Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Reinier]

There are two reasons I believe "louder tinnitus" could actually mean less damage.

I hope you are correct. My tinnitus is getting louder .

Nick for all of us once the treatment to reconnect the neurons is available it will be too late if the window is one year.

This is the reason why I think the approach of (amongst others) Action On Hearing Loss, Hearing Health Foundation and Stanford is hopeful.
They look at ways to regenerate what is lost. In order to do that they need to understand how the inner ear develops.
Not easy, but they know a lot already.

 

[Mario martz]

Nothing New
http://wtnh.com/2016/08/02/your-teenager-could-be-at-risk-of-a-common-hearing-problem/

still audiologist dont know any shit

 

[Nick Pyzik]

I hope you are correct. My tinnitus is getting louder .

This is the reason why I think the approach of (amongst others) Action On Hearing Loss, Hearing Health Foundation and Stanford is hopeful.
They look at ways to regenerate what is lost. In order to do that they need to understand how the inner ear develops.
Not easy, but they know a lot already.

You're right Reinier. I was talking with @Mario martz the other day and he explained to me that a lot of growth has happened lately. There are plenty of corporations/foundations out there researching their butts off. Time is the question.

My friend @Sasja linked me to this last night: http://hsci.harvard.edu/hearing-loss-0

It's the University of Harvard's "Stem Cell Institute" page on hearing loss. They have a focus on the sensory hair cells in what's explained throughout the page, but what they talk about in the last paragraph/section is very informative. They incorporated talk about stem cell derived-auditory neurons and what happened when they were transplanted into deaf animals.

 

[Nick Pyzik]

Nothing New
http://wtnh.com/2016/08/02/your-teenager-could-be-at-risk-of-a-common-hearing-problem/

still audiologist dont know any shit

They are literally restating the same information that has been posted about hearing risks in young adults in other recent articles. Plus, they're not correct at all about the sensory hair cell damage. Especially with the new studies that have been released regarding tinnitus, hidden hearing loss, changed speech perception in noise, and the spiral ganglion neurons/nerve fibers.

 

[Mario martz]

They are literally restating the same information that has been posted about hearing risks in young adults in other recent articles. Plus, they're not correct at all about the sensory hair cell damage. Especially with the new studies that have been released regarding tinnitus, hidden hearing loss, changed speech perception in noise, and the spiral ganglion neurons/nerve fibers.

The only good thing they did was naming or taking in consideration the recents studies in brazil.
and thats it.
fu"·$%& morons!
hahaha

 

[tomytl]

I would like to know what's up with the research coming from the Hough Ear Institue in Oklahoma. They do research for years and maybe they have something very interesting on the start. Otologicpharma licensed an approach of hair cell regeneration.
Richard Kopke, Director of Hough Ear is also founder of Otologicpharma, and this company buyed licenses for a hearing regeneration programm from Hough Ear Institute.
Otologicpharma works together with Accelebio. So there is a network behind.
I'm just not sure how advanced they are.
Does someone has more info?

http://accelebio.com/otologic-pharm...tion-technology-from-the-hough-ear-institute/

http://houghear.org/

 

[Foncky]

Guys, you're making great statements, it's all very interesting, but don't forget these statements are not scientifically proven. We can't come to such conclusions without a deep knowledge of what's going on in the labs.

For instance, I don't believe a loud T equals to an "ok" damage. My T is 12 years old and it's been louder and louder and LOUDER over the years. I can tell you it only means more damage, as I went through several acoustic traumas.

 

[tomytl]

Guys, you're making great statements, it's all very interesting, but don't forget these statements are not scientifically proven. We can't come to such conclusions without a deep knowledge of what's going on in the labs.

For instance, I don't believe a loud T equals to an "ok" damage. My T is 12 years old and it's been louder and louder and LOUDER over the years. I can tell you it only means more damage, as I went through several acoustic traumas.

Hi,
yes, ofcourse it's all speculation. Nobody knows for sure if there is a really hearing enhancing regenerative
solution in reach. So the Atoh1 Genvec Trial will give some answers. If there is a reproducable
way to regain some hearing, the future looks bright.
I would be happy if there would be some repair function in a therapeutic value of 20-30%
I do not need a child hearing, just some repair, some more sensitivity and less tinnitus.

