Inner Ear Hair Cell Regeneration — Maybe We Can Know More

[Samir]

That was what I was referring to (-;
http://www.the-scientist.com/?articles.view/articleNo/43804/title/Inner-Ear-Cartography/
When I read the following in this article: "Within the mammalian cochlea, apical cells retain regenerative capacity for a few weeks after birth, but basal cells do not."
This was in 2015. By now researchers should have the information what the difference is between these cells?
Most inner ear hearing loss is in this area.
What makes it such a challenge?

Yes, the "Inner Ear Cartography" by Heller et. al. has been published in 2015. I think that was a major breakthrough. Simply put, many of the general types of cells such as outer hair cells display genetic differences along the sensory epithelium.

One of the findings in that same study was that "apical cells retain regenerative capacity for a few weeks after birth, but basal cells do not". Apical cells are closer to the apex of the cochlea and correspond to low frequencies. Basal cells are closer to the base or the entrance to the cochlea and correspond to high frequencies. So what's the difference? Why do for example outer hair cells at the apex display regenerative properties, while the outer hair cells at the base do not? Also, what causes the basal cells to loose their regenerative properties?

Most of the hearing loss happens at the high frequencies. This is thought to be because of their close proximity to the sound source. But the genetic properties might also play an important role in the death or survival of high frequency cells. This brings on the question of whether or not genetic predisposition makes some people more tolerable to high frequency hearing loss?

These are all great questions! But I can't answer them yet. We know a lot more about these cells. But we still don't have a full picture. Helge Rask Andersen worked on mapping the nerve cells in the cochlea, and he also discovered that there are genetic and functional differences between them, depending on what frequency they signal to the brain. So they are not just a bunch of nerve cells here and there. Each one is unique and has an important role to play.

These are important realizations! Even if we don't fully understand it just yet. To quote Socrates, "True knowledge exists in knowing that you know nothing."

We need to dive deeper and learn more. Decibel Tx seems to be expanding on this previous work.

On the Otostem project website, they state:

The lack of human otic cell models represents a significant roadblock hampering the development of drug-based or cell-based therapies.

The word "otic" refers to the ear. In other words they need to know more about the cells of the inner ear. Their genetic profiles, function, and location within the cochlea. So that they can create a precise model which they can use to create successful therapies. So this part relates to not knowing what is what inside the cochlea. Well, it's not that they don't know, it's that they want to and need to know more to get better results.

This is why they need to find new genetic markers that will help them identify and locate cell types when doing RNA sequencing. They don't have that for all the cell types, which the recent Decibel publication indicates. (They identified many thanks to previous knowledge, but they also had some leftovers they couldn't tell anything about.)

Then you have the problem of targeting specific cells at specific locations. This relates and depends on the cellular models and knowing what is what and where it's at. Next to the first part, I think this will be the hardest.

Then you have the delivery method. You can't easily access the cochlea to deliver the treatment. The only natural way to access the cochlea is through the nose, through the Eustachian tube. But previous attempts to access the cochlea this way for diagnostic purposes proved close to impossible. This was done a couple of years ago. The probe needs to be about 1 mm thick which is a very tiny probe. You need to equip it with jet sprays to clear the way and a light source, and a video lens. This was technically not possible back then, and I don't think it is possible with current technology either. Maybe there will be some innovation that will allow for this in the future, maybe some nano scale lenses and light diodes. But currently, the best way to access the cochlea is through the tympanic membrane.

Whenever you want to access the cochlea with an instrument, you will most likely enter through the tympanic membrane. Then you enter the oval window and deliver the treatment. In case of gene therapy, viral vectors are released and they enter the cells and deliver a copy of the genes they carry into the nuclei. Once inside the nuclei, a promotor is used to initialize the production of proteins that will go on to build the new cells.

Another problem is the viral vectors. They need to be safe for humans. At the same time, they must be able to survive the delivery of the genes or stem cells. The viral vectors function like protective shells. The organ of Corti is submerged in a fluid called the Endolymph. This fluid is toxic, even to the sensory hair cells that live inside it. The hair cells don't normally have contact with this fluid, only their stereocilia bundles do. The cells are underneath, in the epithelial columns of the organ of Corti. Viral vectors carrying genes or stem cells need to reach the epithelium and deliver the payload before Endolymph gets to them. This is part of the success of one viral vector over another. We need to find just the right kind. There is also the endolymphatic sac which has been shown to have immunologic function. The viral vector should not cause immune response in order to survive and deliver the payload.

 

[Reinier]

@Samir
Very interesting read.
I notices also I made a mistake. It is the low-frequencies that have regenerating ability for a short time, like you mentioned.
I understand a lot better what researchers are up against. Quite daunting actually.
Coincidently I read this explanation about the organ of Corti where it shows that there is a length variation according to frequency in outer hair cell length.
http://www.cochlea.eu/en/cochlea/organ-of-corti/variations
So I can understand even better that it is not just regenerating hair-cells, but also there location and therefore speciality. If you regenerate a hair-cell for a high frequency and suppose it locates itself in the low frequency region, the hair-cell will be too short.
Therefore different gene expressions for different locations in the organ of Corty.
Wow...

