Update on AM-101 (aka Keyzilen)

Discussion in 'Research News' started by Aaron123, Jun 15, 2016.

    1. Mic
      Buzzed

      Mic Member

      Tinnitus Since:
      -
      Well... in the 'dark scientific age' we live in, pre-clinical trails on animals who can't tell us if they have tinnitus, nor if any intervention is effective in supressing it, are considered common practice in drug discovery. Take in account that a substantial part of medicines now in use are discovered by sheer luck... hell we even don't now exactly why a common painkiller like paracetamol acts on the biology of humans... we learn by trail and error... not by reasoning and developing drugs with science based methods...

      This is, from my point of view, the core reason why Auris failed, and many others will fail in the future, till some pharma company wins the lottery by pure luck.

      Public health related matters should be considered common goods. Approaching drug discovery with capitalistic ideas leads to corruption of goals. Scientist won't work for proving the efficacy of new drug but to save the earnings of shareholders. This is why so many ineffective garbage (like many anti-depressants) or dangerous drugs (like our beloved Retigabine) is still pushed to the market.

      No, they would first of all protect their 'discovery' by patents and stop others from using their data to further improve efficacy. Second they would build upon minor improvements on the same half proven mechanism of action to extend patents and generate more revenue. It's like cars. The past 100 years every car manufacturer played for safe by improving little and shoving up the same in a new package again and again...till...

      Musk... we need many more Musks... visionairs who aren't afraid of taking risks and are considering money as an instrument... not the goal of our existence...
       
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    2. Pleasure_Paulie

      Pleasure_Paulie Member

      Location:
      Australia
      Tinnitus Since:
      06/2016
      Cause of Tinnitus:
      Noise or maybe... unicorns!
      Well coming from somebody who works in pharmaceuticals, this is simply not the case for majority of medications, while it may be true for Panadol. They start with a firm scientific hypothesis as I suspect Auris medications did. There is a lot of smart people working very very hard on drug development. Yes, some drugs do yield benefits to other conditions in phase 3 which later often becomes its primary use but it’s extreme to say most drugs were discovered this way. In fact some of the new developments in drug discovery using machine learning is going changing a lot moving forward.

      That is idealistic. We would not have half our medications if it wasn’t for big Pharma and when we have treatment for tinnitus it will probably be by big Pharma due to the gap in the market currently and profit potential. People hate on big Pharma, that is until one of the drugs saves a loved one or helps you personally. Yes, some of their behaviour is unethical; I’m looking at you Valent pharmaceuticals!

      Tobalt was innovative and revolutionary and helped many people with Epilepsy that did not respond to other meds. I’m confused, you’re angry at GSK for getting this to market, yet it’s one of the few drugs that helped tinnitus sufferers? Yes it’s safety profile was poor, so GSK did the correct thing and removed it from shelves. Plus this design has prompted other companies to build upon this innovation.

      And they have a right to protect their patient. If you spent 10+ years and billions in r&d would you not protect this? Pharmaceuticals is not at all like cars, changing and finding new compounds and clinical testing is very diffident from changing the design or engine of a car. And the cost is not be comparable at all.

      You’ve been had. Musk is a marketing genius and everything he does is about building the brand equity of his companies and his own name through brilliantly orchestrated stunts. His companies must run at a profit just like others to exist. He does not run charieties.
       
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    3. Contrast

      Contrast Member Benefactor Hall of Fame

      Location:
      Retrovile
      Tinnitus Since:
      late 2017
      Cause of Tinnitus:
      injury from noxious noise
      I think Auris Medical has an problematic model of tinnitus, it is probably not generated within the auditory nerve.
      NMDA blockage prevents more hair cell death from occurring, that explains why it helps tinnitus and excelled to Stage 3 trials

      Therefore AM-101 could actually be acute hearing loss treatment based blocking NDMA to save hair cells from additional damage in cases where NMDA receptors add insult to injury after acoustic trauma

      upload_2018-7-13_15-45-53-png.png
      I agree with everything about the part stating "aberrant excitation of the audiotory nerve that is perceived as tinnitus" The auditory nerve itself is not generating the tinnitus signal, it's in the brain even in acute phases. If I understand correctly it is the Dorsal Cochlear Nucleus.


      The central gain model is here I posted it a many times
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208401/
      In a nutshell hearing loss causes less input from the audiotory nerve (not more) + higher brain functions compensating is the cause of tinnitus.

      This explains why all forms of hearing loss from SNHL, middle ear surgery to ear plugs and ear wax have potential to lead to tinnitus. Anything that deprives the auditory nerve or even parts of the audiotory brain can cause tinnitus if one subscribes to central gain model. I don't think that is the case for the NMDA model of tinnitus

      It's a shame there trial failed though, it would have helped acute sufferers

      Unless they have a way to explain how ear plug experiments and ear wax can give healthy hearing people tinnitus the NMDA model of tinnitus is missing something and central gain model adds up a lot more. Then again I am just a mentally ill person on a tinnitus forum and not a researcher.

