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Prof. Thanos Tzounopoulos Receives $2 Million Grant

Anyone else think it's a weird coincidence that Knopp Biosciences is in pre-clinical for a tinnitus drug using the same potassium ion channel receptor as Dr. Tzounopoulos while also being in the same city as him? He's not listed on their webpage but I do wonder...
I saw that before and checked the exact same thing, I couldn't find a connection between them either.
 

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So I came across this paper tonight from 2016 by a researcher from Johns Hopkins which discusses the role of the Type 2 nerve fibers as pain receptors in the cochlea, which, as we've come to learn in recent years, could point to the pathology underlying pain hyperacusis. An interesting snippet from the abstract:

"Exposure to the KCNQ channel activator retigabine suppressed the type 2 fiber's response to hair cell damage. Type 2 afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear."

Interesting, perhaps suggesting that retigabine could be a potential therapy for pain hyperacusis?
https://jscholarship.library.jhu.edu/handle/1774.2/40719
 

Very encouraging! I wonder if the development of this drug could also potentially target hyperacusis as well as T given that there was a paper showing that retigabine suppressed the type 2 nerve fibers' (pain fibers) response. And it looks like they're trying to reformulate it so it's more effective and carries fewer side effects.

Good symposium lineup too
 
This drug is currently in preclinical test. Does somebody know when first results of this test can be expected?
 
Received this message from Dr Thanos today (15 March, 2020)

I am very sorry to learn of your tinnitus


Regarding our efforts: We currently perform preclinical studies, including toxicology, pharmacokinetics, metabolism etc.

We are encouraged by our research results so far

We expect to launch a clinical trial once preclinical studies are successfully completed

Unable predict the exact timeline – but we are committed it.


Thank you for your kind word and encouragement
 
Received this message from Dr Thanos today (15 March, 2020)

I am very sorry to learn of your tinnitus

Regarding our efforts: We currently perform preclinical studies, including toxicology, pharmacokinetics, metabolism etc.

We are encouraged by our research results so far

We expect to launch a clinical trial once preclinical studies are successfully completed

Unable predict the exact timeline – but we are committed it.

Thank you for your kind word and encouragement
Thanks for the update. Probably this is one of the more promising drugs as Trobalt has already shown to quieten tinnitus. But hopefully Dr. Thanos's drug has not the same side effects as Trobalt: Blue skin, impairment of vision, ...
 
Thanks for the update. Probably this is one of the more promising drugs as Trobalt has already shown to quieten tinnitus. But hopefully Dr. Thanos's drug has not the same side effects as Trobalt: Blue skin, impairment of vision, ...
Isn't there a new improved version of Trobalt in development?
 
Tomorrow (30 April 2020 at 12 noon Eastern Time US / Canada) Professor Tzounopoulos will host a Zoom webinar with updates on his research.

The link to register:

https://zoom.us/webinar/register/WN_u9Nx0NtJRMm8Ofw68SsVDQ
Thanks for the info. I registered for tomorrow's webinar and send them these questions
  • When are clinical trials expected to start?
  • Is RL-81 also supposed to help pain hyperacusis?
  • Since RL-81 is a reformulation of Trobalt, what is done to prevent that it does not have the same side effects?
Let's see what Dr. Tzounopoulos says.
 
I had some trouble understanding parts of this since there were no captions but what I gathered:

--Clinical trials are coming within the next year and a half.

--Some (or all?) will be in Australia. Anyone understand this better?

--This is just a personal annoyance but some researchers don't appear know the difference between loudness hyperacusis and noxacusis or didn't appear to understand the question in the Q and A very well. Dr. Tzounopoulos expressed that he wants to study hyperacusis, too, but it wasn't clear if they understood the question in regards to "pain hyperacusis" or if he meant loudness.

--Dr. Tzounopoulos mentioned that tinnitus is due to cochlea injury in the vast majority of people (Schizophrenia related hearing disorders were listed as an exception that occurs with possibly a direct insult to the brain first). His method seeks to normalize the brain's response to that damage by modulating potassium ion channels. The theory is that opening these channels will make the brain match the lack of input after damage with the brain's "prediction" (which is a normal brain function that is being hampered by cochlear damage).