Also something I wondered about earlier. Why not access the inner ear through the nose?
You explained this quite well. I destill from your explanation that further miniaturisation could be beneficial for future attempts. It is theoretically possible.

 

[Rubenslash]

https://hearinglosscure.stanford.edu/2017/02/sichl-and-the-past-present-and-future/

Update from SICHL.

 

[VRZ78]

how many years? Difficult to tell. Luckily for patients this is not a SICHL exclusive goal. Beside the few research laboratories worldwide focused on finding possible drugs candidates, there are now more than thirty biotech companies some backed up by large pharmaceutical companies who believe that cures for some forms of hearing loss can be found and brought to the market. This is an exciting time

I'd say the probability of hearing loss being solved or in late stage clinical trial in 10 years is quite high. Finger crossed...

 

[Samir]

Very interesting read.

Thank you!

I notices also I made a mistake. It is the low-frequencies that have regenerating ability for a short time, like you mentioned.

Yes, apical means low frequency! Basal means high frequency!

I understand a lot better what researchers are up against. Quite daunting actually.

Coincidently I read this explanation about the organ of Corti where it shows that there is a length variation according to frequency in outer hair cell length.

Yes, length is also a factor. They have a pretty good picture that explains this. I will post it here. Coincidentally, I also discovered this site yesterday. It's a very good and informative site about the cochlea.

So I can understand even better that it is not just regenerating hair-cells, but also there location and therefore speciality.

Yes, it's about:

• Length
• Location
• Form/Arrangement

This is what hair cell stereocilia and their arrangement is supposed to look like:

These are found at the apical portion of the cochlea and they look nice and perfect because those are rarely ever damaged. They are also shorter than those at high frequency sections.

This is what the hair cell stereocilia commonly looks like at the high frequencies:

These are longer than those found at the apical section. But you can tell that they are not meant to look like this. You can see a lot of bent and squashed stereocilia here. It should look more like in the picture above. The formation or arrangement looks good though, since these are natural hair cell sterocilias, not lab regenerated stereocilia.

You can see in the picture here what regenerated cells look like and how they are arranged:
https://www.tinnitustalk.com/threads/anc80-vector-successful-in-penetrating-ohcs.20134/

At the moment, nature does it best!

But you can see now some of the aspects of this daunting hearing restoration task that scientists are up against.

If you regenerate a hair-cell for a high frequency and suppose it locates itself in the low frequency region, the hair-cell will be too short.

No! It will be too tall!

Therefore different gene expressions for different locations in the organ of Corty.

Yes! That's Corti by the way, not... Cortney?...

Corti is named after Alfonso Giacomo Gaspare Corti, an Italian anatomist.

Wow

Agreed!

Also something I wondered about earlier. Why not access the inner ear through the nose?

It has been done for evaluation purposes. I don't have time now to find the paper, but it was done in USA. If not in other places as well. But that paper I read came to the conclusion that the probe had to be very thin, and also the small size of the lens prevented good view, and then you also have the mucus that needs to be cleared away. Also, the patients complained of irritation.

I destill from your explanation that further miniaturisation could be beneficial for future attempts. It is theoretically possible.

Of course! It is possible! It's not a question of if, but when! I mean they already did it before, with inferior technology. It can only get better with time. They also have to make sure the patient is comfortable. So they need to look at that aspect too. Not just miniaturization of instruments.

Precision Optics Corp. is a supplier of miniature lenses for endoscopes, they can make them 0.2 mm in diameter.

We have 25 years experience producing lenses as small as 0.2mm. Our specially trained optics designers and technicians developed new processes and techniques for production of micro lenses. Products and systems requiring optical surfaces <2mm in diameter often result in a tradeoff involving quality, price, or supply. At Precision Optics we can produce lenses to sizes as small as 0.2mm in diameter by using our proprietary micro-precision™ technology with the quality of precision ground and polished lenses approaching the cost of gradient index (GRIN) lenses. New techniques in spinal surgery, neuro surgery, thoracic surgery, cardiac surgery/cardiology, pulmonology, and other specialties demand precise visualization in very small spaces. Precision Optics Corporation can design, develop, and manufacture micro lenses to meet the rapidly increasing demands of minimally invasive/micro surgery or any situation where high quality micro lenses are needed.

http://www.poci.com/micro-optics-components/micro-lenses.php

Also, Micro-LED will be used in future phones in 2018.

https://en.ctimes.com.tw/DispNews.asp?O=HK081ALAMRKSAA00NQ

http://www.ledinside.com/news/2016/11/can_micro_led_challenge_lcd_and_oled_market_position

Maybe one of these can be utilized in endoscopes?

