Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Why not develop an approach on ex vivo cochlea. It is not yet finalized but it could be a more ethical approach towards animals and more convincing results.
An ex vivo cochlea is a better place to start for sure. But you still need to test for systemic effects. But I agree it would be better to start with expanded tissues or cell cultures first and often that's how it is done.
 
Well of course. If only more ENTs would update their knowledge on this!

I know right!?

I've added the audiogram of my tinnitus ear. When I went to see the ENT, I first saw an ENT in training who prescribed an extended audiogram. The results are quite obvious. When she went to consult with the head of the ENT department (a professor doctor nonetheless),the response of the prof was that it's useless to do an extended audiogram, because there's no literature on it's relation to tinnitus. Just another example of how much your average ENT cares about tinnitus..
 

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I know right!?

I've added the audiogram of my tinnitus ear. When I went to see the ENT, I first saw an ENT in training who prescribed an extended audiogram. The results are quite obvious. When she went to consult with the head of the ENT department (a professor doctor nonetheless),the response of the prof was that it's useless to do an extended audiogram, because there's no literature on it's relation to tinnitus. Just another example of how much your average ENT cares about tinnitus..
Oh wow! That is crazy. I had a similar encounter yesterday. I planned to remove my earwax. This time not my usual ENT (who is really good and understanding) removed it, but a different one. We discussed tinnitus briefly. I told him my hearing looks fairly normal on a 8kHz audiogram. He then immediately starting talking that tinnitus can also arise from other things than noise trauma. He didn't even consider that the higher frequencies needs to be tested or can be the cause of it.

Nonetheless, my audiogram looks similar to yours until the 8kHz. I planned my extended audiogram to see how my hearing is from 8kHz to 20kHz. Let's see.
 
I'm willing to bet that there would be many human volunteers.

And many who would regret volunteering afterwards. Even drugs that have gone through animal testing can cause horrible side effects, ranging from losing limbs to developing rate auto immune diseases. Take for example trobalt, which led to people turning blue, getting VS,... and this was a drug that webt through all the trials. There is a reason pharma pays big bucks for people participating to drug trials.
 
Like tinnitus, for example.

Wtf. Really?

Turning blue might be a bit of an exaggeration, but there are multiple reports of people having skin discoloration and retinal pigment abnormalities. To be honest if that would have been the only side effect and it would cure my tinnitus, I would have been running around like Papa Smurf by now :hungry:.
 
And many who would regret volunteering afterwards. Even drugs that have gone through animal testing can cause horrible side effects, ranging from losing limbs to developing rate auto immune diseases. Take for example trobalt, which led to people turning blue, getting VS,... and this was a drug that webt through all the trials. There is a reason pharma pays big bucks for people participating to drug trials.

What does VS stand for?
 
And many who would regret volunteering afterwards. Even drugs that have gone through animal testing can cause horrible side effects, ranging from losing limbs to developing rate auto immune diseases. Take for example trobalt, which led to people turning blue, getting VS,... and this was a drug that webt through all the trials. There is a reason pharma pays big bucks for people participating to drug trials.
Not to mention maybe even make their tinnitus worse. Not a chance in hell I will try it unless they've got sound science backing it before.
 
https://journalotohns.biomedcentral.com/articles/10.1186/s40463-020-00432-7

Brain-derived nerve growth factor in the cochlea - a reproducibility study
Conclusion
Our original finding that Intracochlear BDNF can improve hearing in guinea pigs was confirmed, but the improvement demonstrated by the methods in this paper is too small for clinical application.

So then this means the outlook for OTO-413 is not very good. Maybe they better should have tested how this BNDF affects tinnitus & hyperacusis.
 
Conclusion
Our original finding that Intracochlear BDNF can improve hearing in guinea pigs was confirmed, but the improvement demonstrated by the methods in this paper is too small for clinical application.

So then this means the outlook for OTO-413 is not very good. Maybe they better should have tested how this BNDF affects tinnitus & hyperacusis.
The study also says:

"Perhaps multiple applications, a different dose or other method would show more response. We plan to pursue a multiple dose regimen in future work."

Another interesting point is that they saw hearing improvement in the entire range of hearing.

Besides, isn't OTO-413 for hidden hearing loss instead of sensorineural hearing loss?
 
The study also says:

"Perhaps multiple applications, a different dose or other method would show more response. We plan to pursue a multiple dose regimen in future work."

Another interesting point is that they saw hearing improvement in the entire range of hearing.

Besides, isn't OTO-413 for hidden hearing loss instead of sensorineural hearing loss?
When this BNDF gives enough hearing improvement to quieten noise induced tinnitus to some extent then this should definitely be further investigated. If this works across the whole frequency range, this would be even better. Since FX-322 so far as I understood works only in the high frequencies.
 
Conclusion
Our original finding that Intracochlear BDNF can improve hearing in guinea pigs was confirmed, but the improvement demonstrated by the methods in this paper is too small for clinical application.

So then this means the outlook for OTO-413 is not very good. Maybe they better should have tested how this BNDF affects tinnitus & hyperacusis.
Hidden hearing loss is called that because it doesn't affect your audiogram. It only makes sense they didn't see an improvement. Hair cells affect pure tone, synapses affect things like speech in noise, which can't be measured in animals.

BDNF is for synaptopathy.
 
Perhaps hope on the horizon for those who have a lack of supporting cells in damaged areas of the cochlea, hopefully even for those with flat epithelia (profound hearing loss):

Title:
Microenvironment Can Induce Development of Auditory Progenitor Cells from Human Gingival Mesenchymal Stem Cells

''Here, we report the potential of GMSCs (gingival mesenchymal stem cells) to differentiate into auditory progenitor cells while supporting them with an optimized three-dimensional scaffold and certain growth factors (......) Our in vitro and in vivo studies confirmed the auditory differentiation potential of GMSCs within the engineered microenvironment''

Link: https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.9b01795
 
Perhaps hope on the horizon for those who have a lack of supporting cells in damaged areas of the cochlea, hopefully even for those with flat epithelia (profound hearing loss):

Title:
Microenvironment Can Induce Development of Auditory Progenitor Cells from Human Gingival Mesenchymal Stem Cells

''Here, we report the potential of GMSCs (gingival mesenchymal stem cells) to differentiate into auditory progenitor cells while supporting them with an optimized three-dimensional scaffold and certain growth factors (......) Our in vitro and in vivo studies confirmed the auditory differentiation potential of GMSCs within the engineered microenvironment''

Link: https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.9b01795
The researcher I spoke to thought it was a solvable problem for even those with flat epithelial but her time line (15-20 years) was discouraging :(.
 
The researcher I spoke to thought it was a solvable problem for even those with flat epithelial but her time line (15-20 years) was discouraging :(.
@FGG I don't think the time line is set in stone. And with the plans to reduce bureaucratic procedures at the FDA, it may help speed up the process for you and other tinnitus sufferers.
 

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