Prof. Thanos Tzounopoulos Receives $2 Million Grant

Discussion in 'Research News' started by Jack Straw, Dec 4, 2018.

    1. Flyingsheep
      Sheepish

      Flyingsheep Member

      Location:
      Cleveland, OH
      Tinnitus Since:
      09/2018
      Cause of Tinnitus:
      Unknown
      I'm also just making a wild guess based on how many people have reported developing VS after getting eye floaters. Why do they? Who knows, maybe there is some kind of dysfunction with the brain adapting and trying to filter out floaters? I have floaters and don't have VS (from what I can tell) except I notice grainy-like dots in complete darkness, but I've noticed that since I was a kid and thought it was normal.
       
    2. Croaker
      Haunting

      Croaker Member

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Unknown
      While exploring other organizations researching Kv7 modulators, I found Knopp Biosciences. They’ve been discussed on Tinnitus Talk before, and they haven’t had an official press release since December.

      However, I thought I would still make this post because their pipeline shows they are exploring potassium channels not only for epilepsy and tinnitus, but neuropathic pain as well. This lends further credence to the idea that this class of drugs will address pain hyperacusis beyond anecdotal reports about Trobalt. Unfortunately they are only at the preclinical stage but it is still very interesting to me.

      https://knoppbio.com/pipeline
       
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    3. Lucifer

      Lucifer Member Podcast Patron Benefactor

      Tinnitus Since:
      2017
      Cause of Tinnitus:
      Ear Infection
      If Xenon Pharma drug does not work for pain hyperacusis at least we still have FX-322 and Dr Thanos' drug to come out.

      So many different drugs in the making. Hoping that for almost all of us FX-322 should allow us to resume our lives.
       
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    4. Alex0o_o0
      Confused

      Alex0o_o0 Member Benefactor

      Location:
      Belgium
      Tinnitus Since:
      01/10/2018 - 04/04/2020
      Cause of Tinnitus:
      Whiplash/concussion - Sound trauma
      Hi All,

      As far as I can find the only research that is being done for Kv7 modulators is as a treatment of tinnitus caused by NIHL. Does anyone know whether it could also be effective for tinnitus triggered by other causes?
       
    5. Christiaan
      Vegged out

      Christiaan Member Podcast Patron Benefactor

      Location:
      The Hague, the Netherlands
      Tinnitus Since:
      2016
      Cause of Tinnitus:
      Bloody headphones in 2016,worsened in 2020
      Hi @Alex0o_o0, I'm not a doctor or even a specialist in that area, but my guess is that the pill may also help those who do have another cause than NIHL, such as ototoxic medicine or infections. Danny Boy (infection) & ATEOS (ototoxic/head injury/infection) were one of those who reported benefit from Trobalt, a drug that is a precursor to Dr. Tzounopoulos' RL-81. I hope that it also works for you.
       
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    6. Flyingsheep
      Sheepish

      Flyingsheep Member

      Location:
      Cleveland, OH
      Tinnitus Since:
      09/2018
      Cause of Tinnitus:
      Unknown
      Agreed, especially my case since my tinnitus does not appear to be from noise trauma. If taking Clonazepam has shown a reduction in tinnitus for me (despite causing a huge spike later) does anyone think that is a sign that this drug could potentially be effective as well?
       
      • Good Question Good Question x 1
    7. Amv

      Amv Member

      Tinnitus Since:
      16/7/2017
      Cause of Tinnitus:
      -
      Thanos is an awesome researcher, he and his team have all my support. Thanks for being dedicated to tinnitus!
       
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    8. Alue
      No Mood

      Alue Member

      Tinnitus Since:
      01/2016
      Cause of Tinnitus:
      Acoustic Trauma
      I have loud intrusive multi tone tinnitus. I can hear it in the shower.
      I'm not sure I can describe it, I was fairly new to tinnitus and it was a big relief.
      That's too bad. I did occasionally experience some mild visual symptoms at the higher doses, but they were only temporary for me; I know some people here had much more persistent and severe side effects from the drug. I had an ophthalmologist monitor my eyes for any changes and had none while on the drug. Had it not been for GSK pulling it from the market, I would have been very tempted to keep taking it.