There is also work being done on nano lenses:

Scientists have created the world's thinnest lens, one two-thousandth the thickness of a human hair, opening the door to flexible computer displays and a revolution in miniature cameras. Researchers have said the discovery hinged on the remarkable potential of the molybdenum disulphide crystal.

https://www.sciencedaily.com/releases/2016/03/160311105237.htm

There is also work being done on nano scale diodes within the EU:

http://www.nanodiode.eu/about-nanodiode/

Technology and life sciences go hand in hand. It's usually the technological advancements that allow biologists to enter new areas of study and make new discoveries. At the same time, it makes their work much easier, and allows them to do more work in shorter time when compared to previous protocols and practices used 10 or 20 years ago. It's a constantly accelerating progress all around.

 

[GregCA]

It has been done for evaluation purposes.

It's been done for actual surgery of the middle/inner ear.

 

[RB2014]

https://hearinglosscure.stanford.edu/2017/02/sichl-and-the-past-present-and-future/

Update from SICHL.

This article seems very hopeful. They claim more than 30 biotech companies are working on a cure for hearing loss that believe it can be brought to the market. I think we only know of a small portion of those from everything I have read. Thanks for posting.

 

[Reinier]

No! It will be too tall!

I just recently started this new "hobby/fascination" of mine. I will improve over time
I am already surprised how much I learned about something I did not know anything about almost two years ago.

 

[Samir]

Update from SICHL.

Finally! I have been visiting and revisiting their website quite often recently and never seen any news on their progress. It was about time they posted something.

This article seems very hopeful. They claim more than 30 biotech companies are working on a cure for hearing loss that believe it can be brought to the market. I think we only know of a small portion of those from everything I have read. Thanks for posting.

I know of 11 companies, plus 1 more that has shown interest but may not be working on anything as of yet or they are keeping it a secret.

Of course it can! It will! I am sure it will. It's just a matter of time.

All scientists like to count in tens of years. But it was Stefan Heller who said that they could find a cure for hearing loss in 10 years. This was in 2010. So that would put us at 2020 with some form of cure or treatment of hearing loss. In best case scenario!

Heller writes;

In 2010, I was invited to attend a meeting where Stanford University was trying to define existing challenges in healthcare and how philanthropy might be able to make a difference within a defined time frame. We were split into small groups and each group member was tasked with coming up with a single sentence (less than 25 words) that describes a challenge and offers a solution. Naively, I babbled barely audible, and mainly to myself: "If the University would be able to raise $250 million, we could cure hearing loss in 10 years."

However, they started SICHL only in 2012.

SICHL is celebrating 5 years of collaborative work towards curing inner ear hearing loss, here at Stanford.

That's t - 5 years = 2012.

So, how far have we come in the last five years and where are we going in the next five years? A whole generation of trainees – more than five dozen students, postdocs, and visiting scientists – came through our laboratories working on projects that resulted in more than 130 peer reviewed publications (2012-2016)...

Assuming they didn't start the work until 2012, we could be looking at 2022 as a possible year for a cure. Of course, technology and science is accelerating and new advancements, innovations and discoveries are constantly expanding the bubble of knowledge. This works in our favor.

Also, Stefan Heller was not a freshman when he came to Stanford. He received his PhD in genetics in Germany in 1994 (coincidentally, in the early years of Human Genome Project). He worked at Harvard Medical School before he moved to Stanford in 2005 and started working as director of research at the ENT department. I'm sure he has done some research about the ear even before the idea of an initiative to cure hearing loss came to him at that Stanford meeting in 2010. Otherwise he would not have come up with that idea, had he not seen the need and the possibility of curing hearing loss. It was most likely his current work at the time that sparked the idea. He must have seen that it can be done.

But frankly, I think project was way over his head. Even for someone as well educated and knowledgeable as he was. I think he realized this soon after. That's when you call other people for help! So they have learned a lot since they started, the results speak for themselves. They have also had fruitful collaborations with other scientists around the world. I mentioned earlier the Otostem project. Stanford alone contributed with 680,000 USD in that project.

Although the search for novel drugs is not a trivial endeavor, we are optimistic that first candidates will emerge in future years; how many years? Difficult to tell.
(...)
This is an exciting time, and SICHL supported research will without a doubt play a role in the discovery of novel drugs in future years.
(...)
Finally, a few more comments about how we conduct our research and how research covered by the SICHL initiative will change the world in future years.

I think it's odd how he writes "future years". Instead of writing "coming years". It's funny! It's though as if he wants to set this off in a far, far distant future. It's not just the coming years, it's the future years, or the years of the future. Like... the year of the Robocop! Prime directive: repair cochlear sensor circuitry.

I certainly hope there is not a hidden meaning in that.

 

[Mricha37]

Everyone should be excited. Hope is a powerful mindset that has gotten me through some dark days.

I know all of these regenerative treatments seem far fetched but the fact multiple companies are pushing towards a cure and putting actual funding into it, should be reassuring.

I for one, am SO excited about the next 5 years. Especially if the US government streamlines the regenerative medicine clinical trials. We could be talking years instead of decades!

