Inner Ear Hair Cell Regeneration — Maybe We Can Know More

You don't even take the time to read this thread jd. If you want your hearing loss cure so much, why not ?

Frequency TX are starting a clinical trial within 18 months they say. We don't know what will happen next : I guess it will be at least 8 more years to reach the market if everything goes well. But not a lot of clinical trials succeed.

 

I believe things will speed up in the next years. I talked to a Scientist from the hearing research centre Tübingen in Germany on friday and he told me that his company will do human trials with regenerative inner ear medicine this summer and the corresponding medicament will be released soon after.
I know this isn't much information but I can see the following: There is a completely open market which promises billions of profit. There are enough signs that the regeneration of the inner ear will work. There is a dozen of companies which pursue to develop a treatment and yet you can't get much information about their work. For me this are signs that they are on the race to be the first one on the market.
My bet: 5 years for the first and 10 years for a groundbreaking treatment.

 

Which company?

 

The reality is that around 10 or 15 % of clinical trials are completed and give access to the market.

Frequency TX seems to be the more advanced for now...

You have to tell us more about this German scientist. If something is tested this summer in Germany, many of us could apply.

 

I didn't ask him for the name of the company, because I was there for a medicinal examination and time with him was short. I thought that the company can be found by searching for his name. Unfortunately I had no luck, now I regret not asking him. I will ask him, the next time I am there. His name is Dr. Stefan Wolpert. Maybe another one can find his company or the trial.

 

Could be this company: http://audiocure.de/

They seem to be focusing on acute hearing loss.

 

I would love if the first treatment came in Germany

 

What connexion did you find between Stefan Wolpert and them ?

 

No connection, it could be something different.

 

Guys, regarding Frequency's clinic trial I think the bar for success is so low that unless its a complete failure their will be a hearing "cure" possible in under 5 years. But remember that "success" could just mean an average 55-75 dB hearing threshold over maybe 1-2Khz (with improved frequencies somewhat random). Unfortunately with this "success" I could easily see Frequency and their investors throwing in the towel because they didn't hit a home run. So a "cure" should be possible in under 5 years but not available.

 

If there only was proof of concept to start with.

 

For sure there would be some other firms and labs willing to keep up the research. The paper they published two/three weeks ago was totally groundbreaking and could lead to something even greater. That's how science works.

 

So its NOT a cure for ears, but they are on the "Brink" of a cure for blindness, then everyone can focus on ears next. The eye and the ear may also be innervated as people with vertigo experience nystagmus (an inner ear disorder causing vision problems). So perhaps and ear cure is not too different from the cells used cure blindness.

http://www.express.co.uk/news/science/753001/cure-for-blindness-restore-sight-riken-centre

 

I have a question guys, when they talk about regenerating the hair cells within our ears and using supporting cells, does this mean that the old dead hair cells will remain? From what i am aware they want to use "progenitor supporting cells (frequency TX) " but this hints at regenerating hair cells next to dead ones from what i'm lead to believe.

Wouldn't this mean that tinnitus and H wouldn't go because the dead ones still remain despite there being new ones in the supporting cells? What about repairing our broken ones? I saw something on the sea anemone but this is YEARS off. If someone could clarify that'd help!

 

It's likely that dead hair cells themselves are not responsible for T and H. It's the synapses that were attached to them. Once a hair cell dies, the synapses start to retract.

I assume dead hair cells disappear, the body eliminates them.

 

I don't think that dead tissue will remain.
Could this mechanism be at work in our inner ears after hair cell damage/death?
https://www.quora.com/How-do-our-bodies-dispose-of-dead-internal-cells

 

But who knows about zombie tissue?

In fact we all know the pics from electron microscopy showing the crippled IHCs. So they are not removed.

 

Here's a video of Frequency's founder at TED talking about their treatment (I don't know if it has already been posted, but just in case):

What if our body’s dormant stem cells...

Remember that Frequency's holding a presentation at Cowen & Company 37th Annual Healthcare Conference today (http://www.frequencytx.com/news-events/news-events-press-release-03-01-2017.php). Maybe we'll get some new info.

 

If they are not removed then they are still alive?

 

I believe the presented yesterday (Wednesday). I would not expect any new information (and so far there isn't a press release about anything new).

