Inner Ear Hair Cell Regeneration — Maybe We Can Know More

My educated guess is Acousia Therapeutics! It's too obvious to miss! They have a direct connection to Tübingen. Or did everyone here miss the fact that Tübingen is a site of interest for hearing restoration in Germany? The fact that professor Löwenheim is based in Tübingen? The fact that he founded Otogene AG in Tübingen? One of the first companies in the world to even attempt to develop therapies for hearing restoration? The fact that professor Löwenheim founded Acousia which also happens to be registered in Tübingen?

So yeah... so much for guessing! It's too easy.

@vaka was probably at the "Klinikum", which is a teaching hospital and a home to the medical faculty of the Eberhard Karls university in Tübingen.

Do you have a source for this?

Compared to everyone else? Why?

Ask to participate in the trial, yes. We can all do that. But qualify for it? I don't think so! Most of these trials only enroll people with severe to profound hearing loss. I don't think there are that many of us here with that level of hearing loss.

Acute hearing loss does not mean they will hurry to run the trial and develop a treatment. Unfortunately!

Deutsche qualität!

Could you please remind me what paper that was?

No! They will be absorbed by the body. But it would help to know just how far that process has gone, following an acoustic trauma for example, before administering the therapeutic agent. To this end we will need something better than the audiometer. Something to the likes of a µOCT endoscope to assess the cellular damage.

You sure know how to ask complicated questions!

I would say Yes and No to this. Again, this calls for a diagnostic tool that can assess the cellular damage, prior to therapy. The body needs to be given time to bury its dead. Does that make sense?

Otherwise it would be like trying to bury a dead person in an occupied grave, or trying to wake the dead where the living stand if you enjoy that version better. Zombies! Woohoho! Think of crumbling ground and a zombie crawling up under your feet!

The body has potential to bury its dead. It's doing that all the time. It's just that, in many parts of the body this is a natural process where old cells die off and new cells are born. While in case of inner ear, this does not happen, and we don't have a tool to see what's going on in there. Not without injuring the patient in the process. So we don't really know what it looks like in there when we administer the therapeutic agent.

If the body has absorbed the dead cells, the new cells will rise from where the old cells used to be. If not, then the new cells will sidestep the dead so to speak and rise next to them, leaving the dead ones to be processed. The new cells would rise where the previously dead and processed cells stood. So you would have a mix of old, dead and new cells. That's why I think the new cells don't line up nicely when you look at pictures from the microscope.

This, I think, will ultimately lead to mixed results from the early regenerative therapies. So we may need to repeat the therapy once the old and dead cells have been absorbed by the body, if they were not absorbed by the time of first therapy.

These things are more complicated than one would expect. That's why we need more time and more research done to perfect the therapy. There are still a lot of cellular and molecular mechanisms that we don't understand. But the first therapies will be out there in the next few years, no doubt. I just think we need to be more cautious about what to expect from these.

It's not the synapses themselves that are responsible for T and H. It's spiral ganglion neurons from which they are projected. I just felt the need to defend the synapses!

Don't only look at the picture. Read the text as well and try to find out how long after the damage the picture was taken.

They turn into Schrödinger's cat!

 

It's not too difficult to reach the cochlea if you are violent enough and use an invasive approach. People get cochlear implants every day all around the world. The only way to that is by reaching into the cochlea. There are three ways to implant the electrode.

• A: Making a hole in the round window.
• B: Making a hole in the round window and enlarging it.
• C: Removing the stapes and making a hole in the oval window.

Of these options, option C is the worst! Not only is it most invasive, it also causes most damage inside the cochlea and you can get endolymphatic hydrops.

It's the less invasive, or non-invasive, diligent approach that's difficult. That's contrary to what I read about Novartis/GenVec, because its said that they make a hole in the cochlea with a laser. For therapeutic, non-invasive approaches, the round window membrane is the best route of access. It's this approach that I would like to see become a standard procedure in the future. Non-invasive! Perfect! I don't need no hole drilling and more damage, thank you.

They already know that Atoh1 is important for hair cell formation. But it's not enough to just generate a bunch of hair cells at random locations. You need to control the process. Here are a few things to consider.

• A: Make hair cells grow.
• B: Stop hair cells from growing.
• C: Grow the right kind of cell at right location.
• D: Orientate the cells the right way.

Think of driving a car! Simple! Right? Well, consider what's involved.

• Turning the car on
• Turning the car off
• Giving it gas
• Clutching
• Shifting gears
• Making a right turn
• Making a left turn
• Controlling the speed
• Making a controlled stop
• Controlling a hard break
• Going in reverse
• Putting on parking break

Making a car run in a straight line does not help anyone! Not the driver inside the car, nor the curious observers outside, wondering what he's up to.