 

[Samir]

I just recently started this new "hobby/fascination" of mine. I will improve over time

Ey!!!

I am already surprised how much I learned about something I did not know anything about almost two years ago.

Yeah... I wish I knew what I know now 2 to 5 years ago. That might have helped preserve my hearing a lot, and hopefully avoided getting tinnitus. It was in that time frame I was exposing myself to a lot of music listening and other bad habits and doing stupid things.

But hey at least you know now what the dangers are of loud sounds and long exposures. This knowledge may also guide you one day in selecting the most appropriate treatment for yourself. The more you know the better!

I don't trust doctors to think for me and make decisions for me that are in my best interest. The little trust I had in the medical "specialists" is gone. Most of them that I have met don't even show empathy for my case. In any case! Any time! Whatever I have been in for. Now, more often than not, the moment they hear the word "tinnitus" they start looking at the clock on the wall and start rushing me to the door. It's all about saving time and money for them.

I now do my own research and base my decisions on my own conclusions. Tinnitus is also such a weird and stupid condition. It requires multidisciplinary approach like nothing else. Each patient would require a constant contact and follow up with a team of medical workers who are well educated on tinnitus. You would need a team of otologists, audiologists, radiologists, dentists, cardiologists, neurologists, physical therapist, psychotherapists, and maybe a few more.

Here in Sweden, I have to pull all the strings myself! Follow up? What's that??? I don't keep contact with one medical worker, like a local GP, someone who knows my case well. "House doctor" I think it was called in the old days. Not to be confused with Dr. House!

It's supposed to be organized like that though, but it doesn't work like that in practice. It has not worked like that for at least 15 years that I remember of, and I have not been often to the doctor's office, but I remember the days when I could just call in and get an appointment at the local healthcare center the same day, or just walk in and see a doctor if it's something more serious. It used to work like that in the past and it was brilliant. But not anymore! It works only on paper. I won't debate the causes, but the healthcare system is crippled.

I have to beg and beg a nurse to get me a GP meeting! A nurse! In Sweden, a nurse is given more authority over a medical doctor! She gets to decide who needs medical attention and who doesn't. Now get this! You have to call it in over the phone! As if she can tell by your voice and the words you're saying what physical or mental condition you are in.

Internet based video conference would work better!

This is one of those bizarre things about the healthcare system in Sweden that I think many foreigners never heard of. It's so alien! You have to allow time for this idea to sink in. Most countries in Europe don't have this kind of sieving setup.

There is the option to visit the healthcare center in the early morning. You get to meet the nurse. Again! You still have to convince her you need to see a GP. But at least you're having a face to face conversation and she can check your blood pressure and do other basic tests. However, if you get to see a GP, it may not be the same GP you "normally" go to. So you have to explain all over again what you're in for, and he or she needs to learn about your condition through your medical records.

So I have to get past the nurse, see a GP, and beg again for referral to any specialist I might need at the public hospital. If it's something serious they will refer you, no doubt. But many times they don't, even when they should. Lately, in order to put pressure off public hospitals they have started referring people to private clinics, but the state pays for your visit. It's a good time to have a private clinic in Sweden! What kind of healthcare quality you get there depends on the clinic. It's a mixed bag of candy! Some are sweet, some are sour!

I even set my own diagnoses!

In a nutshell I am my own doctor! I have to be when the healthcare system is crippled. I have actually never seen a diagnosis written out on a piece of paper after visiting the local GP, or even one of those specialists they stash up in hospitals. I have never seen a diagnosis written out in Latin, such as tinnitus. They usually explain in simple words what your problem might be, they don't write hard diagnosis like they do in other countries. Not sure what that's about... maybe I'm missing some vital clue.

 

[Reinier]

This knowledge may also guide you one day in selecting the most appropriate treatment for yourself. The more you know the better!

Exactly what I think is another advantage. I hope I, myself (or better understand advice from a specialist) if a future treatment is the one to go for.
I think the GenVec trial is an example. If your hearing loss is profound/severe the early treatments should already be a life changing. When treatments get better, mild to moderate hearing loss may-be treatable. I would like it a lot if I ever need to think about: "Do I wait or do I go"

By the way...when I go to my "house" doctor (also in the Dutch language called like that), a visit is 10 minutes.
If you want a longer visit, the doctor needs to know in advance. This 10 minutes is what the doctor gets paid for by the insurance company.
Insurance companies determine what, if any, treatment you get and which medicine you need. Generic or brand.

 

[Samir]

"Do I wait or do I go"

That's exactly why you need to be well informed. Don't expect these biotech companies to have your best interest in mind. They need someone to test their drugs on so that they may one day make big dollars. So you have to consider carefully what you need, how bad you need it and what they have to offer.

I hear this guy has a cure:

But I don't know if I can trust him! He looks mad!

I know I don't trust this guy!

I think the GenVec trial is an example. If your hearing loss is profound/severe the early treatments should already be a life changing. When treatments get better, mild to moderate hearing loss may-be treatable.

