Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Rasmus]

My understand, ing is that the prime sign of HHL is bad hearing in a noisy environment. This matches with your description. I guess you might be right, but I don't know for sure...


They did the normal audiometry with audiogram? Have they done ABR? If you have a normal audiogram they should do the ABR test. If you have synaptopathy, which is one of the first causes of HHL as described initially by Liberman et. al. they will be able to tell that. But even here, the medical establishment is lacking. New discoveries like HHL take a time to translate into clinical use and protocol.

Have you talked to them about HHL? Do they know what it is? I doubt it.

It's sad that we have to diagnose ourselves, based on the latest research. But it is what it is. I hope this will all change when the first medical treatments for hearing loss come to the clinics. They will have to change their diagnostic protocols.

No i have not told them about Hidden hearing loss but again they didt tell me something like HHL was a thing so i guess they dont know anything about it. HHL was something i learn about 3 mounth ago so something. And last time i was at a ENT were 4 mounth ago. I dont know what a ABR is they only took a hearing test and presure in my ears. And told me everything was fine :/ I have been there 2 times.
I think i have a little bit hearing loss to because when i was listing to this Beb sounds it was very hard to hear harder then back in the days when i was a child

But i have been doing some frequency test on this website myself http://www.szynalski.com/tone-generator/

And i can hear up to 15800-16000 before i cant hear it anymore and i have been told that i should be able to hear a little more in my age and im 22 and my T is a high freq sound

 

[Mricha37]

i like how people on this website are downplaying all of these amazing stem cell and gene therapy discoveries like they know more than the researchers. again, i bet we dont even know half of what goes on behind closed doors. Harvard announces two major discoveries just a few weeks apart. we have momentum, they are hopefully going to start on larger mammals soon then human trials!!!!

 

[Samir]

No i have not told them about Hidden hearing loss but again they didt tell me something like HHL was a thing so i guess they dont know anything about it. HHL was something i learn about 3 mounth ago so something. And last time i was at a ENT were 4 mounth ago.

You can ask them about HHL on your next visit. See how they react! Patient smarter than the doctor!

I dont know what a ABR is they only took a hearing test and presure in my ears.

ABR stands for Auditory Brain Response. It's a special kind of test that helps determine hearing loss type and detect auditory nerve and brainstem lesion. See if you find the videos below useful.

This video shows an example of a combined OAE and ABR tester:


This video demonstrates how the test is done on a baby:


What you describe sounds like they just did the regular pure tone audiometry and tympanometry.

i can hear up to 15800-16000

That's quite impressive! I don't know if 15000 Hz is normal for your age group. Most people can't hear above 13000 Hz, myself included.

 

[Rasmus]

You can ask them about HHL on your next visit. See how they react! Patient smarter than the doctor!


ABR stands for Auditory Brain Response. It's a special kind of test that helps determine hearing loss type and detect auditory nerve and brainstem lesion. See if you find the videos below useful.

This video shows an example of a combined OAE and ABR tester:


This video demonstrates how the test is done on a baby:


What you describe sounds like they just did the regular pure tone audiometry and tympanometry.


That's quite impressive! I don't know if 15000 Hz is normal for your age group. Most people can't hear above 13000 Hz, myself included.

Thanks for sharing this i will take a look at it !, but back in the days i had no problem at all hearing in noise envoiment, i could easy hear when people was talking and listing to tv at the same time, i could simple choose what to focus on the TV or the other people talking in the same room. But now i cant do that, everyone just sounds bla bla bla i can pick some words out here and there but i cant follow the full convensation :/

 

[Samir]

i like how people on this website are downplaying all of these amazing stem cell and gene therapy discoveries like they know more than the researchers.

If you're referring to me, I am mainly angry with the audiologists and ENT doctors, not with the biologists, geneticists and neuroscientists that do the research. Researchers are the only ones working on cures. One way to look at it is that they are the only ones that care for us and want to help us, but they are not medical doctors so they can't help us directly.

I am also cautious about the implications for tinnitus when hearing loss is restored. I know everyone expects this to cure tinnitus along with the hearing loss. I am a bit skeptical about this. But I hope they prove me wrong one day. We shall see. It's not too far off now.

Harvard announces two major discoveries just a few weeks apart.

Just for the record, which ones are you referring to?

 

[Ian Mac]

Unfortunately tinnitus is not even a real thing - there are noises that come from spine injuries there's noises that come from ear injuries there a noises that come from brain injuries there's noises that come from cochlear hydrops and menieres desease and perelymph fistulas and superior canal dehiscence and the most underrecognized of all poor ion balance - but none of these noises should ever be called tinnitus because it's so vague we'll never know more we can never no more if we keep calling each different type just plain tinnitus and we'll never know more. I urge you to find out where your tinnitus is actually coming from instead of just pretending that your hair cells are damage from that music because that's probably not the case.

