Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Do you have details about the "short window" to restore the connection between hair cells and nerve terminal ? I want to believe this window is not so short... What's the point of hair cells regeneration otherwise ?

If we create new haircells, we have to connect them to something...

 

Good question, I was about to ask the same. Technically, if we can connect a cochlear implant directly to the nerve terminals, that would implicate we can also connect new hair cells directly to these nerve terminals. If I understand correctly, @HomeoHebbian mentions the CI directly stimulates the nerve terminals and there is a much longer window of opportunity for that. Why wouldn't that same window of opportunity exist for re-connecting hair cells (unless these die off after being disconnected for a while) with NT-3 or connecting newly-grown hair cells?

Unless the nerve terminal itself is damaged, but that could mean the stimulation with a CI wouldn't be beneficial as well, right?

 

Don't you think that in general, the synapses are not well explained ? We always hear about hair cells and cochlea nerve, but not much else. The cochlea is a lot more complex than that and I must say I'm a little confused. Is there a website where everything is clear and complete ?

I'd like to contribute more to this thread but I have to learn the basics.

 

The information I got when I first had an appointment with the hospital here that specializes in Cochlear Implants was quite different from my second visit to meet the surgeon who will eventually be surgically implanting me with one of these bad boys.

What I was told in the beginning is, if you have no tinnitus or have it very mild, the implant has been known to increase tinnitus in many patience. Upon my second visit to meet the surgeon, he informed me that since my tinnitus is severe and always there 24/7, the implant will most likely reduce the amount of tinnitus in that side (ear). It seems there is always some tinnitus with an implant and if yours is really bad, it should bring it down to the NORMAL implant level. If you have none and are getting one simply because you are deaf, it will give you tinnitus at a NORMAL level. I forget how many out of 100 he said it was, but I remember it was a fair number of patience who experienced it.

Now lets chat a bit about other risks with the implant. 4 out of 10 patience who have the implant experience a change in taste along the side of the tongue. Apparently anything you eat, or drink that touches the side of the tongue including water, will taste like metal if your one of the lucky 4 out of 10. Worst case scenario you actually could lose all taste in your tongue however the numbers are very low. When they install the electrode into the Cholera, they mus cut into an area that has 4 main nerves. Two are for the tongue, one is for the feeling in that side of your face, and the other controls eyelid function. They MUST cut one of these nerves! So almost everyone experiences a temporary taste change in the beginning but somehow in 6 out of 10, the other tongue nerve somehow adapts and takes over from the damaged tongue nerve.
Now lets say the surgeon happens to nick the facial nerve or eye lid nerve, you could lose all feeling along one side of your face or have a hard time with the eyelid. No matter what, they HAVE to cut one of these nerves to get into the Cholera.

In my case, the rewards far outweigh the risks. I am now completely deaf in both ears other than "residual" hearing in my right ear, and have the worse tinnitus in both ears imaginable. I am not getting this implant to rid or reduce my tinnitus, but to be able to hear somewhat again. The hearing is not normal like is stated in a post above, but you get used to the new kind of hearing over time. Music wont sound the same, voices will be different, etc, but at least I will understand people, be able to make a phone call again, go to the movies again, watch television without close captioning again, hear the engine in my car again.................... you name it!

Average price for the implant, surgery and 1st year of follow up tuning and therapy is about $60,000 Canadian. Luckily this is covered in my province. However every 4 or 5 years they come out with a new and sometimes improved receiver for the implant and if I wished to upgrade, that comes from my pocket, anywhere from 10-15 grand. You also need to keep the batteries charged or replaced, like a hearing aid, and God forbid you lose the receiver or damage it in water etc. Now if you need one in each ear just to reduce tinnitus, that's $120,000.

Because of our health care system, only one implant is covered. I sure would love to have both ears done but that means much out of pocket expense for the second one. No upgrades are covered so I pay to upgrade the receiver over time.

Not sure I would even consider this just for tinnitus. To many risks and if you can hear normally somewhat, that hearing will change!!

 

Lets not forget, when they install the receiver and electrode, the receiver is placed under your scalp. They make a large incision behind the ear from top to bottom and then again towards the back of the head. They fold back the flaps of skin and DRILL an indent into your skull where they fit the receiver. It's a fairly large area of skull they must grind down. Once they fit the receiver in the indent, they feed the wire and electrode into the Cholera. After that is done they stitch yea up, wrap your head like a mummy and send yea home. After a few weeks of healing you go back and have the stitches removed and get the external sound processor. Thats when they first TURN YOU ON! Then you have to go back often to have the software tweaked many times.

 

In my first response above I said receiver in many places. What I meant was "sound processor". The receiver never gets changed or upgraded unless somehow it fails as it is inside your scalp!

 

If there isn't a thread dedicated to CIs, it might be useful to start one so that this detail doesn't get lost in this thread and that this thread doesn't get sidetracked by all of the detail on CIs.

