Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Jim51042]

http://www.cell.com/cell-reports/fulltext/S2211-1247(17)30390-X
This one that you referenced is about hair cells. I never looked at the other one

 

[Jim51042]

"We believe that Dr Rivolta's work is at a more advanced stage than any other research team"

Who would be next "most" advanced in the neuronal stem cell research field?

 

[Samir]

Can you link me to the paper behind the paywall?

I think it was this article in NEJM (New England Journal of Medicine):

http://www.nejm.org/doi/full/10.1056/NEJMcibr1413201

I could probably access it if I really wanted to. I could go to the university library, I'm sure they have a subscription for NEJM. I have access to the library. I am just not motivated enough. I am not a professional researcher. I am just a happy amateur. It's annoying when they put these paywalls up. There are plenty of other articles to read.

 

[jeff W]

Who would be next "most" advanced in the neuronal stem cell research field?

Ha, I couldn't answer that question. But I would take opinions from the Japanese labs and R0bert Jackler's colleagues over at St@nf0rd as a good guide. Although I am sure there are those working on the eye and spinal cord that have a much more comprehensive understanding of neurogenesis and stem cells than what is seen in otology.

 

[jeff W]

I think it was this article in NEJM (New England Journal of Medicine):

http://www.nejm.org/doi/full/10.1056/NEJMcibr1413201

I could probably access it if I really wanted to. I could go to the university library, I'm sure they have a subscription for NEJM. I have access to the library. I am just not motivated enough. I am not a professional researcher. I am just a happy amateur. It's annoying when they put these paywalls up. There are plenty of other articles to read.

Thanks for sharing this, I found it on a google search. I do like to see what others are reading.
goo.gl/4Ab7Pg

 

[Amber]

Robert Jackler and colleagues from Stanford University.

 

[jeff W]

Robert Jackler and colleagues from Stanford University.

Ricci, Jackler, Heller and Grillet.

 

[tomytl]

News from another lab:

https://www.sciencedaily.com/releases/2017/04/170411151001.htm

 

[Samir]

Thanks for sharing this, I found it on a google search.

No, thank you!

Where would we be without Google.

 

[Samir]

Allow me quote some of the key findings from the NEJM article.

"Experiments in mice indicate that even moderate noise exposures can result in permanent loss of synaptic contacts in the inner ear and reduced hearing function.
(...)
A recent study by Wan and colleagues 4 showed that these synaptic connections can be restored with some help from the surrounding glia-like supporting cells.
(...)
The work of Wan and colleagues suggests an approach to repair this damage."

So there we have it! Synaptic connections can be repaired and restored.

Unlike control mice, the mice with Ntf3 overexpression had recovery of both the number and function of their ribbon synapses within 2 weeks. Moreover, when Ntf3 overexpression was not induced until shortly after the noise damage, it was still effective at restoring synaptic connections. These data indicate that noise-induced synaptopathy is reversible, and they raise the possibility that it could be treated even after exposure to damaging noise — an important consideration for the development of clinical therapies.

Impressive! But for how long after exposure?

The synaptic recovery was limited to the regions of the cochlea that respond to high-frequency sounds, and the approach taken in this study probably will not restore hearing function in persons in whom the sensory hair cells have died. Nevertheless, if these damaged synaptic connections can be restored in humans, it could mean improved hearing function for millions of people who struggle with the damaging effects of noise exposure.

Assuming tinnitus is the result of synaptic loss, and knowing that most of us have this high pitch ringing tinnitus, this could mean that this treatment can reduce or even cure tinnitus for most of us.

 

[Samir]

News from another lab:

https://www.sciencedaily.com/releases/2017/04/170411151001.htm

Thanks for sharing!

But it's already been posted. The actual paper can be found in Cell reports.

 

[Cam Cam]

Allow me quote some of the key findings from the NEJM article.


So there we have it! Synaptic connections can be repaired and restored.


Impressive! But for how long after exposure?


Assuming tinnitus is the result of synaptic loss, and knowing that most of us have this high pitch ringing tinnitus, this could mean that this treatment can reduce or even cure tinnitus for most of us.

the last paragraph you respond to about it not working in humans, what is that paper/where did you source it from? cheers!

 

[Samir]

the last paragraph you respond to about it not working in humans, what is that paper/where did you source it from? cheers!