As someone who is following this research since 2003, I can say the developments in hair cell research
are really huge. In 2003 there was almost no information about... Just a few from Otogene (today Soundpharma)

 

[Reinier]

wtnh.com/2016/08/02/your-teenager-could-be-at-risk-of-a-common-hearing-problem/
Quote: "they found the prevalence of tinnitus was 28%- which is pretty high."
Also from the same article: "It's a fairly low prevalence at the moment but unfortunately I do expect that to increase due to the noise exposure that kids today are being exposed to."
End quote.
I think 28% is a very high prevalence. We are talking about young people between 11 and 17 years of age!
Not middle aged or older.
We have seen these reports so many times. I suppose like in commercials, repeating is good for awareness.
And I can not understand what is said here: "They allow us to substitute another sound, a more pleasant sound. Hopefully in a sound the patient can control for their tinnitus in hopes that it can mask that tinnitus and make it less noticeable."
I assume masking is what they are talking about.

 

[Reinier]

They incorporated talk about stem cell derived-auditory neurons and what happened when they were transplanted into deaf animals.

Exactly my point. This is what I like to read about (and understand to the best of my ability). Stem cells contain DNA and RNA. Here we find all the information that is needed to regenerate.

Hence the possibility to build the first rudimentary inner ear in a Petri dish. I have no idea how basic this Petri dish inner ear was (does it already include SGN?), but the fact a start has been made to grow an inner ear from stem cells makes me hopeful.
It al sounds simple, but oh boy it is so complicated!
The more you learn, the more you realize how little you know…

Time heals all wounds is related to grief. But in this concept, I hope it also relates to regenerating damaged parts of the (inner) ear

 

[tomytl]

This sounds like a good tool

http://www.mononbioventures.com/

http://www.insideindianabusiness.com/story/31891694/hoosier-made-ear-in-a-dish-making-waves

 

[Aaron123]

This sounds like a good tool

There's discussion of the ear in a dish starting with this post:

https://www.tinnitustalk.com/threads/inner-ear-hair-cell-regeneration-—-maybe-we-can-know-more.3131/page-44#post-184321

 

[Nick Pyzik]

Exactly my point. This is what I like to read about (and understand to the best of my ability). Stem cells contain DNA and RNA. Here we find all the information that is needed to regenerate.

Hence the possibility to build the first rudimentary inner ear in a Petri dish. I have no idea how basic this Petri dish inner ear was (does it already include SGN?), but the fact a start has been made to grow an inner ear from stem cells makes me hopeful.
It al sounds simple, but oh boy it is so complicated!
The more you learn, the more you realize how little you know…

Time heals all wounds is related to grief. But in this concept, I hope it also relates to regenerating damaged parts of the (inner) ear

But remember, there is proof that hearing loss doesn't just mean sensory hair cell death. Or sensory hair cell death at all. In fact, I believe spiral ganglion neuronal/nerve fiber damage trumps sensory hair cell damage. We will see though as new studies come out.

 

[tomytl]

Some new findings from Sea Anemone
http://www.dailymail.co.uk/sciencetech/article-3722702/Hearing-damage-restored-sea-anemones.html

 

[Reinier]

When did it go wrong for mammals

 

[Mario martz]

When did it go wrong for mammals

Lol, stupid evolution

 

[bill 112]

Evolution isn't at fault we are.It gave us great precise hearing but it was us who decided to abuse it with noise and drugs it couldn't possibly withstand.

 

[Mario martz]

Evolution isn't at fault we are.It gave us great precise hearing but it was us who decided to abuse it with noise and drugs it couldn't possibly withstand.