Yes, that's my understanding as well. The CGF166 by GenVec is primarily made for patients with severe to profound hearing loss. Most of the early treatments will be used in this group of patients. Simply because they have the least to lose and most to gain. It's simple logic.

There is also another thing to consider. It's not only about how severe your hearing is. I think it's even more important to know what your bad hearing is caused by. Is it because of loss of hair cells? Or is it because of loss of synapses and spiral ganglion neurons? I think there is too much focus on hair cells alone. Liberman et. al. have shown that survival and regeneration of synapses and spiral ganglion neurons is more important in noise induced hearing loss. How come so few people talk about this? Your new hair cells don't mean anything if you have nothing to connect them to.

By the way...when I go to my "house" doctor (also in the Dutch language called like that), a visit is 10 minutes. If you want a longer visit, the doctor needs to know in advance. This 10 minutes is what the doctor gets paid for by the insurance company. Insurance companies determine what, if any, treatment you get and which medicine you need. Generic or brand.

Can you go to your doctor directly, or do you have to go through the nurse? Can you visit the healthcare center and meet the doctor the same day, or do you have to call it in and get an appointment? I assume that you have to call it in if your visit requires more than 10 minutes. What about people without insurance?

It's interesting to see how healthcare systems work in different countries. I think 10 minutes for a visit is just not enough for even the basic exam. Or they have to work really fast! "Thank you! Come again! Next!"

Do you know if your hearing loss is because of loss of sensory cells or because of loss of synapses? Did you get an OAE and ABR test? Or just the gold standard tone audiogram?

I personally feel like the first thing we should work on is getting a better gold standard diagnostic tools and methods. The OAE and ABR tests are good and necessary tests that complement the audiograms. But here in Sweden they are only used on newborn babies, or if you can't hear sounds at all. Not sure what they expect to find when you can't hear anything... you're essentially deaf. I think they use it in such cases to evaluate outcome of cochlear implants.

Assuming that therapies become available one day to treat hearing loss, one for sensory loss and one for neural loss, you would have to use OAE and ABR in order to tell which one is the best option. You may need both types of treatments, both for sensory and for neural loss.

OAE and ABR are the best diagnostic tools we have at the moment to distinguish sensory from neural damage. There is some excellent work being done on a new OCT diagnostic tool both at Stanford and at Harvard. Dr. Heller mentioned this in the latest blog post on SICHL.

This new tool will be used first on patients that will undergo cochlear implants to gather information about the patient's cochlea in order to optimize the implant procedure. Just like with new drugs being developed, they will use this tool first on those patients that have least to lose and most to gain. Using this tool is minimally invasive as they call it, since they have to enter through the tympanic membrane.

Given some time, I'm sure they will be able to come up with a non-invasive approach for diagnostic only purposes. The natural way of access would be through the Eustachian tube opening. By that time, other imaging technologies may develop to new higher standards that will allow assessment of cochlear cell damage. As of right now no such tool or machine exists. This is one of the reasons we know so little about the cochlea, and why we have to rely on secondary measurements such as audiograms, OAE and ABR to tell us about the cellular state of the cochlea.

 

[Reinier]

Can you go to your doctor directly, or do you have to go through the nurse? Can you visit the healthcare center and meet the doctor the same day, or do you have to call it in and get an appointment? I assume that you have to call it in if your visit requires more than 10 minutes. What about people without insurance?

In general you need to make an appointment. I guess you could call the assistant a nurse? I am not sure, but in the Netherlands we make an appointment with the assistant and not the doctor.
I am sure it is not the same in the whole of the Netherlands. Cities will be different from rural areas. Where I live it is not too bad. Except for the 10 minutes. You can ask for a longer consult in advance though. Insurance is mandatory.
But when you need a specialist the waiting list (in my experience) is absurd long. Sometimes months...

Do you know if your hearing loss is because of loss of sensory cells or because of loss of synapses? Did you get an OAE and ABR test? Or just the gold standard tone audiogram?

If it is NIHL: basic audiogram is all you get.
I guess if the ENT recognises the typical NIHL audiogram a follow up is not needed. For the simple reason that there is no treatment. Inner-ear damage? Learn to live with it
After all the reading I did in the last two years, my diagnosis would be: outer hair-cell loss (60-70dB), neural damage/loss and loss of synapses on inner hair-cells (difficulty decoding sounds that are slightly louder. (starts at ~ 60 dB in regions where I still am able to hear)). I recognise this as distortion. As if an audio compressor is misaligned.
After reading some documents on the possible effects of loss of these synapses, for the higher sound levels on inner hair-cells, I recognised this immediately. You hear it, but are not able to understand. I think many people with inner ear damage recognise this.

There is some excellent work being done on a new OCT diagnostic tool both at Stanford and at Harvard.

Yes I read this too. If we get treatments in the future I think this tool is necessary.