 

This is what I recieved from Maison regarding detection of hidden hearing loss:
'We're currently in the process of getting fund to start an important study that would ultimately (if successful) give us good tool to detect hidden hearing loss in human patients. I don't expect to being recruiting participants until Summer/Fall 2017'
It means at least a year before a reliable detection tool is available to be tested on humans. We need to be patient.

 

Inner hair cells convert mechanical vibrations into a chemical 'message'. That message is transmitted through a tiny synaptic cleft (~0.001 millimeters) and picked up by the auditory nerve terminal. The auditory nerve transmits this signal to the brain...and well, the rest should be left for another post. You can't restore the communication between an inner hair cell and a nerve terminal (and hence to the rest of the brain) unless they are in very close proximity (0.001 mm). When hair cells die the nerve terminals retract. So, yes, this is just one of several major roadblocks for hair cell regeneration therapies. Cochlear implants work differently. The electrode is threaded into a different compartment of the cochlea and the electric current stimulates a more "proximal' part of the nerve trunk. In other words, even if the nerve has retraced too far from the inner hair cell to support synaptic transmission, it is still possible to bypass the hair cell and activate the nerve directly. ...hope that helps.

 

Thank you, this indeed clears up some confusion but also raises some new questions unfortunately.

I would greatly value your input on the following questions. The questions kind of depend on each other. I have been thinking and wondering, but may of course be headed in a completely wrong direction here.

• Do you think there is any relation between the damaged nerve terminals and the perception of Tinnitus?
• If so, could Tinnitus perception be caused by malformed interaction between damaged nerve terminals and loosely connected/disconnected hair cells as one of it's many etiologies?
• If so, could the retraction of the damaged or disconnected nerve terminals ultimately alleviate Tinnitus? This retraction appears to be a very slow process and some people have reported Tinnitus remission after longer periods of time (years/decades).
• And if so, could temporary Tinnitus (as experienced with a temporary treshold shift (TTS)) be caused by loosely connected nerve terminals that manage to reconnect to their hair cell after a short while?

Excuse me for the many questions I have regarding this matter. I'm sure a lot is not clear yet, even to researchers in the field, but maybe you can give your view on this. I would like to thank you for your time so far.

 

@HomeoHebbian, @Vinnitus: Those are great points and questions. So hearing restoration will undoubtedly be a two step process of rebuilding the hair cells and getting the appropriate nerves to reconnect to those cells?

 

https://www.actiononhearingloss.org...zareitn2otvppqlhhtgcsre5mnt5hqj6nj0ftbyjloiiy


https://www.actiononhearingloss.org...zaREitN2OTVPpQLHhtGCSre5mNT5Hqj6NJ0ftbYjloiIy

Found some new articles that I don't think have been posted tonight.

 

I agree. I would really like to know which of the two spiral ganglion neurons perform what and where they connect to back in the brain.

I've posted this website on TT an appropriate amount of times. It talks a good bit about the mechanisms involved in our hearing and also about hyperacusis: http://hyperacusisfocus.org/innerear/

 

I think this is worth mentioning: http://hearinghealthfoundation.org/blog?blogid=251
Another tiny step closer to regeneration.

 

@Reinier

Looks promising for future hair cell regrowth. Sunnybrook Health Sciences is one of the leading research teams and works closely together with the University of Toronto. Sunnybrook is where I will be having my Cochlear Implant done and I feel very fortunate to live quite close to Toronto and am able to have my surgery and Implant done here. This team is amazing and full of dedication and knowledge. They are one of the top 3 in the world today in hearing related treatments. What I was told when I met the surgeon is, they have a 100% batting average to restore at least some hearing in the deaf with a Cochlear Implant. Not many other hospitals around the world who performs this surgery has such a high rate of success.

So any news and research that comes from Sunnybrook should be taken seriously. These guys and girls know their stuff and know it well. Fingers crossed they find a way to get those supporting cells to multiply and begin to grow new hair cells!! Good article and glad you posted it!! Cheers

 

@Nick Pyzik : fantastic website, thank you.

And yes, good one @Reinier . Let's multiply the supporting cells and get some new hair cells, WITHOUT loosing the supporting cells, which is the main flaw in the Genvec / Novartis trial if I got it right.

If you loose your supporting cells, you have no chance to get a better treatment one day.

 

If I lose my supporting cells but I recover my hearing and drop the tinnitus, then what possible better treatment would I want in the future. I'm golden.

Like they say "a bird in the hand is worth two in the bush" - ou en Français: "un tiens vaut mieux que deux tu l'auras". Severe ear problems in life are rare. Two ear problems in life are rare squared. Sure, I'll die with no supporting cells left, but why should I care? Won't be needing them in the afterlife.

