Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Paywalled. Any chance you can copy and paste the "news"

 

sorry guys, now there is indeed a paywall, it wasn't before...

 

“Tiny particles that deliver drugs to the hard-to-reach inner ear have been developed by Melbourne researchers in an ambitious project to develop the first preventive treatment for the most ...“
- and that’s all I could see via google search results. Is it that article?

 

Inner Ear Hair Cell Damage — Maybe We Can Know More

I would be glad to know, whether my tinnitus is due to inner ear cell damage, - or not.
If not, I don't need any hair cell regeneration....

 

Nanoparticle research offers glimmer of hope for deafness sufferers

TINY particles that deliver drugs to the hard-to-reach inner ear have been developed by Melbourne researchers in an ambitious project to develop the first preventive treatment for the most common type of deafness.

A team from the Bionics Institute and University of Melbourne has developed porous particles — about the size of Hundreds & Thousands — that are loaded with medication and delivered through the ear drum and into the cochlear, to protect the easily damaged sensory hair cells that convert sound into nerve impulses.

Preclinical studies have shown that delivering these growth factors into the inner ear can restore the loss of connections between neurons and sensory cells — just like reconnecting the lead cable to a microphone.

Now, a $680,000 National Health and Medical Research Council grant will fund the crucial final preclinical studies aiming to test whether the treatment delivers functional benefit, in order for a first trial in humans.

Senior research fellow Dr Andrew Wise said hearing aides and cochlear implants were the only treatments for sensorineural hearing loss, which affects the volume and clarity of sound, and makes discriminating words from background noise hard.

But given hearing aides only amplify sound and don’t made words clearer, and that a third of cochlear patients inexplicably lose their remaining natural hearing, better treatments were needed.

“It’s known as ‘hidden hearing loss’, because it’s not reliably detectable,” Dr Wise said.

“And yet, it’s severe hearing loss that’s an important factor in the progression of neurological diseases like dementia.”


Senior research fellow Dr Andrew Wise is one of the scientists behind the nanoparticle research.

Dr Wise said their drug delivery technique helped overcome two major challenges of delivering medication to the inner ear: firstly, protecting the medication so it could diffuse over weeks or months; and secondly, by allowing the drug to stay close to sensory cells rather than being drained through the tubes connected to the throat.

“It’s about finding that early therapy so you can go in, repair and regenerate those connections, when it hasn’t progressed to such a degenerative state,” Dr Wise said.

“Once you lose those hair cells at the moment there is no way to replace them. But if we can repair some links, you can perhaps slow progression and improve hearing.”

ENT surgeon Sheryl Wagstaff, a co-investigator on the project, said she had seen how hearing loss quickly lead to social isolation, which increased the risk of dementia.

“I used to say to patients; there’s not going to be anything I can do for you in my lifetime. Just recently I’ve been saying; there might be something on the horizon,” she said.


Dr Andrew Wise has a close look at some of the nanoparticles.

 

So the drug's aiming to fix the synaptic connections, isn't it? Cool, then, we got a new player on the board (the fourth? fifth?), although it's a shame they didn't say anything about human clinical trials.

 

I imagine if a real cure for hearing loss would happen, it would have to first repair the nerve synapse connection then regrow the hair cells for the most optimal results

Perhaps Frequency-tx will work with these guys in the future to tackle both issues relating to hearing loss.
What I fret is that Frequency-tx might fail clinical trials because without repairing the connections first it might not make much of a difference. I don't know anything tbh, I'm just speculating here.

 

Agreed, but new hair cells are expected to create new synaptic connections, too. I guess we'll have to wait...

 

I'm really happy and hopeful for those people suffering from noise induced tinnitus. Stay strong until the cure comes out.

 

It's exciting to read all the news and see that already a hand full of candidates are in the clinic. The main difference compared to 10 years ago is the fact, that most therapies are trials of a new class of therapy, not something you swallow and maybe reach the inner ear probabl do something. It's precise delivery with unbelievable complex compounds.
It still will take it's time and still has to proof as therapeutical relevant...ut exciting times....

