Audion Therapeutics Trial

[Michael Larsen]

My hearing loss is a problem but I won't apply : Audion's trial will leave you with fewer (or no) supporting cells left. I want to be able to apply to Frequency's, which targets a more conservative approach. If Frequency fails and Audion succeeds, I'll still be able to benefit from Audion's drug, which will be closer to the market then.

What does it mean if you do not have any supporting cells left? And who would then benefit from participating in the trial?

 

[Berik]

What does it mean if you do not have any supporting cells left? And who would then benefit from participating in the trial?

The drug works by triggering supporting cells to convert into hair cells. Frequency on the other hand, has a drug which triggers multiplying of supporting cells before converting into hair cells.

 

[leledany]

The old and damaged heairing cell what they will do?

 

[Samir]

The drug works by triggering supporting cells to convert into hair cells. Frequency on the other hand, has a drug which triggers multiplying of supporting cells before converting into hair cells.

That is correct!

On the other hand, it will be close to impossible to tell who has supporting cells left and who does not. This is another reason why we need better diagnostic tools. Preferably some kind of imaging technology.

Although there are people working on just that, we are still far off from being able to visually inspect what is going on inside the cochlea, who has supporting cells and who does not.

Until we can objectively and accurately assess the damage inside the cochlea of a living person, all forms of therapies will be blindshots, based on pathophysiological and histological findings in the labs. Hopefully scientists will have learned a lot this way, enough to be able to devise a beneficial therapy. But you still have that problem of not knowing who a certain therapy will benefit the most, and initially these therapies will be costly.

So we need to find a way to peek inside the cochlea. Not only would it be beneficial to patients, it would also unlock new opportunities for investigators.

 

[grate_biff]

So we need to find a way to peek inside the cochlea as soon as possibl

One should think a combination of X-ray technology and microscope would do the trick. But I bet its not that easy. Or did I just solve it right there

btw. This video show us pretty much how is it build. Quite facinating!

 

[Berik]

That is correct!

On the other hand, it will be close to impossible to tell who has supporting cells left and who does not. This is another reason why we need better diagnostic tools. Preferably some kind of imaging technology.

Although there are people working on just that, we are still far off from being able to visually inspect what is going on inside the cochlea, who has supporting cells and who does not.

Until we can objectively and accurately assess the damage inside the cochlea of a living person, all forms of therapies will be blindshots, based on pathophysiological and histological findings in the labs. Hopefully scientists will have learned a lot this way, enough to be able to devise a beneficial therapy. But you still have that problem of not knowing who a certain therapy will benefit the most, and initially these therapies will be costly.

So we need to find a way to peek inside the cochlea. Not only would it be beneficial to patients, it would also unlock new opportunities for investigators.

With the combination of a GSK3 inhibitor to activate the Wnt signaling pathway and a histone deacetylase (HDAC) inhibitor to activate gene transcription, the research team achieved >2000-fold expansion of cochlear supporting cells compared to previous approaches.

src: http://www.frequencytx.com/news-events/pr-02-21-2017.php

If above statement of FX is true, I would just hope that a few cells remaining would be sufficient to trigger the multiplication to several thounds so it would work. Undoubedtly you know more about it then me, I think I do not want to know to much about it and just hope for it to work for my tinnitus. First find the cure, then later on figure out why it works. Like with Lithium; it works as anti-depressant but they don't know why.

 

[Samir]

One should think a combination of X-ray technology and microscope would do the trick.

Radiomicroscopy! We already have radiosurgery! So sure, why not! Dare to think the impossible!





http://www.daretothinktheimpossible.com/

New cone-beam CT as well as ultra high resolution CT scanners are coming to the market.

http://medicalphysicsweb.org/cws/article/research/69215

https://www.isct.org/computed-tomography-blog/2017/6/16/cutting-edge-ct-news-from-isct17

These technologies will enable scientists and clinicians to get a new level of details when imaging the inner ear, as well as other parts of the body. Minimizing the components and making them more energy efficient will set the bar even higher.

 

[Berik]

The trial should have started last month, with testing on humans. Anybody has some insight knowledge? Exciting to think people currently could actually be regaining some of their hearing through this..

 

[acufenero]

The trial should have started last month, with testing on humans. Anybody has some insight knowledge? Exciting to think people currently could actually be regaining some of their hearing through this..