Not working? It says "if these damaged synaptic connections can be restored in humans, it could mean improved hearing function for millions of people". Meaning it has not been tested on humans yet, not that it doesn't work. We will find out if it works once we do the testing. But they are hopeful that it might work just as well as it did in the animal study.

I was quoting the NEJM article. Jeff has posted a link to it. It's that mysterious looking code at the end. It's a short link to the PDF file on his Google Drive account. You can copy and paste the URL into your browser and hit Enter.

If it's easier for you, you can also grab it from this Yimg.com site:
https://xa.yimg.com/kq/groups/59229...tions+in+the+Inner+Ear+after+Noise+Damage.pdf

Yimg is a tracking tool owned by Yahoo. Meaning that link should be safe. My guess is that the article was leaked to Yahoo groups by some individual. It's not the full study, it's just an excerpt from the journal.

 

[Samir]

Who would be next "most" advanced in the neuronal stem cell research field?

I wouldn't know for sure, but here you have 10 possible candidates.

1. Dr Shinya Yamanaka
2. Dr James Thomson
3. Prof. Chris Mason
4. Dr Robert Lanza
5. Dr Douglas Melton
6. Arnold Caplan
7. Alan Trounson
8. Michael West
9. Dr Mahendra Rao
10. Sir John Gurdon

These were considered to be the top 10 stem cell researchers back in 2013. You will find 40 more researchers in the attached document.

I have not studied their work, but the following researchers seem to be involved in neural stem cell research, perhaps more so than others.

• Richard Garr
• Dr Mahendra Rao
• Michael Hunt
• Alan Trounson

 

[Reinier]

Impressive! But for how long after exposure?

Agree.
Also
"The synaptic recovery was limited to the regions of the cochlea that respond to high-frequency sounds,"
We don't know if that is because the NTF-3 did not reach further in the cochlea.

"and the approach taken in this study probably will not restore hearing function in persons in whom the sensory hair cells have died."
That to me is so obvious. How can you restore synapses on non existing hair cells?
This research is already more than 2 years old.

 

[jeff W]

I wouldn't know for sure, but here you have 10 possible candidates.

1. Dr Shinya Yamanaka
2. Dr James Thomson
3. Prof. Chris Mason
4. Dr Robert Lanza
5. Dr Douglas Melton
6. Arnold Caplan
7. Alan Trounson
8. Michael West
9. Dr Mahendra Rao
10. Sir John Gurdon

These were considered to be the top 10 stem cell researchers back in 2013. You will find 40 more researchers in the attached document.

I have not studied their work, but the following researchers seem to be involved in neural stem cell research, perhaps more so than others.

• Richard Garr
• Dr Mahendra Rao
• Michael Hunt
• Alan Trounson

Yamanaka, imagine we had him in otology.

 

[Samir]

We don't know if that is because the NTF-3 did not reach further in the cochlea.

We would know if we had access to the whole paper. That was just an excerpt. But I would assume that this is because they could not deliver the NT-3 effectively to the apical part of the cochlea. So they may need to improve the delivery method.

This research is already more than 2 years old

True! Let's hope they have made progress since then, perhaps they have an improved delivery method now? I certainly hope so.

Yamanaka, imagine we had him in otology.

Imagine if Frequency or Decibel hired him!

 

[Samir]

@Jim51042

Here are some more noteworthy names:

• Sally Temple
• Brent A. Reynolds
• Samuel Weiss
• Constance Cepko
• Evan Y. Snyder

Here is a short description of their importance:

In 1989, Sally Temple described multipotent, self-renewing progenitor and stem cells in the subventricular zone (SVZ) of the mouse brain. In 1992, Brent A. Reynolds and Samuel Weiss were the first to isolate neural progenitor and stem cells from the adult striatal tissue, including the SVZ — one of the neurogenic areas — of adult mice brain tissue. In the same year the team of Constance Cepko and Evan Y. Snyder were the first to isolate multipotent cells from the mouse cerebellum and stably transfected them with the oncogene v-myc. Interestingly, this molecule is one of the genes widely used now to reprogram adult non-stem cells into pluripotent stem cells. Since then, neural progenitor and stem cells have been isolated from various areas of the adult brain, including non-neurogenic areas, such as the spinal cord, and from various species including humans.