--Dr. Tzounopoulos does not think the pill would have to be taken indefinitely.

--It appears they want to test on more recent tinnitus first (eg. 6 months) because they already know from rodents they can prevent tinnitus from becoming permanent but they hope to eventually extend out the time frame.

--They are very concerned with making sure their drug is much less toxic that Trobalt.

Did I get anything wrong? Miss anything important?
 
I had some trouble understanding parts of this since there were no captions but what I gathered:

--Clinical trials are coming within the next year and a half.

--Some (or all?) will be in Australia. Anyone understand this better?

--This is just a personal annoyance but some researchers don't appear know the difference between loudness hyperacusis and noxacusis or didn't appear to understand the question in the Q and A very well. Dr. Tzounopoulos expressed that he wants to study hyperacusis, too, but it wasn't clear if they understood the question in regards to "pain hyperacusis" or if he meant loudness.

--Dr. Tzounopoulos mentioned that tinnitus is due to cochlea injury in the vast majority of people (Schizophrenia related hearing disorders were listed as an exception that occurs with possibly a direct insult to the brain first). His method seeks to normalize the brain's response to that damage by modulating potassium ion channels. The theory is that opening these channels will make the brain match the lack of input after damage with the brain's "prediction" (which is a normal brain function that is being hampered by cochlear damage).

--Dr. Tzounopoulos does not think the pill would have to be taken indefinitely.

--It appears they want to test on more recent tinnitus first (eg. 6 months) because they already know from rodents they can prevent tinnitus from becoming permanent but they hope to eventually extend out the time frame.

--They are very concerned with making sure their drug is much less toxic that Trobalt.

Did I get anything wrong? Miss anything important?
Clinical trials in Australia. That's shocking. I wouldn't have expected they would do clinical trials there. I wonder why they would choose to do clinical trials there and not USA.
 
--Dr. Tzounopoulos does not think the pill would have to be taken indefinitely.
Just wanted to add that I believe he said they used a twice a day dosing schedule for only 2 days and it worked even 4 weeks after onset. But hopefully someone can confirm.

Even if their final dosing ends up being longer I don't think we'll be looking at the multi-month dosing regiments that people were experimenting with when it came to Trobalt.
 
--Dr. Tzounopoulos mentioned that tinnitus is due to cochlea injury in the vast majority of people (Schizophrenia related hearing disorders were listed as an exception that occurs with possibly a direct insult to the brain first). His method seeks to normalize the brain's response to that damage by modulating potassium ion channels. The theory is that opening these channels will make the brain match the lack of input after damage with the brain's "prediction" (which is a normal brain function that is being hampered by cochlear damage).
I wonder what this means for other causes. Obviously treating underlying conditions is the first route to go down, but if that doesn't work (eg brains not adjusting accordingly anymore), how effective would it be?

Or, those with damage elsewhere in their ears? If it's targeting the brain's abnormal response to (any) damage within the auditory pathway, I hope it works for those without clear cochlear injuries too...

But time will tell. I do hope it'll be available and effective to those with chronic tinnitus too.
 
I wonder what this means for other causes. Obviously treating underlying conditions is the first route to go down, but if that doesn't work (eg brains not adjusting accordingly anymore), how effective would it be?

Or, those with damage elsewhere in their ears? If it's targeting the brain's abnormal response to (any) damage within the auditory pathway, I hope it works for those without clear cochlear injuries too...

But time will tell. I do hope it'll be available and effective to those with chronic tinnitus too.
Unless you have TMJ or a head injury, you likely do in fact have cochlear damage that doesn't show up on a standard audiogram.
 
Unless you have TMJ or a head injury, you likely do in fact have cochlear damage that doesn't show up on a standard audiogram.
I do have a neck injury and some sinus issues going on but I don't completely rule out noise/cochlear damage.
 
I do have a neck injury and some sinus issues going on but I don't completely rule out noise/cochlear damage.
The good news is better diagnostics tools are on the horizon. Harvard (https://stankovic.hms.harvard.edu/optical-imaging-inner-ear) and another Ivy League - who escapes me at the moment - are both working diligently to address this.

I think 10-15 years people will be getting inner ear images routinely the same way we now get MRIs and CT scans.
 

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