Actually, the recruiting hasn't started yet according to the website.

 

[Berik]

Actually, the recruiting hasn't started yet according to the website.

Makes me curious. As per below link in this reply, they would start in August.

Could it be above it not properly up-to-date? As in, http://www.audiontherapeutics.com/, ever looked at their website footer?:

© Copyright Company Name 2011. All rights reserved.

https://www.actiononhearingloss.org...earing-loss-to-take-part-in-a-clinical-trial/

 

[Samir]

ever looked at their website footer?

Yeah, I saw that. That's because they don't have the time nor people to maintain such things. The website was probably done in 2011 by some freelance web developer and it's been left in that state since.

The most important thing for these companies is that they have a web presence. That's important for any company today. But especially if you seek investors with deep pockets. What a better way to showcase who you are and what you do then to have a website.

Of course some of them have more people and more money to invest in such things. Like the website of Frequency Therapeutics and Decibel Therapeutics. Have you seen Audio Cure's website lately? They did a complete remake recently. The new site looks much cleaner and modern. Perhaps Audion will do something like that soon as well.

So I would not give too much importance to that.

 

[VRZ78]

Recruitment start date (planned) is 15/09/17

 

[Reinier]

Does anyone know if this is correct?
http://www.ibtimes.com.au/dutch-company-hold-human-clinical-trial-reverse-hearing-loss-1522898
Quote: "For the human trial, Audion would use compounds developed by pharmaceutical giant Eli Lilly and with Frequency Therapeutics which would develop the treatment – using a tube or piece of foam in the middle ear to stimulate regrowth of hair cells damaged by sound."
End quote.
Why is Frequency Therapeutics mentioned?
Frequency Therapeutics is following a different approach from Audion/Eli Lilly if I remember correct. Is there collaboration between Audion and Frequency Therapeutics?

 

[Casper]

Does anyone know if this is correct?
http://www.ibtimes.com.au/dutch-company-hold-human-clinical-trial-reverse-hearing-loss-1522898
Quote: "For the human trial, Audion would use compounds developed by pharmaceutical giant Eli Lilly and with Frequency Therapeutics which would develop the treatment – using a tube or piece of foam in the middle ear to stimulate regrowth of hair cells damaged by sound."
End quote.
Why is Frequency Therapeutics mentioned?
Frequency Therapeutics is following a different approach from Audion/Eli Lilly if I remember correct. Is there collaboration between Audion and Frequency Therapeutics?

Hey @Reinier, thanks for posting and that's a really good question. I did some searching, and I came across this article from 2016 (emphasis mine):

Dutch company Audion Therapeutics, of which Edge is a part, is working on a proof of concept for regeneration of human-ear hair cells. They are using compounds developed by pharmaceutical giant Eli Lilly and applying them locally to the inner ear.

And later in the same article:

Frequency Therapeutics declined an interview on the subject on the basis that they are in "stealth mode" pending a big research announcement.

It sounds like this collaboration is a new development. The following is purely my own speculation, but I suspect that Audion Therapeutics wants to take advantage of Frequency Therapeutics's proprietary local drug-delivery methods, which would have been developed and announced after Audion made the initial press release linked above.

 

[Berik]

But then the question: do they use different methods for inducing haircell growth from supporting cells? (or both Notch) My concern would be if audion trials fail, does this mean FX method is also compromised?

 

[acufenero]

But then the question: do they use different methods for inducing haircell growth from supporting cells? (or both Notch) My concern would be if audion trials fail, does this mean FX method is also compromised?

I think they are quite different methods:

 

[Jim51042]

But then the question: do they use different methods for inducing haircell growth from supporting cells? (or both Notch) My concern would be if audion trials fail, does this mean FX method is also compromised?

Yes they use different methods. If Audion is successful FX would likely be even much more successful

 

[threefirefour]

3 more days. I'm kinda hyped

 

[Coleoptere]

3 more days. I'm kinda hyped

Yes, but it will take a while before these resultaten will be published.

http://www.isrctn.com/ISRCTN59733689

The intended publish date is 31-1-2020 according to this link. That is late for a test which is supposed to be finished mid 2018.