Source: https://en.wikipedia.org/wiki/Neural_stem_cell

 

[Jim51042]

@Samir This is great news. Are these supporting cells listed this NEJM article the same ones that Frequency induces? Does Frequency's newly created hair cell also have supporting cells they are contain within? How many synaptic connections would a newly create Frequency hair cell make?

Does the supporting cells with this growth factor create synaptic connections to dead hair cells or does the body know when a hair cells is dead and not use up synaptic connections to it. I hope the latter but has this been proven? Would tinnitus exist if synapses were connected but connected up to non-function or semi functional hair cells? Do dead hair cells remain and if they get absorbed how long after death does this process take? Can semi-functional hair cells exist or is completely effective or dead the only options for hair cells? Can we get a non-invasive uOCT probe today so researcher, this forum, and I are inferring the based on cloudy data?

"The authors generated conditional mouse models in which Ntf3 expression was increased specifically in cochlear supporting cells."
How was Wan able to do this? If viral vector then can some lab test out on a primate NT-3 induction of the supporting cells via one of these viral vectors (ANC80 whatever etc). Please!!! If a test showed synaptic connections in primates would be game over for tinnitus/hearing loss via noise damage.

I still think the combination of gene therapy inducing production of NT-3 and BNDF in the supporting cells weeks before and shortly after a Frequency dosage is the clear best answer to hearing restoration with the current technology. I been thing over the past weeks that cooperation and coordination between Decibel and Frequency would enhance both of their treatments. Do companies like these coordinates without a merger? Maybe one can buy out the other or vice versa. Regardless with the big if that both companies have viable treatments in 1.5 years I would recommend people with noise induced hearing loss start a Decibel treatment before a Frequency treatment.

 

[Samir]

These are the references used in the NEJM article above:

• Hickox AE, Liberman MC. Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus? J Neuro-physiol 2014;111:552-64.

• Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss. J Neurosci 2009;29:14077-85.

• Wan G, Gomez-Casati ME, Gigliello AR, Liberman C, Corfas G. Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma. Elife 2014 October 20 (Epub ahead of print).

• Moser T, Predoehl F, Starr A. Review of hair cell synapse defects in sensorineural hearing impairment. Otol Neurotol 2013;34:995-1004.

Look familiar? I tell you what! We will owe it to this man one day! In fact, we owe him already.

 

[Aaron123]

Allow me quote some of the key findings from the NEJM article.

This research is already more than 2 years old.

We would know if we had access to the whole paper. That was just an excerpt.

Does anybody here actually read papers? The NEJM paper is just a commentary/explanation of a paper published in 2014. There is NO research in the NEJM paper. I have no idea why people are focused on a discussion of a 3 year old paper.

 

[Samir]

Does anybody here actually read papers? The NEJM paper is just a commentary/explanation of a paper published in 2014. There is NO research in the NEJM paper. I have no idea why people are focused on a discussion of a 3 year old paper.

You mean the ones I posted above?

I thought it was an original study that I just happened to not have access to. Thanks for clarifying! I sort of figured that out, but a bit too late.

So it was only a commentary? Is that a real thing in academia? They post commentaries like these in journals? Sorry for all these questions, I am not too familiar with how academic publishing works.

So they want 20 USD for commentary. I thought that was too cheap to be good! They could have posted that elsewhere on the web and it would have been free for everyone to read.

 

[Jim51042]

Look familiar? I tell you what! We will owe it to this man one day! In fact, we owe him already.

If a treatment to cochlear neuropathy develops and Frequency is successful I would expect a noble for Liberman, Karp, Langer, and maybe others will receive a noble along with a lot more research money. So not just from TT but they will get worldwide accolades.

 

[Samir]

If a treatment to cochlear neuropathy develops and Frequency is successful I would expect a noble for Liberman, Karp, Langer, and maybe others will receive a noble along with a lot more research money.

I don't think there can be more than three who share the same prize.

That's Nobel by the way, with capital N.

 

[jeff W]

I don't think there can be more than three who share the same prize.

That's Nobel by the way, with capital N.