      I did have a bottle leftover, but I don't think it is good anymore as I accidentally left it in an area of high heat for too long.
       
    9. Joly

      Joly Member

      Tinnitus Since:
      22/08/2019
      Cause of Tinnitus:
      Traumatisme sonore
      On Tinnitus Talk, we all have different tinnitus (intensity and sound). How with the same dosage of this drug it will affect us? Will some people need to take more medication than others?
       
      • Good Question Good Question x 3
    10. vermillion
      No Mood

      vermillion Member Benefactor

      Tinnitus Since:
      12/2016
      Cause of Tinnitus:
      Bad luck
      How many degrees? Do you also have hyperacusis?
      Sorry, I think I am getting off topic. You can PM me @Alue.
       
    11. vermillion
      No Mood

      vermillion Member Benefactor

      Tinnitus Since:
      12/2016
      Cause of Tinnitus:
      Bad luck
      Dosage?
       
    12. Mentos

      Mentos Member Benefactor

      Location:
      Cracow, Poland
      Tinnitus Since:
      03/2015
      Cause of Tinnitus:
      Noise induced, loud rock concert
      300mg a day.
       
    13. vermillion
      No Mood

      vermillion Member Benefactor

      Tinnitus Since:
      12/2016
      Cause of Tinnitus:
      Bad luck
      Indeed that is a dosage that could provide a therapeutic effect, however for each person it differs. It would have been interesting back then to have tried to increase it and check whether it could make any difference. After all the maximal dose was supposed to be 1200mg. Anyway... Trobalt was not the tinnitus panacea either way.
       
    14. serendipity1996

      serendipity1996 Member Podcast Patron

      Tinnitus Since:
      2011
      Cause of Tinnitus:
      Unknown but suspect noise-induced
      Update: I have received a reply from Paul Fuchs! I thought it would be appropriate to post the reply I received here since it pertains more to Retigabine. He replied really promptly and gave quite a lengthy response - he's also taken note of Retigabine as a potential therapy. Also great to hear that there is an ongoing doctoral thesis on this.


      "Thanks for your note, but most sorry to know you are among those suffering from these paradoxical ear pathologies. I'm not a physician so please take what follows as informational only, not prescriptive.

      As I'm sure you're aware from your research, tinnitus and hyperacusis both follow some degree of peripheral damage. Tinnitus is complicated by central nervous system changes, but hyperacusis in particular seems more akin to peripheral somatic neuropathies. We have been struck by the potential of potassium channel openers to diminish the excitability of type 2 cochlear afferents, putative damage sensors, and have been told about retigabine use by by some. Our work to date has only involved cochlear tissue excised from rats or mice. Our next steps are to employ genetically-modified mice in which type 2 cochlear afferents can be selectively modulated by systemic drug delivery. We need this experimental model to determine whether type 2 cochlear afferents really act as nociceptors. So for example, we would 'chemogenetically' activate type 2 cochlear afferents to evoke avoidance behavior, then treat with retigabine or other drugs to see if effective. Other avenues include the use of magnetic nanoparticles for drug delivery specifically to the inner ear (avoiding systemic effects).

      So in short, yes, we will continue our efforts to develop informative animal models in which to test hypotheses of disease, and potential therapies. We've spent some years now pursuing the idea that type 2 cochlear afferents are nociceptors responsible for 'noxacusis', painful hyperacusis. We speculate that these neurons and/or the surrounding tissue, become hyperexcitable after peripheral trauma (ongoing doctoral thesis of Nate Nowak), by analogy to the hyperalgesia of somatosensory afferents. Postdoctoral fellow Dr. Megan Wood is exploring the impact of cochlear inflammation and type 2 activity as additional factors in the prolonged pain response to sound."
       