 

[spingee]

http://www.bostonmagazine.com/health/blog/2017/02/21/hearing-loss-treatment/

 

[Samir]

In general you need to make an appointment. I guess you could call the assistant a nurse? I am not sure, but in the Netherlands we make an appointment with the assistant and not the doctor.

I would say that's more like doctor's personal secretary!

It seems to me that it's much easier to get an appointment in Netherlands. This assistant doesn't ask questions, and discourage you from seeing the doctor? She doesn't say things like "Oh you will be fine! Just go home and take an Aspirin!"? If you really want to see the doctor you get to see the doctor, right?

But when you need a specialist the waiting list (in my experience) is absurd long.

So you need referral from a GP/house doctor to see an ENT specialist? How long do you have to wait? Is there a maximum waiting time? In Sweden you have to see a specialist within 3 months, this is regulated by law. If they can't offer you an appointment within that time in your own county/region, they have to send you off to a different hospital in a different county where you will get to see the specialist you need. The same applies to planned surgical operations I believe.

If it is NIHL: basic audiogram is all you get.

Yes, this seems to be the common thread in all such cases from around the world. Some have received OAE and ABR, but it seems to me that these patients are mostly found in USA.

I guess if the ENT recognises the typical NIHL audiogram a follow up is not needed. For the simple reason that there is no treatment. Inner-ear damage? Learn to live with it

Yes, those damn high frequency dips!

I know I had a small dip at 6 kHz in the left ear. One which has improved over the months that followed. But as soon as they saw that dip, disregarding how big it is and the improvement that followed, they proclaimed sensorineural hearing loss! It's like an occupational reflex to them. How do they explain the 15 dB improvement I had? I don't know...

Sometimes I wish I had a perfect audiogram, like in hidden hearing loss. I could then play dumb and tell them that I can't hear a word they're saying. That seems to be the only way to get an OAE or ABR for me. I tried to get those tests in private clinics. I have not found a private clinic that offers these tests. I found one in Finland! But it seems they only do it on babies. In Sweden, these tests are done on babies in hospitals at ENT clinics. They don't do them in private clinics for some reason. I haven't found one. I don't know if it's the cost of equipment or the lack of training in reading the test results, or something else that prevents private practitioners from offering these tests.

Even if there is no treatment available yet, I for one would like to know the cellular state of my inner ears. The OAE and ABR tests can give us some important clues. The more you know the better! This way I can follow my own condition, and should a treatment become available in the future I can know which one will be most appropriate for me. I'm thinking long term, they are thinking short term... it's all about cutting down healthcare costs for the state.

This makes me wonder how GenVec makes the assessment who is best suited for their clinical trial. I don't think they require OAE tests. You probably only need to show an audiogram that indicates severe hearing loss. Which makes me realize the problem they will face in the future.

When GenVec decides to start doing clinical trials on patients with mild or minor hearing loss they will find it difficult to tell who has normal hearing and who does not. In such case they will have to require OAE and maybe ABR test results, or start doing these at their own facilities prior to subjecting patients to drugs that they may or may not need.

After all the reading I did in the last two years, my diagnosis would be: outer hair-cell loss (60-70dB), neural damage/loss and loss of synapses on inner hair-cells (difficulty decoding sounds that are slightly louder. (starts at ~ 60 dB in regions where I still am able to hear)). I recognise this as distortion. As if an audio compressor is misaligned.
After reading some documents on the possible effects of loss of these synapses, for the higher sound levels on inner hair-cells, I recognised this immediately. You hear it, but are not able to understand. I think many people with inner ear damage recognise this.

Yes, this seems like a mix of sensory and neural or synaptic loss.

What I would like to see more than anything is a way to protect the remaining SGN cell bodies while the researchers continue their work on refining the methods for regenerating hair cells. I think neural cells will be much harder to replace or regenerate. Therefore they need to be protected as soon as possible. Thankfully they survive for a long time, up to several years. Liberman et. al. has shown this and it's also evident by the successes in cochlear implant patients. These implants can't work without these neurons. Sadly there is no intervention available in clinics that would protect and prevent further degradation of cells, be it sensory or neural.

 

[Eric Anderson]

What do you guys think about this MIT research?

http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221

It claims it will have human trials in the next 18 months.

 

[Samir]

http://www.bostonmagazine.com/health/blog/2017/02/21/hearing-loss-treatment/

Thanks!

Full report can be found here:
http://www.cell.com/cell-reports/abstract/S2211-1247(17)30136-5

What do you guys think about this MIT research?

http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221

It claims it will have human trials in the next 18 months.

It's the same study that Spingee linked to above.

This is great news!

I really hope it's true that they will start the clinical trials within this time frame. Frequency Therapeutics and Decibel Therapeutics are two of the most prominent biotech companies that seek to cure hearing loss. They are essentially translational platforms for the latest research regarding the inner ear that has been done at some of the top research institutions in the United States.

 

[Aaron123]

What do you guys think about this MIT research?

http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221

It claims it will have human trials in the next 18 months.