 

You're absolutely right. I thought 08/03 was today

The video was uploaded yesterday, so at least my message wasn't a total failure

 

About GenVec:
https://www.bloomberg.com/news/arti...els-gene-therapy-to-help-reverse-hearing-loss

"Swiss pharma giant Novartis AG is working with GenVec to use gene therapy to stimulate the growth of hair cells. A modified virus delivers a copy of a gene called Atonal 1 that tells supporting cells in the ear to convert into hair cells.

While gene therapy probably won’t help people who are born deaf, because the brain hasn’t developed to interpret sound, GenVec Chief Executive Officer Doug Swirsky says he’s hopeful it will work for patients who lost their hearing at a young age. GenVec’s product could reach the market in three to five years."

They are still recruiting participants for Phase 1/2 till August 2017.

 

This is old (Oct 2016).

Assuming they are still planning to enroll 45 patients in the Phase 1/2 trial, it is very, very (very) unlikely that they will be stopping recruiting in August. From Feb 3, 2017: "The first patient received CFG166 in 2014 and they had planned on a total of 45 patients. But so far only 11 people have undergone treatment. For Dr. Lustig and his colleagues that is a disappointingly low number. " (http://www.hearinglossjournal.com/cgf166-latest-news/#more-881) The issues are the stringent inclusion/exclusion criteria and the fact that there are only 3 locations. He discusses adding sites, but that doesn't solve the strict inclusion/exclusion criteria. I suppose it is possible that they will stop with fewer than 45 patients though that might create some issues with moving to a Phase 3 trial.

 

It's what they say at ClinicalTrial's site: https://clinicaltrials.gov/ct2/show/NCT02132130

So far, the trial's biggest concern isn't results but to find participants who fit the inclusion criteria, so I guess Phase 3 is guaranteed sooner or later.

 

I understand what the clinicaltrials.gov entry says. It isn't exactly current and is in no way a guarantee.

Since we don't know the results of Phase 1/2, there's no way of knowing whether there will be a phase 3 trial. Regardless of the outcome, much will be learned from this trial (e.g., safety or not of delivering different doses of trials directly to the inner ear). That said, based on subsequent science, I am skeptical that this will be particularly successful.

 

so my question......do the old hair cells/dead synapses remain when they regenerate the supporting cells? Or when they mean regeneration they mean regenerating in the EXACT place where the damage has occured (meaning that they still fire away causing T/H)

 

Dead hair cells would almost certainly be cleared out by the body. This is true in mice (http://link.springer.com/article/10.1007/s10162-014-0480-x) and birds (http://www.jneurosci.org/content/30/37/12545).

I'm not sure I understand what you mean. The loss of synapses in particular results in the remaining synapses firing at a higher rate in order to preserve hearing thresholds (I believe the reference is Kujawa and Liberman 2009.). If regenerated hair cells were functional and properly innervated, then that would restore missing information which, assuming the firing rates of the other synapses comes down, should in principle reduce tinnitus. (With the extra assumption that Liberman is correct that this synaptopathy is a cause of tinnitus.)

Beyond that, I'm not sure anyone knows how exactly regeneration will happen in the living cochlea (perhaps with the exception of some folks at Frequency Tx). The reason is that until recently, it was not possible to regenerate enough HCs to explore this in great depth. The dramatic increase in the number of hair cells that can be grown in the lab that is described in the recent Cell Reports paper by McLean et al is exciting, but, even assuming the resulting HCs are functional, there is still the issue of controlling the process. One of the challenges with regeneration will be to regenerate the right hair cells in the right place with the right orientation, properties, etc. For example, if someone has high frequency hearing loss, then creating hair cells tuned to low frequencies is not helpful. During development there are natural, endogenous processes to make that happen. What isn't clear from the published research is what it will take to replicate that process in the adult cochlea following some type of damage. The fact that it is now possible to generate large number of hair cells will speed the answers to these questions and a host of others.

 

Does anyone know if the Frequency trials, or any other subsequent trial will have to use the same inclusion/exclusion criteria for participants that GENVEC has used?

 

This is not yet known although we can reasonably assume that for phase 1 trial, only people with severe/profound hearing loss will be included as participants.

 

I think so. It will be interesting to see if they target mild/moderate hearing loss later.