I Agree with you.
too bad, some people never get to experience this problem no matter how much exposure they have.
if this was super common, some of us would have know about the dangers of noise.
and we probably wouldnt be here.

hoping big time on kyoto university

 

[Aaron123]

A cautionary tale regarding NT3 and synaptopathy: http://www.nature.com/articles/mtm201652

They used a viral vector to induce overexpression of NT3 (I believe similar to what Genvec is doing) in normal hearing guinea pigs. Results were increased hearing thresholds and issues with the nerves and connections between nerves and hair cells. For me, this highlights a couple of things: 1) The need to know the specific type of damage - assuming this result holds up, it seems like a bad idea to increase production of NT3 if there is limited or no synaptic damage; 2) The need to have very specific targets to minimize this reorganization/disorganization.

Abstract
Synaptopathy in the cochlea occurs when the connection between inner hair cells and the auditory nerve is disrupted, leading to impaired hearing and nerve degeneration. Experiments using transgenic mice have shown that overexpression of NT3 by supporting cells repairs synaptopathy caused by overstimulation. To accomplish such therapy in the clinical setting, it would be necessary to activate the neurotrophin receptor on auditory neurons by other means. Here we test the outcome of NT3 overexpression using viral-mediated gene transfer into the perilymph versus the endolymph of the normal guinea pig cochlea. We inoculated two different Ntf3 viral vectors, adenovirus (Adv) or adeno-associated virus (AAV) into the perilymph, to facilitate transgene expression in the mesothelial cells and cochlear duct epithelium, respectively. We assessed outcomes by comparing Auditory brainstem response (ABR) thresholds prior to that at baseline to thresholds at 1 and 3 weeks after inoculation, and then performed histologic evaluation of hair cells, nerve endings, and synaptic ribbons. We observed hearing threshold shifts as well as disorganization of peripheral nerve endings and disruption of synaptic connections between inner hair cells and peripheral nerve endings with both vectors. The data suggest that elevation of NT3 levels in the cochlear fluids can disrupt innervation and degrade hearing.

 

[bill 112]

@Aaron123
So the expression of NT-3 actually made their hearing worse?

Why was this exactly?I'm probably not seeing the answer even though it's right in front of me but how does re-growing synaptic nerves damage hearing?Is it because they weren't damaged in the first place and now there's a cluster of unneeded neurons throwing everything out of whack?

And how would they go about improving this?Is there anyway around it?

Sorry for the bombardment just wasn't prepared for this,all I've seen is good things so far about NT-3 so this came as something of a shock.

 

[bill 112]

I Agree with you.
too bad, some people never get to experience this problem no matter how much exposure they have.
if this was super common, some of us would have know about the dangers of noise.
and we probably wouldnt be here.

hoping big time on kyoto university

Lol I know,my mates murder their hearing day in and day out and have done so their entire lives and are absolutely fine.Me?Well I barely ever went clubbing or to concerts,3 in my entire life and look at me nowHoping for some good news,could really do with it.

 

[Reinier]

A cautionary tale regarding NT3 and synaptopathy

Although I realise there is no "magic bullet" I was disappointed after reading the document. Perhaps I was expecting NT-3 gene is the answer. Which of course is not the case in something so complex as hearing.
It was tested though on guinea pigs with healthy inner ears.
Anyway it must be a combination of processes to repair damage. Not just one protein called Neurotrophin-3.

 

[Nick Pyzik]

A cautionary tale regarding NT3 and synaptopathy: http://www.nature.com/articles/mtm201652

They used a viral vector to induce overexpression of NT3 (I believe similar to what Genvec is doing) in normal hearing guinea pigs. Results were increased hearing thresholds and issues with the nerves and connections between nerves and hair cells. For me, this highlights a couple of things: 1) The need to know the specific type of damage - assuming this result holds up, it seems like a bad idea to increase production of NT3 if there is limited or no synaptic damage; 2) The need to have very specific targets to minimize this reorganization/disorganization.

