Prolonging Residual Inhibition with Eglumegad

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

    1. DebInAustralia
      No Mood

      DebInAustralia Member Benefactor Advocate

      Location:
      Geelong, Victoria
      Tinnitus Since:
      30/12/13
      Might be of interest: -

      Read a publication entitled ' 1pAB6 - Long - lasting suppression of spontaneous firing in inferior colliculus neurons: implication to the residual inhibition of tinnitus - A.V. Galayuk'

      Here is the link: -

      http://acoustics.org/1pab6-long-las...residual-inhibition-of-tinnitus-a-v-galazyuk/


      Of significance is the author's comments regarding the research already undertaken on residual inhibition and its ability to help science identify a group of drugs that can alter the suppression response, as well as the 'spontaneous firing of the auditory neurons responsible for tinnitus. These drugs will be further investigated in our future research to develop effective tinnitus treatments.'

      I emailed this researcher.

      This is his response with relation to pharmaceutical developments for tinnitus.

      'The study has just started. We have preliminary results on animals indicating that the drug works to provide tinnitus relief for about two hours. We are planning to test this product on humans, but, even if successful, it will take several years until this drug will be approved by FDA.'

      The name of the drug is 'Eglumegad', which is a group 11 mGluR agonist.
       
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    2. Steinberg

      Steinberg Member

      Location:
      Manchester, UK
      Tinnitus Since:
      April 2016
      Cause of Tinnitus:
      Loud Noise Exposure
      Fascinating...

      Thanks
       
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    3. Frédéric

      Frédéric Member Podcast Patron Benefactor Advocate

      Location:
      Marseille, France
      Tinnitus Since:
      11/19/2012
      Cause of Tinnitus:
      acoustic trauma
      https://www.sciencedirect.com/science/article/pii/S0378595518304635

      Abstract
      Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal “noise” is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.
       
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    4. Clmnt
      Depressed

      Clmnt Member

      Tinnitus Since:
      11/2016
      Cause of Tinnitus:
      Sound Trauma
      Great! Look forward to following their work. For the FDA this is only valid for the United States? If they want to release something in Europe would be faster you think?
       
    5. AUTHOR
      AUTHOR
      DebInAustralia
      No Mood

      DebInAustralia Member Benefactor Advocate

      Location:
      Geelong, Victoria
      Tinnitus Since:
      30/12/13
      Touched base with prof Alex Galazyuk recently.

      He's submitting a grant proposal to the NIH to further his clinical trials.

      Preliminary trials in animals showed relief from tinnitus for two hours using this compound (2016).
       
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    6. Danny B
      Wishful

      Danny B Member

      Tinnitus Since:
      03/2019
      Cause of Tinnitus:
      Ear syringing
      Always love to see a new potential treatment being developed. Even a temporary fix would be lovely, and every bit of research into the tinnitus phenomenon is good news.
       
    7. Thuan

      Thuan Member

      Location:
      California
      Tinnitus Since:
      05/2018
      Cause of Tinnitus:
      Ear infection
      I just read parts of Galazyuk's article. His proposed model of tinnitus certainly makes sense: an increased in spontaneous hyperactivity above a certain threshold is shifted from cochlea to central nervous system; thus we are stuck with tinnitus when the cochlea recovers. This is consistent with studies where the cochlear nerve is severed but tinnitus is not resolved nor improved. It's also consistent where some people with hearing loss do not have tinnitus because that hyperactivity has not shifted to the CNS or the hyperactivity has not reached above a certain threshold.

      I wonder what Dr. Will Sedley's predictive tinnitus model thinks about this.

      So the question is: how likely will healing the cochlea (regenerating damaged hair cells) resolve/improve tinnitus symptoms?
       
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    8. AUTHOR
      AUTHOR
      DebInAustralia
      No Mood

      DebInAustralia Member Benefactor Advocate

      Location:
      Geelong, Victoria
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      Further to this study, when asked about financing, here is the researcher's response:

      Hi Deb,

      We don’t have exact budget yet, but with our rough estimation it will cost about $1,500,000. It will include the drug production and testing of 30-40 people during the trial. This is the phase II clinical trial (the proof of concept). If successful we will need to move to the phase III trial which would require of testing several thousand tinnitus patients. This trial would cost about 150 million dollars. However, if the phase II trial is successful, raising this amount of money would not be so difficult, because all investors would likely to get their money back together with a significant profit.

      Best
       
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    9. WillBeNimble
      Buzzed

      WillBeNimble Member Podcast Patron Benefactor

      Location:
      Ohio
      Tinnitus Since:
      2017
      Cause of Tinnitus:
      Acoustic Damage from earphones
      Wait, they did phase 1 already? Or is this phase 1/2?
       
    10. AUTHOR
      AUTHOR
      DebInAustralia
      No Mood

      DebInAustralia Member Benefactor Advocate

      Location:
      Geelong, Victoria
      Tinnitus Since:
      30/12/13
      I think he's hoping to move to phase 2 because he said earlier that they've already tested its efficacy in animals.
       
    11. WillBeNimble
      Buzzed

      WillBeNimble Member Podcast Patron Benefactor

      Location:
      Ohio
      Tinnitus Since:
      2017
      Cause of Tinnitus:
      Acoustic Damage from earphones
      Phase 1 is safety. Normally, for issues like tinnitus, it becomes a phase 1/2 trial for safety and efficacy. To move to just phase 2 on humans without a safety is unlikely. He probably means phase 1/2.
       

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