 

[spingee]

For example i was born with normal hearing, due to infection or antibiotics in child hood and loud music exposure torough my life i have now mild to moderate loss in both ears. So ive lost lot of hair cell and i have no tinnitus.

 

[Rasmus]

Unfortunately tinnitus is not even a real thing - there are noises that come from spine injuries there's noises that come from ear injuries there a noises that come from brain injuries there's noises that come from cochlear hydrops and menieres desease and perelymph fistulas and superior canal dehiscence and the most underrecognized of all poor ion balance - but none of these noises should ever be called tinnitus because it's so vague we'll never know more we can never no more if we keep calling each different type just plain tinnitus and we'll never know more. I urge you to find out where your tinnitus is actually coming from instead of just pretending that your hair cells are damage from that music because that's probably not the case.

Tinnitus means you can hear a sound that other people cant hear, when there is no sound around you.

 

[Reinier]

we have momentum,

I am curious to see if these press releases from Harvard are making other researchers/companies inclined to also release discoveries they where keeping under wraps.
I know, wishful thinking?? But how knows?

 

[Sizzle]

I was just listening to Science Friday on NPR and I'm very excited!
http://www.sciencefriday.com/segments/can-this-treatment-combat-hearing-loss/

Human trials will likely begin within the next two years or sooner! (18 months he said!)
Now, if they could only regrow the hair on my head so easily...

 

[Foncky]

"Karp hopes that one day there will be a treatment to restore hearing loss with just one outpatient visit."

"Mmh, I don't hear well these days. Let's go to the ENT... Mmh, much better !"

 

[Sizzle]

Clearly there are clinically promising treatments being trialed for hearing loss due to damaged progenitor hairs cells in the cochlea- but just two weeks ago my so called, "ENT Specialist" said,

"Go home, lick your wounds, cry a little, then get used to it. There is no cure or treatment. "

Then he yelled out into the hall, "Next!"

Really? Not a single, hopeful word about cutting edge hearing restoration research? What's up with that? Guess he didn't want to give false hope, but he left me feeling completely, utterly hopeless and depressed.

I feel better now - at least I know there are people out there making progress toward a possible treatment for some of us.

 

[Foncky]

Your Ent is a bad doctor obviously. He has no clue. And a bad person.

 

[Rasmus]

Clearly there are clinically promising treatments being trialed for hearing loss due to damaged progenitor hairs cells in the cochlea- but just two weeks ago my so called, "ENT Specialist" said,

"Go home, lick your wounds, cry a little, then get used to it. There is no cure or treatment. "

Then he yelled out into the hall, "Next!"

Really? Not a single, hopeful word about cutting edge hearing restoration research? What's up with that? Guess he didn't want to give false hope, but he left me feeling completely, utterly hopeless and depressed.

I feel better now - at least I know there are people out there making progress toward a possible treatment for some of us.

Well a guy like that is not a good person.

 

[Rob111]

I came across this Youtube clip on the Hough Institute and found it to be positive and encouraging.

 

[Sizzle]

http://www.frequencytx.com/

I do hope this is the real deal...

 

[Reinier]

The Hough Ear institute clip almost makes you think the cure is already there. Waiting for the first clinical trials. Very optimistic.

http://houghear.org/new-tour-dates-for-2017/
Quote: "Did you know we are on the verge of curing deafness? Our researchers are using silencing RNA, nanoparticle delivery systems and antioxidant technologies to reprogram, heal and protect cells in the inner ear. We want to give you the opportunity to hear our researchers explain these technologies and look through our microscopes and see the results for yourself."

Unfortunately it is in America. I would have liked this. If it is for "the general public" that is.
I suppose this is primarily to raise money for research.

 

[Aaron123]

The Hough Ear institute clip almost makes you think the cure is already there. Waiting for the first clinical trials. Very optimistic.

Yeah, they have been very optimistic for some years now with little in the way of publications (or other concrete evidence) to show for it. The most recent publication listed on their web site is from 2013, and the most recent paper on siRNA is from 2012: https://www.ncbi.nlm.nih.gov/pubmed/23850665 That paper has only been cited 11 times since publication. The senior author on that paper has published a few papers since then, mostly on blast injury work done for the military. My cynical sense is that they did a lot of grant work for the military and grant funding has dried up. As always, I hope they have something just around the corner, but there is no evidence of it.

 

[bill 112]

Yeah, they have been very optimistic for some years now with little in the way of publications (or other concrete evidence) to show for it. The most recent publication listed on their web site is from 2013, and the most recent paper on siRNA is from 2012: https://www.ncbi.nlm.nih.gov/pubmed/23850665 That paper has only been cited 11 times since publication. The senior author on that paper has published a few papers since then, mostly on blast injury work done for the military. My cynical sense is that they did a lot of grant work for the military and grant funding has dried up. As always, I hope they have something just around the corner, but there is no evidence of it.