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    15. Alue
      No Mood

      Alue Member

      Tinnitus Since:
      01/2016
      Cause of Tinnitus:
      Acoustic Trauma
      I think it was like 115F (46C) for 24+ hours. Long story short I had water damage in my bathroom and had a large industrial dehumidifier running in it to get rid of the moisture. I forgot that I had medications in my medicine cabinet in the bathroom. :banghead:

      I do have hyperacusis and reactive T, it's mostly the loudness kind, but I do get pain if things get loud enough. For me the pain threshold is much higher than the loudness threshold (which is pretty low).
       
    16. Croaker
      Haunting

      Croaker Member

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Unknown
      Good to see he thinks the potassium channel drugs have a decent chance of addressing the problem. Sounds like he and his associates are many years from directly producing anything useful though. I wonder if it would be worth contacting Nate Nowak or Megan Wood? Perhaps in future communication we could see what he thinks of nav 1.7 inhibitors?
       
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    17. serendipity1996

      serendipity1996 Member Podcast Patron

      Tinnitus Since:
      2011
      Cause of Tinnitus:
      Unknown but suspect noise-induced
      True. I think there's still a lot to uncover to determine and prove exactly what the underlying mechanisms are but it's encouraging nonetheless that we already have a new retigabine in clinical trials (Xenon's version) at least and we have some anecdotal evidence that it has helped people.
       
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    18. Mentos

      Mentos Member Benefactor

      Location:
      Cracow, Poland
      Tinnitus Since:
      03/2015
      Cause of Tinnitus:
      Noise induced, loud rock concert
      I just listened to the Tinnitus Talk Podcast with Thanos Tzounopoulos. Did any of you know he has tinnitus himself? He said he's had it for 5 years already. I was shocked, he seems not to be bothered by it at all as he spoke. Maybe this will be a driver for him to push the research forward.
       
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    19. lymebite
      Vegged out

      lymebite Member Podcast Patron Benefactor

      Location:
      United States
      Tinnitus Since:
      2013
      Cause of Tinnitus:
      Unknown
      The presentation by Dr. Tzounopoulos is now available on YouTube with subtitles:

      Sounds + Sound Bites: Tinnitus, Hearing Loss, and Drug Discovery

      Sounds + Sound Bites: Tinnitus, Hearing Loss,...
       
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    20. Nobody19

      Nobody19 Member Podcast Patron Benefactor

      Tinnitus Since:
      2012
      Cause of Tinnitus:
      Clubbing
      Lots of people (including me) aren't very bothered by their tinnitus.
       
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    21. UKBloke

      UKBloke Member Podcast Patron Benefactor

      Tinnitus Since:
      1991
      Cause of Tinnitus:
      Loud Music / family history
      Thanks for posting this.

      As someone with chronic tinnitus I often listen out for any comment about, acute vs. chronic, tinnitus researchers make in order to try and gauge their focus. Regarding this point, Prof. Tzounopoulos made a rather curious remark. Around 46:20, one of the audience asks; will the drug have to be taken for the life of the patient in order to cure or reduce tinnitus, or will it work with a specific set of doses?

      Prof. Tzounopoulos responds by talking about dosing mice but importantly goes on to state: [my emphasis] "I don't expect it to be taken every single time. It should be a critical window that we have not fully determined yet that when you take it can prevent the development of the disorder."

      It may be because English is not his native language, however, his statement, if taken literally, raises a number of questions. Who would take a tablet to prevent tinnitus developing? I can't imagine that. Therefore would his statement have been more accurate if he'd said, prevent the development of chronic tinnitus? If that is the case, however, how is he making the distinction between acute and chronic tinnitus? I'm not aware that medicine in general has been able to agree on that distinction yet. If he is really only dealing with acute tinnitus, (and perhaps we'll be able to determine this by the human trial recruitment criteria) then I think that is disappointing and for sure any eventual drug will be of no interest to me.

      What do you guys make of his comment? Perhaps I need to email him direct for some clarification.
       
      • Good Question Good Question x 3
    22. Croaker
      Haunting

      Croaker Member

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Unknown
      You should read the Tinnitus Talk Podcast transcript and look into how these potassium channels drugs work. It won’t be limited to acute.
       
