Inner Ear Hair Cell Regeneration — Maybe We Can Know More

why do i feel like i have this eh

 

It's only an abstract (paper provisionally accepted) with the paper to follow out of Huawei Li's lab: https://www.frontiersin.org/articles/10.3389/fnmol.2017.00426/abstract
It's basic science - and only an abstract - but it looks like a second way to activate the Lgr5+ progenitors. I believe Li was a member of Heller's lab when Heller was at Harvard and has done quite a bit of interesting work in the last several years.

 

Action on hearing loss year end report.

 

Looks very interesting. I had to google sonic hedgehog gene to make sure that wasn't a typo. They really named it that!

 

It seems like everyone is moving towards the same goal: hair cells regeneration through restoration pathways-stimulating proteins and small molecules.

 

What do you guys think about CGF166 - Genvec? Can't find much about it here. Are they already in trial?

 

They are in a phase1/phase2 trial. It won't complete until 2019 at least. Tack on a couple years after that at least to get to market. Below is the latest I have.

https://www.hearinglossjournal.com/cgf166-latest-news/

 

How Can they say people with Such severe hearing loss create new hair cells? I thought it was impossible due to lack of prognitor cells? Read some people show improvements. Too bad u can't find the results of the tests on monkeys. Hope one of the things going in trials will work for us

 

Apparently it's a problem with stem cell technology, because cancer cells like to use stem cells too.

Same thing with antioxidants -- overall, they seem to prevent cancer, but as soon you have some kind of tumorous growth, it can harness antioxidants to accelerate growth.

So the technology around using stem cells, or anything that "makes cells proliferate" (which is what Frequency plans on doing) has to be very, very precise. It needs a mechanism to either only work in the area it's meant to be in. Similar issue with CRISPR technology. Here's an interesting podcast about CRISPR as a primer: https://www.samharris.org/podcast/item/humanity-2.0

Might be better to 3D print a cochlea and just replace lol.

 

Yeah, I think the average time for a drug/treatment to go to market is 10 to 15 years, and that's only if it's really successful.

Hopefully, as the tech industry gurus start to age, they start pouring some resources into these fields to accelerate the process -- Google already has "life extension" research they've been doing for a long time now. Although, the problem there is that the tech crowd doesn't interface neatly with biology fields -- the difference being essentially "we invented coding and computers, we didn't invent genetics and our bodies".

 

From my perspective, the science has passed CGF166 by - particularly since administration is terribly invasive. Yes, as already noted, there is a Phase 1/2 trial.

See this paper among others: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573859/ CGF166 directly increases ATOH1 which causes supporting cells to transdifferentiate into hair cells. Audion and Frequency indirectly increase ATOH1 via inhibition of the Notch signaling pathway. Of course Frequency is attempting to go a step further and induce division in supporting cells.

Based on what I have seen so far, I am not worried about cancer in Frequency's approach. It is fundamentally different than what most people think of as a stem cell treatment. First, it is targeted to the inner ear only. Second, it will only affect a subset of cells in the inner ear, and finally, if it works as advertised it is restarting a natural process which, if successful will have a natural "off switch". None of this guarantees success - and there are reasons to be *very* cautious - but it is fundamentally different than an injection of stem cells.

Assuming the Phase 1/2 trial is successful and that for some reason there isn't a Phase 3 trial.

 

Very good points -- I can imagine it's easier to target the "supporting cells" and say "make a few copies of yourselves and then develop into hairs". It's not shooting young stem cells into there and hoping for the best, lol.

The trick will be ensuring a process that lets you maintain more supporting cells than hair cells, because then the process can be repeated. You could imagine people getting the procedure done a handful of times in middle age through to senior years.

 

The last I heard is: "The results so far are promising. 'There have been a couple patients with hearing improvement, so we are definitely encouraged.'"

Source: https://www.hearinglossjournal.com/cgf166-latest-news/

If the reporting is accurate, that's definitely strong proof of concept.

 

Invasive -- my friend, I want a full y 3D printed bionic ear that uses a strong material for sensor in place of crummy hair cells that are susceptible to viruses and noise and what not. ;-)

Cut me open and INSERT!

 

The frustrating thing is the pace of the trials. They have to restrict the acceptance criteria so much because there is so much variability in what causes the hearing loss and who you accept could impact the outcome of the trial depending on what caused the hearing loss (genetic disorder, etc.). You have to try to control as many variables as possible, but still find enough people to complete the trial. Frequency only has one enrolled so far and they need to be patients who are getting cochlear implants. I get this, they are trying to test the drug delivery method and find out how much of the drug diffuses through the round window. Setting them up for a Phase 2. I'm not sure what is going on with Audion and the REGAIN Trial. Their website says they still aren't recruiting. CGF166 is another example because it is something new, they have to really restrict who gets the drug initially.

