Pipeline Therapeutics

Discussion in 'Research News' started by FGG, Nov 14, 2019.

    1. Jurger

      Jurger Member

      Tinnitus Since:
      2004
      Cause of Tinnitus:
      Hearing loss
      We’ll see what it does when they release results in Q1 of 2021. Should be an exciting half year with Frequency, Pipeline and Otonomy releasing important data.
       
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    2. vttbx

      vttbx Member Benefactor

      Tinnitus Since:
      01/2001
      It looks like they have added some locations.

      https://clinicaltrials.gov/ct2/show/NCT04462198
       
      • Informative Informative x 1
    3. asey20
      Curious

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      It's cool how they are not only doing speech in noise and audiometry tests, but also auditory brainstem potential testing. Curious to see what the results will be if successful.
       
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    4. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      So am I. I’m interested in the fact that there are multiple companies currently choosing to treat synapses first. I do think that this is a bit different with the treatment of outer hair cells too.

      The interesting thing is whether the outer hair cells are unique to PIPE-505 or whether the competing similar treatments such as the Hough treatment are able to treat these as well.
       
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    5. AUTHOR
      AUTHOR
      FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I see that it's a phase 1/2a as well so it's possible they may add even more locations (vs. phase 1 which is usually just a couple).
       
    6. asey20
      Curious

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      I recently read an article where tinnitus was induced into rats and they noticed that the IHC and OHC were largely intact, but the cochlear synapse ribbons were affected. This means that it's potentially more important to repair the synapses then regrow the hair cells.

      This kinda makes me lose hope for FX-322. On the contrary, FX-322 got excellent speech-in-noise test results, which is usually an indicator or synaptopathy. All this leaves me very confused.

      The good news is that both frequency therapeutics and pipeline therapeutics have similar pipeline models. Both are working on drugs for hearing loss, albeit different approaches, and both have upcoming MS trial drugs. I guess this is reassuring because it's a different approach than what Auris Medical was doing in the past.
      The Hough pill doesn't inspire confidence for me. It would be nice but just doesn't seem like it will work.
       
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    7. AUTHOR
      AUTHOR
      FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Tinnitus is "phantom cochlea" in the brain.

      The signal is reduced or cut off somewhere. In some people with cochlear causes (e.g. not middle ear, TMJ, etc), tinnitus is caused by damaged synapses, in others, it's hair cells and still others it's both.

      Frequency has good anecdotes but obviously, their trial candidates had at least some hair cell component.

      Some people will do better with synaptopathy drugs for sure.
       
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    8. asey20
      Curious

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      Wondering how they will be able to determine if it is synaptopathy or hair cell issues. Maybe eventually both drugs will be used in conjunction to get best results.
       
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    9. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      I think that there will be a huge likelihood that treatment will be required for both but there will also be an overlap between the two treatments.
       
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    10. AUTHOR
      AUTHOR
      FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Diagnostics will have to catch up to treatments at some point. It's likely a lot of people will trial treat to see what helps.
       
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    11. AnxiouslyWaiting
      No Mood

      AnxiouslyWaiting Member

      Tinnitus Since:
      03/2020
      Cause of Tinnitus:
      Anxiety maybe?
      I feel that’s a huge part of the problem with trying to fix tinnitus. It’s so hard to diagnose what’s causing it for different people.
       
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    12. Bartoli

      Bartoli Member

      Tinnitus Since:
      2009,worsened 2019
      Cause of Tinnitus:
      Noise
      Is there even a situation conceivable where one would have solely one or the other?
       
    13. Bartoli

      Bartoli Member

      Tinnitus Since:
      2009,worsened 2019
      Cause of Tinnitus:
      Noise
      Stupid question maybe, but am I right that the synapses connect IHCs to OHCs? In that case, would tinnitus lessen when these hair cells die off? Could that be the case when people report a lessening or fading of symptoms?
       
      • Good Question Good Question x 1
    14. AUTHOR
      AUTHOR
      FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      The synapses connect the IHCs to the Spiral Ganglion nerves.
       
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    15. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Unknown, although an eligibility criteria for OTO-413 clinical trial is that you have normal hearing and/or mild hearing loss.

      Thus it seems Otonomy thinks that a person can have normal hearing according to an audiogram but also have trouble with speech in noise.

      https://clinicaltrials.gov/ct2/show/NCT04129775
       
    16. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Savvy specialists will take records of what treatment(s) worked with what patients, based off their condition(s).

      This way they will at least have some idea on what they could prescribe by matching data from past failures or successes with similar patients and working out what might be appropriate.
       
    17. Bartoli

      Bartoli Member

      Tinnitus Since:
      2009,worsened 2019
      Cause of Tinnitus:
      Noise
      According to you, would IHC/OHC death result in the lessening of tinnitus/distortion/speech in noise problems? How is the synapse theory compatible with tinnitus coming from the brain?

