Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Aaron123]

So correct me if i didn't get it well. From the above i understood that when (and if ) those therapies will be available - that means years - there is a big possibility not to work for people like me. I wasn't aware of that to tell you the truth.

Given where we are now, it seems premature to say who might or might not benefit. I don't think anyone knows how many years is too many though presumably the chance of success will go down with the number of years.

 

[acufenero]

Decibel and Otonomy are the places (we know of) to look for synapse repair.

Affichem's working on that, too.

 

[hans01]

Given where we are now, it seems premature to say who might or might not benefit. I don't think anyone knows how many years is too many though presumably the chance of success will go down with the number of years.

Oh that would be sad, I have hearing loss and T since 17 years, just got worse the last years, so i hoped this could still repair my hearing (above 6Khz , where I have 50% loss), really hope one day be able to get rid of T completely, the high hissing is tiresome.

 

[Mortzcent]

This makes frequency treatments look like something to be used after recent hearing damage, kinda sad if you ask me... But i am not gonna judge anything till phase 2 ends.

 

[Aaron123]

Oh that would be sad, I have hearing loss and T since 17 years, just got worse the last years, so i hoped this could still repair my hearing (above 6Khz , where I have 50% loss), really hope one day be able to get rid of T completely, the high hissing is tiresome.

This makes frequency treatments look like something to be used after recent hearing damage, kinda sad if you ask me... But i am not gonna judge anything till phase 2 ends.

I was referring to snyapse repair, not hair cell regeneration.

 

[grate_biff]

Also does Frequency and Audion approaches target somehow those issues?

Not specifically, but this is not an issue with F TX because the dormant cells are already connected/will naturally form synaptic connections to the hearing nerve if/when regeneration of new HC.
So there certainly are lots of ifs and buts here, and believe me I am literally dying to know the answers to these questions myself. I hope, one year from now, we will know a lot more from the F TX phase II trial.

 

[Mortzcent]

Oh, ok my bad

 

[vermillion]

Given where we are now, it seems premature to say who might or might not benefit. I don't think anyone knows how many years is too many though presumably the chance of success will go down with the number of years.

Aaron thank you for taking the time to respond.

In one of your previous posts over frequency's method i found this paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395286/
In the summery it mentions:
"The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments."

Does this mean that the new hair cells reform synapses? I am not yet very familiar with the scientific terminology and i am really interesting to understand the information correctly.

I was also having this difficulty in understanding the differences between different reasons for acquiring HL, especially ototoxicity, in relation to those therapies. Then i came across to this post of yours:

If there are dead hair cells, their approach may work. It won't work on hearing loss due to other types of damage.
Genetic hearing loss may involve only hair cells, but regrowing genetically defective hair cells isn't likely to be much of a solution if the new hair cells are also genetically defective.
Additionally, people are using "ototoxic" in a very non-specific way. If a drug is ototoxic and kills hair cells, then this approach may well work. If it is ototoxic and damages other types of cells in the cochlea, then this approach is very unlikely to work. (And the number of truly ototoxic drugs - drugs that specifically result in hearing loss - is much more limited than people on this forum seem to realize. The leading examples generating the most work are Aminoglycoside antibiotics and cisplatin, a chemotherapy drug.)

So this somehow makes things a bit more clear to me. I suppose ototoxicity could damage also those progenitor cells?

 

[vermillion]

Not specifically, but this is not an issue with F TX because the dormant cells are already connected/will naturally form synaptic connections to the hearing nerve if/when regeneration of new HC.
So there certainly are lots of ifs and buts here, and believe me I am literally dying to know the answers to these questions myself. I hope, one year from now, we will know a lot more from the F TX phase II trial.

Thank you @grate_biff. I just read your post and if you see above i am asking Aaron over this, in regard to that paper i included. Yes there's lot of impatience and i get that time counts here.

 

[Paulmanlike]

So if an effective tinnitus treatment comes about (speculation here) from Decibel and Otonomy through synapse repair, the chance will become less of it being curable as long as you've had it.

Say if these nerves die after the synapses are damaged, are they not looking at regenerating nerves or creating new ones or am I well over thinking it and it's just not possible?

 

[hans01]

I was referring to snyapse repair, not hair cell regeneration.

But how to know if synapses are dead or just hair cells ?

 

[GGG-DG]

The precise window isn't known - certainly not for humans. The issue is that after the death of the synapse, the nerve itself eventually dies but that death is not immediate. I believe the time frame is "months to years". See here for more information: https://www.nature.com/articles/srep24907

Also, from the article in your link:

"Given that cochlear implants can continue to provide useful hearing for years after hair cell loss, these long-surviving neurons must remain electrically excitable and appropriately connected to their central targets10. Thus, in many types of sensorineural hearing loss, there is a long therapeutic window wherein a treatment to elicit neurite outgrowth could reconnect silenced cochlear ganglion cells with hair cells, and thereby potentially improve speech in noise performance and reduce tinnitus."

 

[lapidus]

No. Decibel and Otonomy are the places (we know of) to look for synapse repair.

What about Hough Ear Institute?

 

[jeff W]

The precise window isn't known - certainly not for humans. The issue is that after the death of the synapse, the nerve itself eventually dies but that death is not immediate. I believe the time frame is "months to years". See here for more information: https://www.nature.com/articles/srep24907

I

So correct me if i didn't get it well. From the above i understood that when (and if ) those therapies will be available - that means years - there is a big possibility not to work for people like me. I wasn't aware of that to tell you the truth.