 

From what I heard from people on the forum 10 years ago there was very little research and no mention of trials at all.
Now it seems more promising then ever for hearing loss/tinnitus research.

I am excited!

 

“It’s about finding that early therapy so you can go in, repair and regenerate those connections, when it hasn’t progressed to such a degenerative state,” Dr Wise said.

Lets imagine this works, 8-10 years from now when the trials are finished and it's on market.
Everyone who has hearing loss now and wants nerve repair will be considered in a "degenerative state"

 

That's indeed frustrating. But if it works, the delivery could probably be used for other therapies with different compounds too....and for people in the acute state would it be perfect

 

What a coincidence that FT are doing the first clinical trials in Australia. Also using the round window to get growth factors in the inner ear.

 

I guess, most important, that at least one compound can cure a little in the ears with a clinical relevance.
This would be a first important step and also gaining much much more funding/developing/innovation
We can't expect the 100% cure for the beginning. I guess it comes in several steps.
Maybe I would be happy if I could take a pill to keep my hearing threshold stable, and in 15 years some regeneration or lowering tinnitus... we just need a company with the first causal treatment for inner ear diseases.

And many are on the start:
-Auris Medical
-Otonomy
-Sensorion
-AudioCure
-Audion-tx
-Decibel-tx
-Frequency-tx
-Novartis (cgf-166)
-Roche (Inception3)
-Sound Pharmaceuticals
-Quark Pharmaceuticals
-Affichem
-Otologic Pharmaceuticals
-Acousia
-O-Ray Pharma
-Oricula-tx

and probably some more I don't know or forgot....

 

Damn, that's a lot more companies than I thought.

 

The degenerative state could imply when the synapses/nerves are dead and not damaged.

According to recent comments, this could take decades before they officially "die". So don't lose too much hope.

 

I need facts, not wishful thinking in the comments section. So are any of the "recent comments" backed up with anything credible.

I did a Google search on Dr. Wise and found out he is a Senior Researcher at "Bionics Institute" in Australia. The organization is mostly focused on bettering the technology of Cochlear implants. It also seems his drug is more designed to go hand and hand with a Cochlear implants then be used on its own. There is no mention of hair cell regeneration projects from Bionics Institute or teaming up with a bio-tech company like Frequency Therapeutics to tackle all issues of hearing loss.

 

Watch or read up on Liberman's research, that way you can hear it "from the horse's mouth".

 

View attachment 14295
Source: Saager & others (2017) referencing a 2002 paper by Felix, H., Pollak, A., Gleeson, M. & Johnsson

 

http://www.aro.org/page/KujawaLiberman

“... the cell bodies and central axons of cochlear neurons, survive for years to decades despite their loss of functional connection to the hair cells.”

I believe the “degenerative state” occurs when the cell bodies die; at that point, the synapses have nothing to connect to.

I also liked the very last line:

“Of all the regenerative strategies for hearing impairment envisioned in our field today, we believe that treatments for cochlear synaptopathy will be the easiest to achieve.”

 

some news from H.Löwenheim, one of the pioneers in hair cell regeneration.
It's in german language
http://news.doccheck.com/de/199497/nachgeforscht-wenn-gehoerlose-wieder-hoeren/

 

Can anyone translate it?

 

Fibroblasts, reprogramming, pluripotent stem cells and suddenly hear again? What sounds like disconnected words might soon become reality. Professor Löwenheim from the University Hospital Tübingen reports on current research.


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Investigated: When deaf hear again?
on DocCheck TV


The video content in transcribed form:

Prof. Dr. Hubert Löwenheim: "About 15 years ago it was discovered that stem cells can be isolated from the inner ear. After isolation of these stem cells, these stem cells grow into mature hair cells, at least in vitro, and can also be transplanted into an intact ear. In addition, as a result of these research results it was also shown that the hair cells are also formed from so-called pluripotent stem cells.