To be clear it says they hope to begin trials in 18 months not that they will begin in 18 months. This version is better than the one from bostonmagazine which makes it sound like a cure will be ready for patients in 18 months. That article is almost certainly referring to the goal of starting trials in 18 months. It's still worth remembering the story out of MIT is still effectively a press release.

What I like about this is that it shows the connection between Langer and Karp's work on intestines to the inner ear. I've been wondering how exactly that applies. They also have a cocktail that is much more effective at producing hair cells than existing approaches which should be immediately useful in research. It will be easier to screen drugs, test antibiotics, etc if it is possible to generate large numbers of hair cells.

The results are promising for treatment, but the usual cautions apply. The approach seems to work somewhat for adults, but it works less well than for newborns. They will need good results for primates (safety and efficacy) before trials can begin. Also, the hair cells that they are growing appear to have the properties of functioning hair cells, but they did not test this. (I do like that they generated cells that have OHC characteristics and cells that had IHC characteristics and those appeared to be distinct.)

It will be interesting to see how this affects Audion who I believe are working on small molecule gamma-secretase inhibitor. This seems to be a much more powerful version of that approach. Audion licensed technology resulting from some of Albert Edge's earlier work, and it looks like Frequency will have the option to license this. The licensing could be interesting given that Edge is a founder at Decibel, a competitor of Frequency.

It's also worth noting that the initial submission was received at the end of 2015 so it would be interesting to know how far past this they are at this point.

 

[Reinier]

Sometimes I wish I had a perfect audiogram, like in hidden hearing loss.

Be careful what you which for

 

[Rasmus]

Be careful what you which for

I have Hidden hearing loss sometimes i cant hear where the sound is comming from or what they are saying in a movie because of background noise/music.

 

[Foncky]

What do you guys think about this MIT research?

http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221

It claims it will have human trials in the next 18 months.

Pretty interesting. Things are going fast. They already compare methods to see which one is more efficient. So we're really into the "when will the cure come ?" question, instead of "will the cure come ?".

 

[Christian78]

Pretty interesting. Things are going fast. They already compare methods to see which one is more efficient. So we're really into the "when will the cure come ?" question, instead of "will the cure come ?".

cure for hearing loss not tinnitus, and it is not cure as cure cure something, this is tretment so then they wish for best, and nothing to do with tinnitus

 

[Aaron123]

So we're really into the "when will the cure come ?" question, instead of "will the cure come ?".

We aren't there yet - at least not based on this paper.

 

[Mricha37]

To me, the hardest part has been accomplished by picking a direction to focus on. Now they just have to build onto the theories. I would bet landing on the moon was a bigger challenge conceptually.

The timeline they have chosen is about right for a fast track to clinical trials

 

[Samir]

Be careful what you which for

I agree! It's just frustrating that they won't do more for us, not even in terms of diagnostics. I would want to know the exact cause of my hearing loss, even if there is currently no cure for it.

I have Hidden hearing loss

Have you been to a doctor and he told you this?

You say you "can't hear where the sound is comming from or what they are saying in a movie because of background noise/music." This is what you base your diagnosis on?

See? Why do we have to make our own diagnosis? I thought doctors were supposed to do that for us? Even if they don't have a cure, I would feel better just by knowing what is wrong, what my diagnosis is.

They just say "you have a sensorineural hearing loss". That's at least better than "you have a bad ear". But it's still too unspecific. When a treatment becomes available they will have to do better diagnosis than that. They can't just give you drugs for unspecific indications in good hopes that it will work. We can do very well on our own, by doing things like drugging ourselves with Trobalt in good hopes that it will have an affect on tinnitus.

Well... is it sensory or is it neural damage? They can't tell, or rather they won't tell because they don't want to waste any more time and money on you, since you're out of luck anyway. That's their way of thinking. They could do the OAE and ABR. But they preserve that for babies, and for those that are nearly deaf and will get a cochlear implant. I think they should do OAE and/or ABR on everyone that they find to have sensorineural hearing loss, to further distill the exact diagnosis.

On me, they didn't even bother to check for other causes of tinnitus other than hearing loss. There are a number of different causes of tinnitus. They were like, "Ah! The high frequency dip!" They suddenly knew it all just by looking at the audiogram. No need for further investigation they say. They didn't check for TMJ, didn't ask me what kind of sound I hear, didn't do CT scan, didn't check for acoustic neuroma, they didn't ask me about my mental and physical state.

I called in a week later and told them about that sharp clicking sound I had been hearing long before I developed or became aware of the constant ringing sound. Now all of a sudden they are concerned that it might be something with the ossicular chain and want me to come back to the clinic to do a reflex test. They could have asked about what sounds I was hearing the last time I was at the clinic... now I have to wait to get back to them.

This just sucks... The doctor used me like a human model to educate the intern that was present at the last appointment to explain to him what muscle was situated where and what cranial nerve controlled what, instead of spending more of the time talking with me, and asking me important questions and explaining the previous test results in more detail.