They give out prizes to at the B@rany and the Pr0sper Meniere's society, a prize for this and a prize for that. So while they are busy feeding their narcissism with shiny medals patients are out there suffering, some committing suicide. Forget the prizes, how about we shut the funding off for the labs that don't produce. The current holder of the prosper meniere's s0ciety gold medal is in love with his own work so much, that he plasters his own references across all his publications, lots of papers, lots of ear theory and not one single treatment for anything, yet he gets funding for publishing frequently while younger more ambitious scientists get nothing. I still believe the patient body needs to make its presence felt in a powerful manner to deal with those who seem to be lost at sea. The funding is the weak spot of the research arm that can be exploited to control its direction.

 

[Amber]

Wtf is wrong with this jeff w dude?? Why does he mask the names????

Barany and the Prosper Meniere's Society Gold Medal

 

[Samir]

I was not aware of the Prosper Ménière Society or that they have a Gold Medal Award.

For the curious minds out there, check this site:
http://prospermeniere.com/awards/

Just for the record, "B@rany" most likely refers to Róbert Bárány, an otologist from Austria-Hungary who received a Nobel prize in 1914.

For the curious minds, check here:
https://en.wikipedia.org/wiki/Róbert_Bárány

Wtf is wrong with this jeff w dude?? Why does he mask the names????

Don't you think that's inappropriate? If you really want to know, you can ask him directly. Why are you using so many question marks? You can use the button in the upper left corner of the toolbar to make text appear bold, for emphasis.

Jeff can correct me if I'm wrong. But I think the @-sign (at sign) in "B@rany" indicates "crazy" and "Pr0sper" indicates "looser". I can see why he would send a message like this.

So while they are busy feeding their narcissism with shiny medals patients are out there suffering, some committing suicide.

When I first started having tinnitus I could not believe some of the horror stories I found on the web. I feared that I would take the same path. I knew only vaguely what tinnitus was, but I never thought that it could drive people to madness like that.

Forget the prizes, how about we shut the funding off for the labs that don't produce. The current holder of the prosper meniere's s0ciety gold medal is in love with his own work so much, that he plasters his own references across all his publications, lots of papers, lots of ear theory and not one single treatment for anything, yet he gets funding for publishing frequently while younger more ambitious scientists get nothing.

This current holder you refer to, that would be Joel A Goebel? I have never read anything about him. I will have to check your claims. But it's never a good sign "plastering" your own references on your own research paper.

I concur that some of these researchers only seem to be interested in perpetually fueling their own curiosity. That's how I would put it. With little to no interest in translating the findings into treatments. I agree that this is not fair on the young, aspiring researchers.

Personally, if I was a researcher I would be more interested in perusing research with the goal of finding some kind of cure for a certain disease, or something that makes the disease more manageable. I would like that more than a medal. It's nice to be appreciated and recognized, but what better recognition is there than being the one who cured a certain disease for example. That doesn't have to mean that I lose my job. There is always more to be done to improve treatments, or switch to a different research area.

I still believe the patient body needs to make its presence felt in a powerful manner to deal with those who seem to be lost at sea. The funding is the weak spot of the research arm that can be exploited to control its direction.

I saw the link you posted earlier. This is very interesting and inspiring.

 

[jeff W]

I don't know what is and what is not indexed on google searches so I just don't want to attract unwanted attention to this site, that's all.

I have no problem with G0ebel. It is the older members that are hanging around well past their usefulness. We must have a constant stream of youth arriving at these labs. I will soon be posting a speech from a patient who has tried to outline the sort of problems I refer, his story is remarkable.

 

[jeff W]

Regards

The great and masterful

Jeff W
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[Jim51042]

I missed this from the New Yorker Article. It seem Liberman is very optimistic and confident about future neuronal re-connections. When he is talking about local delivery does that mean growth factors or some other substance that hasn't been disclosed(maybe by Decibel )?

http://www.newyorker.com/magazine/2017/04/03/high-tech-hope-for-the-hard-of-hearing

"Nonetheless, among researchers, the discovery has been a cause for optimism, because reconnecting nerve synapses is almost certain to be easier than regenerating functioning hair cells inside human ears. "This is the simplest sensory circuit that you could possibly have," Liberman said. "It's one sensory cell type and one neuronal cell type, and it's possible to do local delivery through the eardrum." He and others have successfully restored some damaged connections in lab animals, and he believes that far greater advances are to come. "In the past five years, there's been an explosion of biotech companies getting serious about the inner ear for the first time," he continued. "I think most people in the field would say it's no longer a question of if we will be able to unlock enough of the secrets but merely a question of when.""