These things may seem like simple to someone who knows how to drive a car. That's because they have learned to automate the whole process. Using this analogy in hearing restoration, I would say we know how to turn the engine on and off and give it gas. We are still learning how to clutch, shift gears, control the speed and make turns. Well actually, we are learning all these things now... but in reverse! That's regenerative hearing restoration - learning to drive a car backwards!

Seriously... the sheer complexities of these processes, when you look at it at a deeper level, it's mind-boggling! No wonder we still don't have a treatment yet. But we are making progress, and that is positive. Step by step! One thing at a time. One thing leads to another. That's how science works. You have to crawl before you can walk.

 

What study are you referring to? I'm sure they have investigated this. I think Aaron posted a link just a few posts earlier. But if you are a bird or a human doesn't matter, you still need to allow time for the body to take care of the dead cells. The only difference between us and the birds is that they can naturally regrow their hair cells while we cannot. And of course, birds can fly!

 

This is something we are still learning about.
http://www.jneurosci.org/content/30/37/12545

I think so, yes. Once the dead ones have been cleared.

I don't think so.

http://www.the-scientist.com/?articles.view/articleNo/43806/title/Aural-History/

 

@acufenero Ah yes! This was quite significant indeed.

I am not sure if it has been posted earlier, but Public Radio International just posted an article on Frequency based on a previous interview with Jeff Karp in one of their Science Friday episodes.

https://www.pri.org/stories/2017-03...earing-loss-regenerating-hair-cells-inner-ear

 

By their way of counting, it should take forever for the trail to begin.

I'm not sure I can entrust my ears to someone who doesn't appear to know how to subtract two numbers.

The PRI radio interview?

Correct! This is my understanding as well. Not exactly sure what they mean by intestinal lining. Intestinal epithelium? Either way! It's supposedly one of the most regenerative tissues in the human body. So they studied it closely to reveal it's secrets. So yeah, that's how they came up with the molecules that can trigger cell proliferation and differentiation.

This is stem cell therapy. But instead of culturing cells in a dish and transplanting them into the ear, you are using molecules to trigger the process inside the ear, using these progenitor cells. Progenitor cells exist inside the ear. Progenitor cells are similar in concept to stem cells, sometimes used as a synonym for a stem cell. They can specialize to become the type of cell you need, in this case hair cells.

The progenitor cells and the drug molecules do. My understanding is that these progenitor cells exist throughout the epithelium, and molecular biologists and bio chemists know how to target them using different advanced techniques like cell signaling.

Have you considered becoming a biologist? Or bio chemist?

It is complicated! If you really want to understand it at that kind of level you really have to study the relevant biology and chemistry.

Me too! But all we can really do is wait. Let them do their work. I am confident that we will see the first therapy within the next 5 years. Frequency may be the first to pull it off, or some other company. Whoever does it first, I'm sure it will happen within the next 5 years.

I like that! Steam...

Already posted! But thanks anyway!

I think the original link to the podcast from February, on which the article is based on, has already been posted here. But we can never get enough of Frequency!

Same here! Like I said, we can never get enough of Frequency!

It feels good to see how everyone is excited by the progress and the research into hair cell regeneration. Many articles are appearing covering companies like Frequency. It's almost becoming viral! So much so that authors don't seem to have time to subtract the numbers to get an up to date estimate of when the trail will begin. It's always "the trial starts in 18 months".

Can we please have a web based counter implemented on the forum that counts down to the Frequency trial? That would be fun, but also useful. That seems like a nice way to track these trials.

 

They are! Why do you think they studied the intestinal lining first? If you want to climb a mountain you have to learn to walk first. The intestinal stem cells were used as an inroad to developing molecules for the ear.

What kind of damage did this person have? Was it only sensory damage? Maybe some nerve damage?

This may not be that much different than the regeneration of the intestinal lining. The human body does have regenerative capacity, just not the kind that people with hearing loss wish for.

I don't know about the smell receptors, but the nerve responsible for smell has natural regenerative property. It's called the olfactory nerve or cranial nerve 1. It's the only cranial nerve that has regenerative property! Unfortunately, the vestibulocochlear nerve, or the cranial nerve 8, has none.

Yeah, I think it's very likely that we may need to retrain our brains to make use of the new sensory hair cells. This may happen naturally, or we may need to make an active rehabilitation program.

 

That depends on how this thing progresses. If I can wait out and stand this, I would do that. Right now I would gladly participate in a trial if one became available that I qualify for. But it may take years before people with mild hearing loss and mild tinnitus can participate in any clinical trials. They usually target people with severe to profound hearing loss.

 

What's there to be ashamed of? Women's tee clubs can be fun!

Don't feel bad for us! We don't need no pity.