[Diesel]

Not sure if posted before:
https://hms.harvard.edu/news/dramatic-effect

Interesting. If I am understanding it correctly, it may have an effect on restoring broken synapses between hair cells and the nerve?

 

[tomytl]

What happend to the Novartis Atoh1 ... what can we read from this?
Last Update was in July 2020

I can't understand what's next or what's the result.

https://clinicaltrials.gov/ct2/show/NCT02132130

 

[Thuan]

Not sure if posted before:
https://hms.harvard.edu/news/dramatic-effect

Here's also a research article of biphosphonates in regards to cochlear synapses by Harvard Medical School: https://www.frontiersin.org/articles/10.3389/fnmol.2020.00087/full

Biphosphonates have been used for cancer treatment and some other bone disease, osteoporosis, but it's been known to have very severe side effects, such as jaw necrosis (your jaw bones literally dies) and in extreme cases coma. It is quite scary.

 

[tommyd87]

What happend to the Novartis Atoh1 ... what can we read from this?
Last Update was in July 2020

I can't understand what's next or what's the result.

https://clinicaltrials.gov/ct2/show/NCT02132130

Apparently it wasn't doing enough for what they wanted it to do although apparently they got results in some patients.

 

[FGG]

What happend to the Novartis Atoh1 ... what can we read from this?
Last Update was in July 2020

I can't understand what's next or what's the result.

https://clinicaltrials.gov/ct2/show/NCT02132130

Here is the thread on Novartis' drug:

https://www.tinnitustalk.com/thread...ate-may-2016-trial-is-again-continuing.12949/

 

[d'Wooluf]

Not sure if posted before:
https://hms.harvard.edu/news/dramatic-effect

Some discussion here:

https://www.tinnitustalk.com/thread...mic-administration-of-a-bisphosphonate.41735/

 

[xyz]

Not sure if posted before:
https://hms.harvard.edu/news/dramatic-effect

Nice find.

The team further suggested that their finding provides possible mechanisms that could explain why some patients in the clinic have improved their ability to recognize speech after bisphosphonate treatment.

So if this bisphosphonate is already in use clinically this clinical trial process can be probably pushed through much faster?

Interesting. If I am understanding it correctly, it may have an effect on restoring broken synapses between hair cells and the nerve?

Yes, as it states in the article:

The scientists administered bisphosphonates to mice 24 hours after noise exposure. They found that the medication had a dramatic effect at regenerating the synapses between inner hair cells and spiral ganglion neurons found in the ear, and restoring cochlear function.

I am just wondering if this is for acute or chronic tinnitus.

 

[Thuan]

Nice find.

The team further suggested that their finding provides possible mechanisms that could explain why some patients in the clinic have improved their ability to recognize speech after bisphosphonate treatment.

So if this bisphosphonate is already in use clinically this clinical trial process can be probably pushed through much faster?

Yes, as it states in the article:

The scientists administered bisphosphonates to mice 24 hours after noise exposure. They found that the medication had a dramatic effect at regenerating the synapses between inner hair cells and spiral ganglion neurons found in the ear, and restoring cochlear function.

I am just wondering if this is for acute or chronic tinnitus.

Unfortunately, 24 hours is not chronic.

 

[d'Wooluf]

Unfortunately, 24 hours is not chronic.

A previous study analysed data going back 5 years or more and found some evidence that hearing loss stabilised or slightly improved over that time. It wasn't a very rigorous study and I don't have a link to it right now. Sorry.

 

[xyz]

Unfortunately, 24 hours is not chronic.

Yes, but the ones who got treated with this bisphosphonate probably did not get treated for sudden hearing loss with it, so probably it will work also for more chronic cases. Hopefully the BDNF OTO-413 has less side effects and also repairs our synapses.

 

[BBakkers]

I've lost track of which research is going on. There is a lot going on. I can remember somoene made a nice overview of all the type of research (modulation, regeneration, etc). Do we have thread for this? Like a research track thread overview?

 

[tommyd87]

https://elifesciences.org/articles/55249

The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing

Interesting, however it seems that this research of looking inside the cochlear has somewhat been done already by other companies such as Frequency Therapeutics. In fact it seems that many of these university based research organisations are well behind when compared to the private companies engaging in research in this sphere, though I could be wrong, and this might be novel.

 

[Reinier]

There is much more to age related hearing loss than hair cell loss alone.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(20)30169-7

 

[WillBeNimble]

There is much more to age related hearing loss than hair cell loss alone.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(20)30169-7

Do you mean that age related hearing loss is not just hair loss, or do you mean that loss is connected to cognitive decline?

Because a study on hearing loss and such just released makes it seem like it is just hair loss from NIHL.

 

[Reinier]

Do you mean that age related hearing loss is not just hair loss, or do you mean that loss is connected to cognitive decline?

Unfortunately we keep reading that hearing loss could contribute to cognitive decline.
I was just looking at the mechanism of age related hearing loss in this publication.

From what I can understand, age related hearing loss is not just hair cell loss. It is much more complicated.

 

[Diesel]

Unfortunately we keep reading that hearing loss could contribute to cognitive decline.
I was just looking at the mechanism of age related hearing loss in this publication.

From what I can understand, age related hearing loss is not just hair cell loss. It is much more complicated.

Might want to take a look at:

https://hms.harvard.edu/news/upending-dogma

and

https://www.jneurosci.org/content/40/33/6357

 

[WillBeNimble]

Unfortunately we keep reading that hearing loss could contribute to cognitive decline.
I was just looking at the mechanism of age related hearing loss in this publication.

From what I can understand, age related hearing loss is not just hair cell loss. It is much more complicated.

https://hms.harvard.edu/news/upending-dogma

Turns out it is by and large just hair cell loss. With new technology, they were able to see the individual hair cells more and identify the losses. The model for human hearing that was made from whatever ancient studies they pulled this dogma from always outpaced the scaled animal odels hearing loss by a large margin. Researchers at the time though couldn't find the cause and just chalked it up to our hearing batteries just being worse. It's really just that we're damaging our ears with how loud everything is.

 

[serendipity1996]

https://hms.harvard.edu/news/upending-dogma

Turns out it is by and large just hair cell loss. With new technology, they were able to see the individual hair cells more and identify the losses. The model for human hearing that was made from whatever ancient studies they pulled this dogma from always outpaced the scaled animal odels hearing loss by a large margin. Researchers at the time though couldn't find the cause and just chalked it up to our hearing batteries just being worse. It's really just that we're damaging our ears with how loud everything is.

Indeed. Also I can't remember exactly where I read it but they found that people who live in tribal societies away from the industrialised world displayed significantly better hearing as they aged compared to their counterparts in noisy industrialised societies.