 

[Jim51042]

The intended publish date is 31-1-2020

The informal assessment will leak long before that. They also may decide to push the publish date earlier.

 

[acufenero]

The informal assessment will leak long before that. They also may decide to push the publish date earlier.

Agree, especially if the outcomes are proving efficacy.

 

[Samir]

I forgot to update you guys on my previous request to the leaders of the clinical trial.

We have received more information re: international patients and unfortunately we will not be able to recruit you on to the study at this time. We will be in touch if this changes.

So that's that. I wish them luck with the trial and hope for a success.

 

[Berik]

I think they are quite different methods:

View attachment 13618

At the same time, to prevent the cells from differentiating too soon, the researchers also exposed the cells to molecules that activate another signaling pathway known as Notch.

https://www.eurekalert.org/pub_releases/2017-02/miot-dtc021717.php

From above I understand FX also uses Notch in their approach, is this correct?

 

[Aaron123]

Does anyone know if this is correct?
http://www.ibtimes.com.au/dutch-company-hold-human-clinical-trial-reverse-hearing-loss-1522898
Quote: "For the human trial, Audion would use compounds developed by pharmaceutical giant Eli Lilly and with Frequency Therapeutics which would develop the treatment – using a tube or piece of foam in the middle ear to stimulate regrowth of hair cells damaged by sound."
End quote.
Why is Frequency Therapeutics mentioned?
Frequency Therapeutics is following a different approach from Audion/Eli Lilly if I remember correct. Is there collaboration between Audion and Frequency Therapeutics?

That article is over a year old. There's no evidence that Frequency and Audion are working together, and I can't imagine why it would make sense for Frequency at this point. That article is very similar to an article in the atlantic that came out around the same time. It was mentioned here around the time it was published: https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/page-47#post-194157

It sounds like this collaboration is a new development.

All of these articles are over a year old so they don't report a new development.

The following is purely my own speculation, but I suspect that Audion Therapeutics wants to take advantage of Frequency Therapeutics's proprietary local drug-delivery methods,

Frequency does not - to my knowledge - have a proprietary drug delivery system, and one isn't mentioned in your link. They do - or are planning to do - a simple injection through the ear drum, but such an injection is not proprietary. Their PCA platform is of course proprietary but that isn't a delivery method.

But then the question: do they use different methods for inducing haircell growth from supporting cells? (or both Notch) My concern would be if audion trials fail, does this mean FX method is also compromised?

Frequency is attempting to do 2 things: 1) cause supporting cells to multiply and 2) cause some of the multiplied supporting cells to become hair cells. Audion is attempting to cause supporting cells to become hair cells without first creating new supporting cells. (This is why there is concern about the depletion of supporting cells in Audion's approach.) In both cases the differentiation of supporting cells into hair cells relies on a gamma secretase inhibitor though the specifics are a bit different in each case. So there will be information in the Audion results that may tell us something about Frequency but a failure by Audion does not necessarily mean Frequency will fail though it would be concerning. (I've attempted to clarify what was done in each experiment in the McLean et al paper from earlier this year in a post in the thread on Frequency.)

From above I understand FX also uses Notch in their approach, is this correct?

Yes, Frequency relies on Notch inhibition in the differentiation of supporting cells into hair cells.

 

[nills]

Publishing findings in Jan 2020

http://www.isrctn.com/ISRCTN59733689

from the paper:


Secondary outcome measures
1. Change in hearing is measured using Pure Tone Audiometry (PTA) (dBHL) at baseline and week 12
2. Balance is measured using several balance tests at visit one, two, and three
3. Tinnitus measured using a questionnaire at visit one, two and three

 

[Jim51042]

Ok today is their recruitment start date! Has that slipped or are they a go?

 

[Iliasp]

Seems on schedule

 

[Paulmanlike]

Actually, the recruiting hasn't started yet according to the website.

It says now it is recruiting but on the regain our hearing website says not recruiting yet.

Hopefully going as planned!!

 

[Coleoptere]

@Samir already requested for being recruited around 7 post up on this page:

https://www.tinnitustalk.com/threads/audion-therapeutics-trial.21830/page-3#post-275531

So if you want to participate ....

 

[vermillion]

Do you believe that hearing aid companies are able to block/affect the results of those trials 'under the table' in order not to loose their profits? A possible success would be devastating for them.