 

[Samir]

cure for hearing loss not tinnitus

I fear that you might be right! They are all just hypothesizing. The main focus is on curing hearing loss, which if they are right may cure tinnitus.

and it is not cure as cure cure something, this is tretment so then they wish for best, and nothing to do with tinnitus

Again, they are hoping it will cure tinnitus if they can cure hearing loss. Curing tinnitus in the process is considered to be like a bonus. They don't really fully understand tinnitus. They don't even have a diagnostic method for detecting tinnitus in humans objectively. They have used some behavioral tests in animal models which they say provides them with a way to detect tinnitus in animals.

I think a cure for hearing loss will become available in a few years time, and I believe there is a good chance for great outcome. But there is still a lot of work to be done in a lot of areas. First and foremost in diagnosing sensorineural loss. If the treatment is made for sensory hair cell loss, but your hearing loss is due to synaptopathy then I'm afraid the treatment will be fruitless. It will require one additional treatment, that for synaptogenesis.

Curing hearing loss may help cure tinnitus. But that may only be true in tinnitus caused by hearing loss. There seems to be an overwhelming consensus that all forms of tinnitus ultimately stem from hearing loss, and that other indications that tinnitus may have other causes as well is just bad data.

 

[Samir]

Who is working on curing TTTS and ASD? These are often linked to patients who have hearing loss caused by acoustic shock or trauma, many of whom also have T and H. I am waiting and hoping that the work currently being done to cure sensorineural hearing loss will lead to curing tinnitus. But do I have reason to hope that this will bring my TTTS and ASD to rest? I think this might require some more work to be done in the field of neuroscience.

 

[Rasmus]

I agree! It's just frustrating that they won't do more for us, not even in terms of diagnostics. I would want to know the exact cause of my hearing loss, even if there is currently no cure for it.


Have you been to a doctor and he told you this?

You say you "can't hear where the sound is comming from or what they are saying in a movie because of background noise/music." This is what you base your diagnosis on?

See? Why do we have to make our own diagnosis? I thought doctors were supposed to do that for us? Even if they don't have a cure, I would feel better just by knowing what is wrong, what my diagnosis is.

They just say "you have a sensorineural hearing loss". That's at least better than "you have a bad ear". But it's still too unspecific. When a treatment becomes available they will have to do better diagnosis than that. They can't just give you drugs for unspecific indications in good hopes that it will work. We can do very well on our own, by doing things like drugging ourselves with Trobalt in good hopes that it will have an affect on tinnitus.

Well... is it sensory or is it neural damage? They can't tell, or rather they won't tell because they don't want to waste any more time and money on you, since you're out of luck anyway. That's their way of thinking. They could do the OAE and ABR. But they preserve that for babies, and for those that are nearly deaf and will get a cochlear implant. I think they should do OAE and/or ABR on everyone that they find to have sensorineural hearing loss, to further distill the exact diagnosis.

On me, they didn't even bother to check for other causes of tinnitus other than hearing loss. There are a number of different causes of tinnitus. They were like, "Ah! The high frequency dip!" They suddenly knew it all just by looking at the audiogram. No need for further investigation they say. They didn't check for TMJ, didn't ask me what kind of sound I hear, didn't do CT scan, didn't check for acoustic neuroma, they didn't ask me about my mental and physical state.

I called in a week later and told them about that sharp clicking sound I had been hearing long before I developed or became aware of the constant ringing sound. Now all of a sudden they are concerned that it might be something with the ossicular chain and want me to come back to the clinic to do a reflex test. They could have asked about what sounds I was hearing the last time I was at the clinic... now I have to wait to get back to them.

This just sucks... The doctor used me like a human model to educate the intern that was present at the last appointment to explain to him what muscle was situated where and what cranial nerve controlled what, instead of spending more of the time talking with me, and asking me important questions and explaining the previous test results in more detail.

Im 99% sure i have hidden hearing loss because i have all the bad parts of hidden hearing loss that i have reading on the internet(i know this sounds confusing sorry bad english) I have read that you get hidden hearing loss for using headset alot and i have been using headset for 10+ years alsmost everyday. I have been testet and they told me i have no hearing loss but i still have a hard time hearing what people are telling and if there is some kind of background noise and i try to listing to what people says it just sounds like nonsense :/

The only thing MY ENT were checking was for hearing loss and presure in my ears, and everything was fine And i still have Loud T that i can hear even when im driving in a car and it sounds like someone whistle in my ears really loud if there is no sounds around. Personly i dont really care about my hidden hearing loss (atleast i dont care about it right now but i will mostlikely in the future when it get worse) i just want T gone.

 

[Samir]

Im 99% sure i have hidden hearing loss because i have all the bad parts of hidden hearing loss that i have reading on the internet

(...)

i still have a hard time hearing what people are telling and if there is some kind of background noise and i try to listing to what people says it just sounds like nonsense :/

My understanding 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...

I have been testet and they told me i have no hearing loss

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.