@vermillion
Would 20 or 30 years sound better?

Source: Saager & others (2017) referencing a 2002 paper by Felix, H., Pollak, A., Gleeson, M. & Johnsson

 

[vermillion]

I



@vermillion
Would 20 or 30 years sound better?
View attachment 14295
Source: Saager & others (2017) referencing a 2002 paper by Felix, H., Pollak, A., Gleeson, M. & Johnsson

That's a hopeful citation

 

[Joeymeatballs]

So, sorry a potentially bad question but I am confused, are synapse repair and hair cell regeneration connected? As in, say Frequencies' trials go well and helps people with tinnitus, will their hair cell regeneration only work if the synapses haven't died?

 

[Aaron123]

So, sorry a potentially bad question but I am confused, are synapse repair and hair cell regeneration connected?

Not directly, no. Frequency is working on hair cell regeneration but not synapse repair (that we know of).

s in, say Frequencies' trials go well and helps people with tinnitus, will their hair cell regeneration only work if the synapses haven't died?

If their approach works, new hair cells will be generated. The hope/thought is that new synapses will form to connect to those new hair cells. I believe nothing will happen in cases where the hair cell is intact but the synapse is dead.

 

[Joeymeatballs]

@Aaron123 Hm, so what will happen to the company if the synapses don't end up forming? I assume that their main target demographic of HL patients need those synapses to reform too, right?

Thank you for the reply. Here's to hoping Decibel drops some sort of exciting news soon

 

[Aaron123]

so what will happen to the company if the synapses don't end up forming?

They likely will move on to other conditions. If they are right, they should form. The idea is that they are attempting to restart a "natural" process, and part of that process is the formation of these synapses.

 

[jcloth]

Not directly, no. Frequency is working on hair cell regeneration but not synapse repair (that we know of).


If their approach works, new hair cells will be generated. The hope/thought is that new synapses will form to connect to those new hair cells. I believe nothing will happen in cases where the hair cell is intact but the synapse is dead.

My hopeful speculation (based on nothing) is that if these deafferented hair cells are near to missing hair cells, the regeneration process might release neurotrophic factors or other signals that cause these to re-synapse as well.

 

[Paulmanlike]

I contacted Rescue Hearing and here's what I asked them:

Hi do you guys expect to eliminate tinnitus by regenerating inner hair cells?


It took a few months but then I got this back:

I apologize for the tardiness of my reply as we have been quite busy. Our initial therapies will target progressive hearing loss. We will apply our learnings for these efforts to other indications such as tinnitus in our future products. Thank you for your interest in Rescue Hearing Inc.


I didn't know whether this was the best thread to post it and to be honest I forgot what company they actually are or what they're doing as there's so much going on at the moment.

 

[Flamingo1]

I contacted Rescue Hearing and here's [what they said] :

I apologize for the tardiness of my reply as we have been quite busy. Our initial therapies will target progressive hearing loss. We will apply our learnings for these efforts to other indications such as tinnitus in our future products. Thank you for your interest in Rescue Hearing Inc.

No idea what this means.

 

[Autumnly]

What about Hough Ear Institute?

Hough Ear Institute is working on regenerating hair cells and restoring the connection between the auditory nerve and the hair cells:

"Hough Ear Institute has created silencing RNA (siRNA) technology that regenerates the inner ear hair cells destroyed by noise induced hearing loss. We are using silencing RNA technology to change supporting inner ear hair cells into sensory hair cells essential to hearing. Along with this, we are also working on restoring the connection between the auditory nerve and the hair cells that are disconnected when the hair cells die. We have both culture dish and live animal data that shows we can regenerate these fine nerve connections and reconnect them to hair cells for hearing restoration. "

 

[Reinier]

Hm, so what will happen to the company if the synapses don't end up forming?

This is from one of their research papers:
"The Lgr5-expressing cells differentiate into hair cells in high yield.
From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity."
I understand that these LGR5-expressing cells are the progenitor cells. So, stem cell like.

 

[grate_biff]

absence of induction.

What does that mean?
absence of induced HL?

 

[Berik]

From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction.

how many is a mouse born with? 11,500 haircells sounds as a lot (a lot of generated hc)

 

[Autumnly]

All I could find via google is this:

"There are approximately 15,000 sensory hair cells in the mouse inner ear cochlea."

Please correct me if the statement above is wrong!

 

[Berik]

All I could find via google is this:

"There are approximately 15,000 sensory hair cells in the mouse inner ear cochlea."

Please correct me if the statement above is wrong.

Interesting; similair to humar that would be then. And with 11,500 HC regenerated, that would mean 76% grew back?

 

[Joeymeatballs]

This is from one of their research papers:
"The Lgr5-expressing cells differentiate into hair cells in high yield.
From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity."
I understand that these LGR5-expressing cells are the progenitor cells. So, stem cell like.

Awesome, thank you.

 

[Cam Cam]

so what happens with people who have both synapse damage and hair cell damage? Do they need both medical approaches in theory by decibel and FX? How do we even know what type of damage a HUMAN has? Where are the imaging devices because at the moment a hearing test seems vastly, VASTLY outdated and we're just taking stabs in the dark with these future approaches.