      I'm just mentioning tinnitus as it sometimes comes up, I am aware the the
      drug is for synaptopathy, which may also cause tinnitus according to some, and not according to others.
      I think the problem will not be data collection after treatment, but proper assessment upon start of the treatment. If we lack the diagnostic tools to categorize patients, what will they do with the collected data?

      It'll simply tell them *some* people improved on speech in noise.
       
    18. Jurger

      Jurger Member

      Tinnitus Since:
      2004
      Cause of Tinnitus:
      Hearing loss
      Better treatment capabilities will likely raise the demand for better diagnostics. Right now, being able to tell what kind of damage your cochlea has via imaging technology, doesn’t make a difference for the kind of treatment you get, since there are no treatments for inner ear issues (prednisone and other off-label treatments aside).
       
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    19. AUTHOR
      AUTHOR
      FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      This is how I understand it.

      Tinnitus is the response of the brain to decreased auditory input (or input that is interfered with in some way) at some point (It varies from individual to individual. It is "phantom limb" of the auditory system.

      Death of cochlear structures doesn't result in an improvement, just like you wouldn't treat phantom limb with more amputation.

      I think the reason tinnitus improves for many is either they have a treatable or fluctuating underlying cause or co-factor (e.g. eustachian tube, TMJ, treated Meniere's, etc) or in cases of permanent damage you have something like this:

      X + Y + Z = tinnitus, where X is structural damage, Y is neuro-inflammation, and Z is intrinsic factors like receptors (it might actually look like X + XY + XZ or X + XY + Y + YZ + Z etc in some cases because these things can be interrelated more closely for some conditions than others but just for simplicity's sake, let's say X + Y + Z).

      Anyway, the reason tinnitus improves for most people is the "Y" often gets better in the first few weeks, months. Inflammation isn't self sustaining unless you have a continued stimulus or auto-immunity. For these people, the structural damage, X, was not eclipsing Y and Z values.
       
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    20. paul mclean

      paul mclean Member

      Tinnitus Since:
      2018
      Cause of Tinnitus:
      falling asleep with headphones in on loud
      Found this on one of Pipeline Therapeutics patents.

      Direct quote from the patent - "Treatment with oral NGP-555 significantly increased the number of synapses on inner hair cells (FIG. 5), demonstrating the efficacy of GSMs for the treatment of synaptopathy."

      NGP-555 is a small-molecule modulator of γ-secretase and has been successful in achieving good oral absorption, brain penetration, CNS activity, and specificity for a lipid-based membrane target preclinically.

      Seriously considering giving this a go.

      https://www.freepatentsonline.com/y2019/0307746.html
       
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    21. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      Incredibly I think this stuff is coming together. Great post.
       
      • Agree Agree x 1
    22. weab00

      weab00 Member Benefactor

      Tinnitus Since:
      04/2019
      Cause of Tinnitus:
      Headphone use/concerts, neck whiplash
      I’ve only been loosely following the thread, but when can we expect for this thing to hit the market? Under 5 years? 3? The waiting is so torturous.
       
    23. paul mclean

      paul mclean Member

      Tinnitus Since:
      2018
      Cause of Tinnitus:
      falling asleep with headphones in on loud
      @tommyd87

      I am going to try it in the next month or so. Will let you know how it goes.
       
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    24. tommyd87

      tommyd87 Member

      Tinnitus Since:
      1999
      Cause of Tinnitus:
      tmj music
      It is in the middle of its phase 1/2 trial. The thing is I don’t know whether it is being fast tracked and also approved for expanded access. If the phase 1/2 trial is somewhat successful and expanded access is granted then I could see this getting released potentially in early 2022. This is because it will probably take at least six months for the phase 2 trial, then a few months for the results to be submitted and also for FDA approval to be granted.
      How are you doing that out of interest?
       
      • Agree Agree x 1
    25. PauloZ
      Alienated

      PauloZ Member Benefactor

      Location:
      Netherlands
      Tinnitus Since:
      06/2015, got much worse in 09/2019
      Cause of Tinnitus:
      Loud noise exposure, both times.
      You are going to try it? Do you mean you have access to this NGP-555?
       
    26. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Is it available?
       
    27. asey20
      Curious

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
    28. paul mclean

      paul mclean Member

      Tinnitus Since:
      2018
      Cause of Tinnitus:
      falling asleep with headphones in on loud
      @asey20

      Read Pipeline Therapeutics' patent. It is mentioned a couple times along with other orally active Gamma-secretase inhibitors/modulators.

      RO4929097 and BMS-708163 were also mentioned.

      Here's a quote from the patent:
      I have also read the Alzheimer's studies, it is well tolerated in humans. At this point I'm willing to try anything, except what that John guy did and go to South Korea haha.

      https://www.freepatentsonline.com/y2019/0307746.html
       
    29. asey20
      Curious

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      How are you able to get this drug though?
       
    30. paul mclean

      paul mclean Member

      Tinnitus Since:
      2018
      Cause of Tinnitus:
      falling asleep with headphones in on loud

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