I'll take a working cure now even if it means I couldn't take another cure later, should I get another ear disease.

Statistically speaking, you're better off getting cured now and enjoy as much as possible from your life now.

That's my take on it.

 

Of course, but the Genvec/Novartis trial is far from being able to restore a great amount of hearing.

 

In that case I don't consider it a cure (yet)...
It's possible the initial data isn't great, but gives pathways to optimizations. If small improvements are possible, there's a chance bigger improvements can be achieved.

 

Yes that's what I meant. We are not far away from new clinical trials, but this experimental phase will last a bit. I'd like to take part in a regeneration trial soon (like Audion's), but there are so many risks that they'll certainly choose people who are almost deaf only.

I also wonder what a cochlea would look like without supporting cells. Maybe they are needed even if they are not "active" cells.

 

Well, it depends on what you call a "severe ear problem", of course. For me, chronic tinnitus can be classified as a severe ear problem (or a brain problem originating in the ear), and you will be amazed how easy it is to acquire that one in our noisy society.

Unless you plan on getting the treatment and locking yourself up from the outside world, of course...

If it happens once, it can happen again. What can go wrong, will go wrong (Murphy's law).

So I kind of disagree with the rarity of that and hence; we should strive for treatments that leave our future options open.

But, at the other hand...

I am not sure if losing your supporting cells will be such a big deal further down the line. If stem cell treatments become a thing for inner-ear treatments, new supporting cells could perhaps be made.

 

100% is impressive.
Good to know that researchers with an excellent track record who are dedicated, are searching for hair cell regeneration mechanisms.

 

I understand that you don't want to loose to many support cells. Actually there would not be a cochlea without support cells. Not only mechanical support, but also needed to keep hair cells alive.

Let us hope we underestimate the researchers at GenVec. They would have known from the start that support cells are needed and perhaps were able to address this. I personally rate the knowledge of these researchers high and would almost place them on a pedestal. Almost
The researchers that come up with a robust hair cell regeneration "cocktail" I will place on a pedestal.

 

Just did a test in the last few days using the stored Diazepam tablets I have saved up over the past couple of years. The only medication I allow my GP to prescribe is diazepam 5mg. He prescribes 30 tablets per month to be taken once daily. However I hate being on any benzo's and have only taken 1 or 2 per week on my bad anxiety days. So here is what I tried and do NOT recommend this to anyone else who suffers severe tinnitus like myself. Like I said before, I am completely deaf at the moment in both ears and have a nasty loud high pitch screech in each ear.

3 days ago I decided to try to take 2-5mg tablets twice a day. Needless to say I feel like a bit of a zombie and somewhat numb. The first day I noticed zero decrease in my T. The second day of taking a total of 20mg over the course of the day, I found my tinnitus lower and not so high pitched. The third day (yesterday) I took the final 20mg of Diazepam. When I woke up today quite groggy, my tinnitus was much lower. Low enough to the point it was no longer driving me insane.

Here lies the catch. These benzo's are highly addictive. Also over time if you take higher doses they have been known to work the opposite, maybe not on tinnitus, but on anger. What is meant to relax you can actually make you more angry and irritable. So if your T is really bad and you have some left over diazepam, you may get a day or two of relief but do it much longer and you get other nasty effects.

Today I stopped any benzo and will use just melatonin supplement 3mg, in the evening to help me get to sleep easier. This was simply a test on myself and no way in heck would I continue to use diazepam in such a high dose. Same them for the worst days only and store the rest for the future when my GP may decide to stop prescribing them.

Don't ask me why I had a decrease. Maybe because I was less stressed? Maybe because I got more sleep? Who knows. Just wanted to share this with my friends in the community here.

 

I know about Murphy's law, but it's not rooted in any statistical reality. It's a "law" that is being brought up to foster preparedness. For sure, if it happens once it can happen again, but again, statistically speaking, it probably won't, because it's rare.

We as people are really bad at assessing risk.

With billions of people on earth, it's pretty obvious that some folks will have the "one in a billion problem": I'm not claiming it won't happen somewhere on earth, but the odds of happening to you are infinitesimal, just like winning the lotto mega-jackpot.

So again, if you're foregoing a current cure because it could ruin your chances of curing you a second time, should you get that same rare condition, you're making an emotional choice, not a rational one.

 

Nobody argued we shouldn't strive for treatments that leave our future options open.

 

You might get more interest if you posted this in a benzo thread in the support area. This doesn't seem to have anything to do with research on the inner ear.

 

Gene Editing:
http://www.genengnews.com/gen-articles/gene-editing-gives-gene-therapy-a-rewrite/5830/

 

That's it. I will never consider myself cured, even if my hearing loss, T and H all disappear. I'll keep in mind that my ears are fragile and that the whole thing can start again very easily. But it would be a delight to know how precious my new ears are.

 

New ears. I like the sound of that. Pun intended.