      I am just confused why there are two models of tinnitus that contradict each other and only one holding up.

      If there is something I am missing can someone please help me. I actually care about being less wrong
       
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    4. Greg Sacramento

      Greg Sacramento Member Benefactor Hall of Fame

      Tinnitus Since:
      April 2011
      Cause of Tinnitus:
      syringing and now somatic T dental work
      The cell is responsible for signaling is a neuron. Presynaptic neurons transmit signals, whereas postsynaptic neurons react to signals. Neurotransmitters are released by a presynaptic neuron over the synaptic space and bind to and interact with receptors on a postsynaptic neuron. Focus on extrasynaptic receptors that respond to neurotransmitters has been discovered showing that the most important receptors are GABAa and NMDA.

      A therapy drug company with a partner have been given the FDA green light for final stage treatment trials that are now ongoing for neuro conditions. A separate trial just for tinnitus has been expressed to follow, but the current developed drugs should be available soon as Wall Street thinks so. An interview with CNBC took place last week. Money talks and often shows greed reality over actual suffering.

      I don't understood the science above to any extent, but I wish the name Tinnitus was changed to Hearing Disorder.
       
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    5. xCyborg
      Frustrated

      xCyborg Member

      Tinnitus Since:
      02/2018
      Cause of Tinnitus:
      Headphones/Noise? Prolonged Stress/D? TMJ/Neck/Head?
      What drug company is that?
       
    6. Greg Sacramento

      Greg Sacramento Member Benefactor Hall of Fame

      Tinnitus Since:
      April 2011
      Cause of Tinnitus:
      syringing and now somatic T dental work
    7. xCyborg
      Frustrated

      xCyborg Member

      Tinnitus Since:
      02/2018
      Cause of Tinnitus:
      Headphones/Noise? Prolonged Stress/D? TMJ/Neck/Head?
    8. Greg Sacramento

      Greg Sacramento Member Benefactor Hall of Fame

      Tinnitus Since:
      April 2011
      Cause of Tinnitus:
      syringing and now somatic T dental work
      @xCyborg Hi: As briefly mentioned above - they hope to enter the tinnitus space. Place SAGE into search above on this page and read the postings and links. Research of compounds and pathway of neuro involvement is discussed. It may be that their depression drug which should have final results towards the end of this year will help with tinnitus perception. The depression drug is not a benzo and has been proven safe in other trials. The ween off period is 4-5 days.
       
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    9. Jiri
      No Mood

      Jiri Member Benefactor

      Tinnitus Since:
      11/2017
      Cause of Tinnitus:
      noise + injury
      Sorry, I am not sure I understand. Ear plugs can give people tinnitus? Do you mean the occlusion effect or smth else?
       
    10. GregCA
      Jaded

      GregCA Member Benefactor Hall of Fame

      Tinnitus Since:
      03/2016
      Cause of Tinnitus:
      Otosclerosis
      Something else:

      Heller and Bergman (1953) conducted a study of 80 tinnitus-free university students placed in an anechoic (soundproof) chamber and found that 93% reported hearing a buzzing, pulsing or whistling sound.
      Depriving the ear of sensory input (which is what ear plugs do) can induce T.
       
      Last edited by a moderator: Dec 3, 2018
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    11. Jiri
      No Mood

      Jiri Member Benefactor

      Tinnitus Since:
      11/2017
      Cause of Tinnitus:
      noise + injury
      True. I have heard of that study. Our brains don't like silence. It just came across to me from Jon's post that wearing ear plugs (as to protect ourselves from noise when outside) can literally give us tinnitus.

      I certainly hear my tinnitus louder when wearing hearing protectors.
       
    12. RingerBell

      RingerBell Member Benefactor

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      Noise
      This just makes me wonder, because if one doesn't stay still, like sleep, with plugs, there's still some thudding and rumbling going on even in silent environments.
       
      Last edited by a moderator: Dec 3, 2018
    13. Jiri
      No Mood

      Jiri Member Benefactor

      Tinnitus Since:
      11/2017
      Cause of Tinnitus:
      noise + injury
      Like pulsatile tinnitus? Otherwise, yeah. Even when my healthy, tinnitus-free friends, plug their ears they still can hear some mild whooshing sound somewhere in the background. May be it's an age related thing too.
       
    14. RingerBell

      RingerBell Member Benefactor

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      Noise
      Yes, heartbeats, sound of foot hitting the ground,sound of muscle contractions, sound of breathing, etc...
       
      Last edited by a moderator: Dec 3, 2018
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    15. GregCA
      Jaded

      GregCA Member Benefactor Hall of Fame

      Tinnitus Since:
      03/2016
      Cause of Tinnitus:
      Otosclerosis
      If I recall well, in the studies, the tinnitus induced was only temporary. I imagine that the longevity of T is correlated with the length of sensory deprivation, but I don't have any data to back this up.
       