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    23. UKBloke

      UKBloke Member Podcast Patron Benefactor

      Tinnitus Since:
      1991
      Cause of Tinnitus:
      Loud Music / family history
      Yea I'd listened to the Tinnitus Talk Podcast and was quite satisfied that treatment wouldn't be limited to acute stage, but when I heard the other interview posted here in the thread I wasn't so sure. I've now actually written directly to Prof. Tzounopoulos, and if I get a reply I'll drop a note of it in here.
       
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    24. Mentos

      Mentos Member Benefactor

      Location:
      Cracow, Poland
      Tinnitus Since:
      03/2015
      Cause of Tinnitus:
      Noise induced, loud rock concert
      But not all of them are famous researchers, tinnitus for sure does not help to have clear mind.
       
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    25. Christiaan
      Vegged out

      Christiaan Member Podcast Patron Benefactor

      Location:
      The Hague, the Netherlands
      Tinnitus Since:
      2016
      Cause of Tinnitus:
      Bloody headphones in 2016,worsened in 2020
      Small update: a new, yet a bit of a cryptic reply by dr. Tzounopoulos about whether or not potassium channels are damaged after noised-induced hearing loss. Maybe somebody else can mail him about. It's still not very clear why it is a possibility that there's no potassium channel in a neuron.
      _______________________________________________________________________________
      Mail:
      Dear Dr. Tzounopoulos,


      Thank you very much for partaking in the Tinnitus Talk podcast. The interview was very insightful, but foremostly hopeful. Thank you for giving people like me hope.

      However, I hope you don't mind me asking a small question about the potassium channels. You've mentioned in the interview that one of the possibilities why a potassium channel is not working, is that the channel might not make it to the membrane after acoustic damage. Does this mean that the RL-81 pill might not work for those whose potassium channels are damaged? I've also an additional question: how can we know if the potassium channels are damaged?

      With kind regards,

      Christiaan van R.

      _______________________________________________________________________________
      Answer:
      We can’t measure potassium channel activity in humans

      If potassium channels are not in the plasma membrane, RL-81 would not work

      In mice, after noise trauma, the channels are in the plasma membrane but they do not open

      Best, Thanos
       
      • Informative Informative x 3
    26. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      My take, he's basically repeating what he said in the interview which is: there are two ways you can reduce potassium ion function, either it's gone from the plasma membrane or they are there but closed.

      They have never found a case where they are gone in mice (they tested them with noise injury) from noise and it sounds like don't expect to in people.

      From my reading, certain very specific ototoxins (Ouabain for strial ion channels, Azithromycin for strial +/- brain stem, aminoglycosides for brain stem) can destroy ion channels from the plasma membrane but it doesn't sound like he's encountering that here.

      I think he just wanted to explain the two types and re-iterate he found noise only closes the channels from his studies so far.
       
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    27. Christiaan
      Vegged out

      Christiaan Member Podcast Patron Benefactor

      Location:
      The Hague, the Netherlands
      Tinnitus Since:
      2016
      Cause of Tinnitus:
      Bloody headphones in 2016,worsened in 2020
      Ok. Thanks @FGG! I didn't know ototoxins have a profound effect on that level. I truly hope know one on this forum has damaged ion channels.
       
    28. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I have a very high likelihood of having this problem, unfortunately.
       
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    29. UKBloke

      UKBloke Member Podcast Patron Benefactor

      Tinnitus Since:
      1991
      Cause of Tinnitus:
      Loud Music / family history
      I'm glad you got a reply from him. I didn't. Am still waiting to hear how he and other researchers make the distinction between acute and chronic tinnitus. After reading his articles and hearing him speak I've been left with the impression that his treatment will aim to address acute tinnitus. I hope I'm wrong but would like to hear it from the horse's mouth regardless.
       
      • Good Question Good Question x 1
    30. Christiaan
      Vegged out

      Christiaan Member Podcast Patron Benefactor

      Location:
      The Hague, the Netherlands
      Tinnitus Since:
      2016
      Cause of Tinnitus:
      Bloody headphones in 2016,worsened in 2020
      Have you tried to send him another mail as a reminder? I did the same thing and after a while you get a reply back. I have the idea that he is bombarded with a lot of emails and may overlook some things here and there. Good question btw.
       

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