Here we distinguish two classes: once embryonic stem cells, but also the so-called induced pluripotent stem cells , which can be obtained by so-called reprogramming from skin cells or from fibroblasts. And hair cells derived from pluripotent stem cells also show similar properties to normal hair cells. This led to the idea of transplanting these stem cells into the diseased inner ear.

The problem with this research approach, which seems very attractive at first, is that the stem cells to be transplanted naturally have to find the place in the inner ear where they should fulfill their function. If that succeeds, they would have to be differentiated into hair cells when they arrive at the place.

These two problems have not yet been solved, so the idea of using stem cells directly as a therapeutic is still a vision of the future. The second benefit that comes from this stem cell technology, however, is that we now have hair cells available in vitro, and in large numbers. It is true that the inner ear, for example of the human, contains only 15,000 such sensory cells and of course I can not win them for experimental purposes. That would only be possible post-mortem, after dying. Therefore, such cells are not available for research.

Thanks to stem cell technology, however, these cells have been made available for research purposes in vitro and pharmacological drug discovery has begun at these cells. This kind of research is already under way and is the first to allow screening of inner ear cells for pharmacological agents.

Question: Which functions can be restored?

In direct transplantation, of course, that would be the replacement of lost neurons or hair cells. These sensitive cells can be lost through the aging process, toxic drugs or other environmental factors such as noise trauma. That would be, if that would work, a field of application.

The second technology that I have addressed, namely pharmacological drug discovery, is essentially the study of the toxic effects of certain drugs that can be investigated here. If these toxic effects are known, protective drugs could also be found. For example, in the treatment of malignant tumors we use an ototoxic drug with the active ingredient cisplatin - for example, we could find substances that counteract the ototoxic effects of cisplatin with these stem cell technologies.

Third, we can also find regenerative substances in these drug trials. Also in the field of regenerative medicine of deafness there are currently two clinical studies: First, a gene therapy approach is used here, with the help in the inner ear remaining support cells converted into hair cells, that is to be converted, which should then resume their function , Second, a pharmacological approach is used to convert or convert the same support cells into hair cells as well. These are the first interesting therapeutic approaches that are already being tested in clinical trials, but it will be several years before results are available.

For which patients does this new approach come into question?

Basically for the large group of patients with sensorineural deafness or sensorineural deafness, that is, patients suffering from loss of their sensory cells or other structures in the inner ear.

The largest group of these patients are patients with senile hearing loss , called presbycusis . Presbyakusis, in turn, may be responsible for the loss of sensory cells, the loss of nerve cells, or the loss of so-called supportive cells that may be required to sustain the battery in the inner ear. The treatment of these cell losses could take place on the one hand protective, that is, one prevents the loss of these sensory cells, or by regenerative means, that is, these sensory cells are re-formed after loss and resume their function. That would be a so-called regenerative therapy approach.

It can be stated that the currently available technologies of mechanical supply and electrical supply produce very good results and that the future expected biological regenerative therapies are certainly interesting for the patients. But that should not stop us from actually using the technologies now available on the patient.

 

Anyone seen an update with the REGAIN eu project ? Last I’ve seen was that they were recruiting

 

See the other threat:

https://www.tinnitustalk.com/threads/audion-therapeutics-trial.21830/page-5

It looks like they completed phase-1. Maybe they already know more about effectiveness as 24 patients participated in phase-1.

 

Otologic Pharmaceuticals updated their pipeline on it's site with some info of their regenerative program for acute and chronic hearing loss. They also mentioned, that they are testing their approaches for tinnitus too.

http://otologicpharmaceutics.com/pipeline/

 

https://www.sciencedaily.com/releases/2018/02/180208104227.htm

New article.

iPS cell-derived inner ear cells may improve congenital hearing loss

 

Interesting Event coming in March
https://www.actiononhearingloss.org...earing/translational-hearing-research-summit/

 

exactly. very frustrating. I suppose they could get an image of the damage in my inner ear after autopsy (but they wouldn't bother would they?)

The science for this kind of imaging (through the living cochlea) can't be that far off is it?