      Last edited by a moderator: Dec 3, 2018
    16. Jiri
      No Mood

      Jiri Member Benefactor

      Tinnitus Since:
      11/2017
      Cause of Tinnitus:
      noise + injury
      I don't want to hijack this thread but yes, those were healthy individuals. Their tinnitus was temporary. The point you made is quite interesting.
       
    17. Laurie1961
      No Mood

      Laurie1961 Member

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      dental work
      This has nothing to do with sensory deprivation. In fact quite the opposite. Temporary tinnitus may be related to the same cause as long-lived tinnitus. I've had tinnitus for over ten years and I am telling you with relief comes a few other sentiments. One is that others need to be helped. The second is that anyone pulling anymore quackery needs to be called out.

      For instance, it is well known that one can cancel a frequency with an identical frequency so any frequency fix for T is likely going to be a temporary fix. The same for hyperbolic pressure chamber, if it works at all is because it changing air pressure. Did you know that gold-miners who had tinnitus in the 19th century were reported to have noticed that relief of tinnitus was found, by going back down into the mines?

      We who have tinnitus have something in common with the gold miner. High levels of mercury and another critical chemical that is released internally from a fungus or gram negative bacteria overgrowth: cyanide. The miners used both mercury and cyanide to melt metals. We got chemicals from medical treatments, food, food additives (xanthan gum thickener) --all things approved by the FDA and USDA.

      Once you are on the right track self-help is not far off. First step is to take vitamin B12, to counter the cyanide overload.
       
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    18. Flamingo1

      Flamingo1 Member Benefactor

      Location:
      Orlando, FL
      Tinnitus Since:
      4-15-2017
      Cause of Tinnitus:
      Acoustic trauma
      What does cyanide have to do with tinnitus?!
       
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    19. CricketEars

      CricketEars Member Benefactor

      Tinnitus Since:
      10/2003
      Maybe some people with tinnitus take it to help them sleep? :woot:
       
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    20. Silvio Sabo
      Pooptoast

      Silvio Sabo Member Benefactor

      Location:
      Gothenburg, Sweden
      Tinnitus Since:
      05/2006
      Cause of Tinnitus:
      Noise - I think
      Yes, you get the longest sleep from cyanide.. :p
       
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    21. Laurie1961
      No Mood

      Laurie1961 Member

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      dental work
      Heavy metal causes ringing in the ears especially if it is "kicked" back up into circulation. Cyanogenic bacteria dissolve metal in the body. "Vitamin" B12 is really just an anti-cyanogenic, needed when there is not enough good bacteria in the body to counter to counter the bad cyanogenic bacteria.

      As far as the shower question, tinnitus gets worse, another reason could be lithium in the water supply or a compilation of that and the above. I don't know if it happened or not but there was talk of putting lithium in public water and bottled water.
       
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    22. threefirefour
      Rebellious

      threefirefour Member Benefactor Hall of Fame

      Location:
      California
      Tinnitus Since:
      5/15/16
      Cause of Tinnitus:
      140dB B R U H moment
      Isn't that the truth?

      superthumb.jpg
       
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    23. Paulmanlike

      Paulmanlike Member Hall of Fame

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      Noise
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    24. Contrast

      Contrast Member Benefactor Hall of Fame

      Location:
      Retrovile
      Tinnitus Since:
      late 2017
      Cause of Tinnitus:
      injury from noxious noise
      acute peripheral tinnitus doesn't exist, tinnitus is always neuro, never peripheral
       
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    25. Paulmanlike

      Paulmanlike Member Hall of Fame

      Tinnitus Since:
      2008
      Cause of Tinnitus:
      Noise
      The share price jumped up 60% today
       
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    26. sky_high

      sky_high Member Benefactor

      Location:
      Berlin / Bucharest
      Tinnitus Since:
      08/2018
      Cause of Tinnitus:
      lexapro / stress / unknown
      I have just found that paper. I'll leave here a link to it in case someone is interested. It's a good read.

      http://www.atlantatinnitus.com/downloads/HellerBergman.pdf

      "A sound-proof chamber was used. The ambient noise level was probably between 15 dB and 18 dB"

      Nowadays there are anechoic chambers that register negative decibels (-10 dB) and the effect is even more dramatic.

      http://blog.shure.com/an-inside-look-at-an-anechoic-chamber/

      "The quieter the room, the more things you hear. You’ll hear your heart beating; sometimes you can hear your lungs, or hear your stomach gurgling loudly. In the anechoic chamber, you become the sound.” Some visitors find the anechoic chamber experience so disquieting that there have been reports of nausea, dizziness, panic attacks and even aural hallucinations."
       

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