 

I suspect -- although no one would say this -- Frequency also needs patients who are profoundly deaf because they have "less to lose". If something goes terribly amiss, and you had a healthy patient lose hearing, that would be rough, and potentially opens up the door for liability (even with all the paperwork and waivers and NDAs I'm sure they have, I'm sure that's part of the thinking at least from their legal team's perspective).

So, to the one person who is participating in Frequency's trials, and the others participating in various trials like CGF166, I truly salute you! These people are the astronauts of our time.

 

@parsky. How do you know that Frequency has only one patient enrolled? Do they have a counter at their site? What I do not understand is that FX did not include an effectiveness test parallel to their current delivery test. It would speed up things instead of this serial approach.

 

Out of curiosity, does anyone know if there is any research that contradicts the established notion that once hair cells are damaged, they can't grow back on their own.

The reason I'm asking is, it seems I've noticed a few surprising findings about how well our body regenerates (our lungs, for example), and so I'm curious of there's anything out there that suggests the problem is more complex (perhaps, for example, hair cells regenerate at incredibly slow rates, more like how we replenish neurons very, very slowly).

Anyone got anything?

 

Yeah, I thought this, too. But if CGF166 end up being successful, can't they simply look for another less invasive delivery method (something like Frequency's or Audion's)?

 

No, I don't think so. It's a different approach. If you look at genvec's web page there is significant discussion of there gene delivery approach. Even if possible, it would likely require additional trials showing it is effective without adverse events using a completely different delivery system.

Moreover, there is nothing special about frequency's or audion's approach so presumably if genvec could have used something significantly less invasive, they would have.

 

one of the trial registry pages indicates that there is one enrollee. However it is unlikely that page is updated in real time.

There is no scope for effectiveness given that participants are receiving cochlear implants. For that there would need to be some time between injection and the testing which doesn't work with the CIs. I am thinking of this as a pre-clinical trial in humans.

 

It wouldn't surprise me! I mean for a long time it was "known" that the brain was impossible to repair.

I would also like to say that I like the words from the guy that acceptance is the most important thing. Sure there will more likely be a cure in the future but your own death will always be closer. And it could be that we all die in a nuclear war one day.

 

You would need to define the exact parameters of damage. So one could contrast the difference between cellular stress and cellular damage something many confuse, for instance if you press your finger with the force of your body weight on a table for an hour it is very likely that you have damaged cells (blood, nerves etc) resulting in a lesion, but press it in the same way and this time take regular breaks every so often and one could arguably continue this; injury free, for an indefinite length of time. Also, if someone regained their hearing after sudden hearing loss they may never report it, so there could well be a trove of such cases that have never been seen in clinic. Damage to the balance organ is also considered irreversible, here 3 famous vestibular scientists ponder this bizarre case of recovery. password: ttalk https://www.docdroid.net/S1LjNHz/ob...-superior-vestibular-neuritis-manzari2011.pdf As the parameters of balance function amongst normal community dwelling adults is well known and can be quickly measured, it is not so with hearing, one could already have deteriorated hearing pre injury and this could obfuscate conclusions of hearing test results post injury in the event of even a slight recovery (perceived recovery maybe I should say)

Just to keep the thread topic under focus here are some review papers
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534485/

http://docdro.id/TWuxw7g
pass: ttalk


Moderators: Please keep the journal subscription articles on external docdroid servers so they are not stored on tinnitustalk servers.

 

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372587

 

This is a very, very good point. The literature only (or largely) reflects what can be observed in either a lab setting, or reports from people who appear to have lost their hearing permanently.

But that's one of the things I'd want to discover, were I a researcher -- is there a natural regeneration process that is already going on that we can harness. I suppose they are doing that by turning to other animals (chickens keep popping up in my reading) and seeing if we can apply that to our own hearing, but I wonder if anyone has really deeply looked at any of our own natural abilities.

I suppose they have done that a little with antioxidants. But if regeneration is already happening, but at very long timescales, I wonder if there's a way to accelerate that (so for example, there are supplements that accelerate neurogenesis in the case of neurons).

 

after my last episode with hearing loss, i really have high hopes for frequency treatment (which is probably a bad thing)

 

asked Will some questions

 

Sounds great to me. He sounds confident. From which company is he?

 

Frequency Therapeutics i think

 

Hope You're right. Lets first see how audion's working. They test on human whit not severe hearing loss, So i think we can expect some effect more at audion's first trial then frequency's. If any. Or am I wrong?