What does citing a paper mean Aaron? It's just something I've always wondered about, is it a good or bad thing to cite a paper?

 

[SilverSpiral]

What does citing a paper mean Aaron? It's just something I've always wondered about, is it a good or bad thing to cite a paper?

I think he is implying that the paper only being cited 11 times could be an indication that there is not much "activity" going on in the research? Because he later mentions that he suspects their funding may be gone. To me that is a fairly big, but interesting assumption to make, but I don't know that much about how stuff like that works. And have never thought about it that way. If I did, I would be more likely to assume that they may not be publishing much concrete data on their research to prevent their "cure" from being taken over by other companies? Or if it is primarily military funded research like Aaron suggests, they could have some red tape around their research because of that? Who knows.

 

[Aaron123]

What does citing a paper mean Aaron? It's just something I've always wondered about, is it a good or bad thing to cite a paper?

Citations are a good thing. At the end of published papers (or unpublished papers though those are rare in medicine), there will be a list of references. Each time a paper appears in a list of references counts as 1 citation. Obviously the number of citations will vary to some degree with how long a paper has been published, but given two papers were published at approximately the same time, the paper with more citations is likely to be the more important paper as judged by whether other scientists think it is interesting/good enough to reference in later work.

There are a couple of caveats to this: 1) some people like to cite their own previous work so that can/should be discounted. What should matter is whether other people think what you did is interesting. 2) It is also worth paying attention to the journals where the paper is being cited. Citations in top journals such as Nature are more meaningful than citations by papers in some journal no one has heard of.

Similarly, when papers are published, you should pay attention to the journal. Generally speaking, a journals like Nature, Cell, or Neuron will publish very top stuff and then there is an ordering below that. It ranges all the way down to journals where you basically pay a few thousand dollars and they will publish whatever you send. There may be some nominal "peer review", but they are essentially pay to publish. Thus all published papers are not equal even if they are all "peer reviewed".

In this case, I went to the Hough Ear Institute web site, and clicked on their research publications link: http://houghear.org/publications/ The second paper is on siRNAs and was published on March 27, 2012. (According to pubmed, it actually looks like it was published in July.) I am assuming that this is their most recent work on this topic, but that isn't really clear because their publications just stop on Nov. 1, 2013 which either means they haven't published since then or they no longer update this information (which seems bad to me if you want people to give you money).

Since their link to the paper on their web site is broken, I googled the title of the paper and got this https://www.google.com/search?q=Reg.../Hes5+modulation+with+siRNA&ie=utf-8&oe=utf-8 The first link is a link to the paper. But don't click on it. Instead, look at the third line that starts "by X Du..." also says "cited by" and at the moment it has been cited by 11 other papers. If you click on the "cited by" link, it will show you the papers in Google Scholar that have cited this one.

For comparison, we can take another paper published a few months before the Du et al. paper - Mizutari et al 2013 with Albert Edge as the senior author. This was published in January in Neuron and has 153 citations: https://www.google.com/search?q=Not...ring+after+acoustic+trauma.&ie=utf-8&oe=utf-8 If you look at the citations, they are also of much higher quality. So this paper is much more important than the one on siRNAs from the folks at Hough.

(I'm not intending with any of this to disparage the folks at Hough and what they are doing. However, if you are suggesting, as they are, that you are close to the cure ("Did you know we are on the verge of curing deafness?"), it would be nice if there were some published evidence of this.)

 

[Aaron123]

Because he later mentions that he suspects their funding may be gone.

It's not that I suspect it; it's that they say it. From their page on grants awarded (http://houghear.org/grants/): "85% Reduction in Government Grants
We are experiencing a major paradigm shift in our revenue and expense model. We're planning on an 85% reduction in grants available for research from the federal government. As a result, we're now seeking grants from private foundations, companies, and private donors to support critical research."

If you look at the grants awarded, you will see many of them are from the military - the U.S. Navy in particular.

Additionally, while Federal funding is down, I don't believe it is down 85% so for some reason, Hough has taken a larger hit than others.

Or if it is primarily military funded research like Aaron suggests, they could have some red tape around their research because of that?

The military - or Federal Government in general - is unlikely to put "red tape" around medical discoveries. Weapons would be a different story.

I would be more likely to assume that they may not be publishing much concrete data on their research to prevent their "cure" from being taken over by other companies?

There may be some truth to this, but it is hard to square that with the recent paper published with a number of Frequency Therapeutics co-authors or the fact that Decibel Therapeutics recently presented some of their work at the midwinter ARO conference.