Abstract
Synaptopathy in the cochlea occurs when the connection between inner hair cells and the auditory nerve is disrupted, leading to impaired hearing and nerve degeneration. Experiments using transgenic mice have shown that overexpression of NT3 by supporting cells repairs synaptopathy caused by overstimulation. To accomplish such therapy in the clinical setting, it would be necessary to activate the neurotrophin receptor on auditory neurons by other means. Here we test the outcome of NT3 overexpression using viral-mediated gene transfer into the perilymph versus the endolymph of the normal guinea pig cochlea. We inoculated two different Ntf3 viral vectors, adenovirus (Adv) or adeno-associated virus (AAV) into the perilymph, to facilitate transgene expression in the mesothelial cells and cochlear duct epithelium, respectively. We assessed outcomes by comparing Auditory brainstem response (ABR) thresholds prior to that at baseline to thresholds at 1 and 3 weeks after inoculation, and then performed histologic evaluation of hair cells, nerve endings, and synaptic ribbons. We observed hearing threshold shifts as well as disorganization of peripheral nerve endings and disruption of synaptic connections between inner hair cells and peripheral nerve endings with both vectors. The data suggest that elevation of NT3 levels in the cochlear fluids can disrupt innervation and degrade hearing.

Neurotrophic Factors will most likely not be the answer to restoring neuronal damage to ones hearing. Stem cells differentiated into spiral ganglion neurons on the other hand, could hold the key.

 

[tomytl]

some Genvec news
http://www.genvec.com/media/press-r...reports-second-quarter-2016-financial-results

 

[RB2014]

Neurotrophic Factors will most likely not be the answer to restoring neuronal damage to ones hearing. Stem cells differentiated into spiral ganglion neurons on the other hand, could hold the key.

I am agreed with this and from what I have read it should work for genetic hearing loss and hearing loss associated with trauma or old age. I'm not sure why they are going down the path of testing for chemicals to regrow hair cells when there is a chance that hair cells could grow, but new connections may not be established which basically means either no new hearing or maybe new hearing with no gain in understanding words. I guess that is why they are pursuing all options. I know Neil Segil's lab at USC is working with Stem Cells, but I don't see any updates from the work they are doing.
I'm still excited about the research breakthrough the frequency Therapeutics said they were going to announce, whenever that may be. Right now, though it seems like most of the information, breakthroughs and start-ups are coming from people out of Harvard. I'm not sure why.

"Enrollment is underway in the fourth cohort and we are excited about the product's potential to bring meaningful improvement to patients with severe to profound hearing loss. We believe the trial continues to be on track to be completed in 2017 as previously announced."
Thanks Tomytl. I read that. That is a pretty strong statement. They must know something we don't. Everything we have read and most experts agree that just ATOH1 is not going to cut it.

 

[Reinier]

Stem cells differentiated into spiral ganglion neurons on the other hand, could hold the key.

Yes I think that "coaching" the body to do the repairs is better than targeting one process. It is much more difficult I can imagine, but so much more complete. Instruct stem cells to start regeneration processes.
All lives information is stored in stem cells.
I make it sound so simple.

Another thing I was wondering. Do Stanford, Harvard, etc... share information? Is there competition between universities? Perhaps I have asked this earlier? I can't remember.

 

[Aaron123]

Not specifically research news, but Decibel is growing and moving to a larger space

https://www.bostonglobe.com/busines...ving-fenway/W8H3xpqvLVbQkvRHdxZChN/story.html

http://www.biospace.com/News/year-o...se/428323/company_profile.aspx?CompanyID=1530

Not clear from the two articles how many employees it has/will have. Actually, in a recent article it says "It's still early days for Decibel, but it is aiming to ramp up operations in the next year. At launch, the startup had a staff of 9. Now, at 20 to 25 employees, Holtzman is expecting to grow to 40 to 50 people by the end of this year, and is looking to double that count by the end of 2017." (http://www.fiercebiotech.com/medica...cibel-brings-biogen-vet-steve-holtzman-as-ceo)

 

[fabien]

I've had tinnitus since 2009, I skipped all these years so,

is there a cure soon and can we grow back the cells ? thanks

 

[Reinier]

Good news.
Much needed after a day of horrible hyperacusis (and tinnitus at the moment).
@tomytl already stated that there is much more activity in this field of research (hearing).
I wouldn't know. I "only" have hearing issues for just over a year.
But at Decibel they must have concluded they can grow and Third Rock Ventures was confident enough to invest.

 

[Reinier]

I've had tinnitus since 2009, I skipped all these years so,

What do you mean by "skipped all these years"?
I think I know what you mean, but am not sure.