 

[Mricha37]

Y'all do realize that freqxt is not a university that would normally do alot of publications. Truth is, they are out to make money. Go find a for-profit company willing to give out trade secrets lol!

 

[foryourinfo]

Y'all do realize that freqxt is not a university that would normally do alot of publications. Truth is, they are out to make money. Go find a for-profit company willing to give out trade secrets lol!

You do realize that inner ear otology pharma companies typically do not have in-house research, right?

 

[Mricha37]

You do realize that inner ear otology pharma companies typically do not have in-house research, right?

You do realize you're a douche bag, right?

 

[SilverSpiral]

It's not that I suspect it; it's that they say it. From their page on grants awarded (http://houghear.org/grants/): "85% Reduction in Government Grants
We are experiencing a major paradigm shift in our revenue and expense model. We're planning on an 85% reduction in grants available for research from the federal government. As a result, we're now seeking grants from private foundations, companies, and private donors to support critical research."

If you look at the grants awarded, you will see many of them are from the military - the U.S. Navy in particular.

Additionally, while Federal funding is down, I don't believe it is down 85% so for some reason, Hough has taken a larger hit than others.


The military - or Federal Government in general - is unlikely to put "red tape" around medical discoveries. Weapons would be a different story.


There may be some truth to this, but it is hard to square that with the recent paper published with a number of Frequency Therapeutics co-authors or the fact that Decibel Therapeutics recently presented some of their work at the midwinter ARO conference.

Wow you really research this stuff about the companies well. I just glance at articles to see if anybody has testing open to the public because im desperate for a cure. The only thing I'd note is that you saying the military/federal government in general is unlikely to put "red tape" around medical discoveries. I could think of several situations where they would. Especially where medical discoveries and weapons overlap, which may be the case sometimes with modern technologies, without even going into "conspiracy theory" territories.

 

[Samir]

What is the window of opportunity

I just want to add that the window of opportunity varies by the exact type of damage and the extent of the damage. Many of us with noise induced hearing loss (NIHL) are said to have sensorineural hearing loss (SNHL). But this diagnose doesn't say if it's sensory or neural loss. This compound word sensorineural is used instead.

There can also be a mix of both, a little bit of sensory and a bit of neural damage. This is not to be confused with "mixed hearing loss" which describes a combination of middle ear damage (conductive hearin gloss or CHL) and inner ear damage (SNHL).

In case of non-genetic, noise induced or ototoxin induced neural damage, the window of opportunity can stretch to several years, if not decades. From a therapeutic standpoint, Liberman et. al. has shown that survival of neural connections is more important than hair cell survival. Neural degeneration is called synaptopathy or neropathy depending on the stage of degeneration.



The most important component in neural survival and outlook for future treatment is the survival of spiral ganglion neurons (SGN) which make up the cell bodies that connect to the hair cells. These can survive for several years. I have seen numbers like 10 years or even 15 years mentioned. I can't back this up. But it's evident by the people who have severe or profound hearing loss and get a cochlear implant several years after onset of hearing damage, and they get a great increase in hearing thresholds. This would not be possible without survival of nerves.

So unless the hearing loss is caused by a genetic defect, the window of opportunity should be several years if not decades, so the outlooks for a successful treatment should be very good. They just need to make these therapies available. As always, the sooner you treat a condition the better the results are.

 

[Samir]

So ive lost lot of hair cell and i have no tinnitus.

You don't have tinnitus or your tinnitus subsided? I haven't met anyone here that does not have tinnitus at all.

I was just listening to Science Friday on NPR and I'm very excited!

Using a new technique, Jeffrey Karp and his team at Brigham and Women's Hospital were able to stimulate and grow 2,000 times more hair cells than has previously been possible.

By a factor of 2000? So if they previously could grow 200 cells, they now can grow 400000 cells? That's crazy! That's 13 times more cells then there are in both human ears! This doesn't make sense. Because this has already been reported, this is part of the Frequency's latest press release. The factor is 60, not 2000. With a factor of 60 that's 12000 cells.

Furthermore, the team achieved 60-fold enhancement of hair cell production from the progenitor cells compared to current methods.

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

The factor 2000 relates to supporting cells!

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.

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

 

[Samir]

Y'all do realize that freqxt is not a university that would normally do alot of publications. Truth is, they are out to make money. Go find a for-profit company willing to give out trade secrets lol!

What kind of secrets would that be? If their products are based around existing and publicly accessible research results from research done at university, wouldn't that mean that we already know their secrets? Or at least have an idea of what that might be?

It would seem to me that their best protection against being ripped off by another company is not secrecy itself but making sure their methods are patented.

 

[jdjd09]

Any new hope in the world that there will be a cure to hearing loss in the next 5 to 10 years? Any company claiming they will have one in that timeframe or less for a hearing loss cure (or treatment to bring back most of ones hearing)?