Frequency Therapeutics — Hearing Loss Regeneration

Discussion in 'Research News' started by RB2014, Dec 8, 2016.

    1. JohnAdams
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      Wth they don't even tell you what the title of the paper is.

      Renewed proliferation in adult mouse cochlea and regeneration of hair cells
       
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    2. FGG

      FGG Member Podcast Patron Benefactor

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      This paper is actually pretty amazing. It seems like this "one two punch" method could regenerate OHCs and IHCs and even some if the supporting structures. I will try to write Dr. Chen this week and ask him more...
       
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    3. FGG

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      Another interesting aspect of this paper is he seems to be using a new model where they grow cochlear cells in a "bony incasing" to mimic in vivo testing. Seems like this could accelerate pre-clinical studies if widely used.
       
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    4. FGG

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      Also looks like Dr. Chen is on the board of something called "Rescue Hearing Inc." Which I can't figure out. Is it a biotech? Private equity investing in biotech? Their website is pop up/virus hell btw. At least on mobile.

      Edit: looks like there is already a thread on this company. Not much since 2017 but with Dr. Chen's results maybe we can expect more soon.

      https://www.tinnitustalk.com/threads/rescue-hearing-inc.22828/
       
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    5. JohnAdams
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      I'm going to see if there are natural substances that can activate these 2 pathways. The targets are MYC and Notch1. Curcumin inhibits Notch1 but other stuff stops it from causing proliferation. Maybe co activating MYC with some other substance is the key.
       
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    6. d'Wooluf

      d'Wooluf Member

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      Awesome. And then you can translate his reply into easy little words for my benefit. :joyful:
       
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    7. FGG

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      If I understand it right, Dr. Chen's approach doesn't inhibit Notch at all but activates it instead simultaneously with another pathway. I will ask for clarification on that in my email, too.
       
    8. JohnAdams
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      Yes, I caught that too. Resveratrol activates Notch.

      "Additionally, resveratrol is a potent activator of the Notch signaling pathway"
      https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210607

      MYC is an oncogene, that is a gene that when activated promotes cancer growth, so... I don't know about this one being an oral route.
       
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    9. FGG

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      Does anyone remember what presentation this is coming from where IHC grow along with OHC for FX-322?
       
    10. mrbrightside614

      mrbrightside614 Member

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    11. FGG

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      I wrote to Jeff Karp trying to get clarification on whether FX-322 regrows inner hair cells or outer and he sent me a form email about ClinicalTrials.gov. Anyone have any idea where and from who can I get this information? I was sure it was the outer hair cells but going through this thread, it sounds like someone thought it was inner.
       
    12. JohnAdams
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      Then get swole and help me research these signalling pathways. I'm the only loser on this website even researching this. It's depressing not having anyone even trying to discuss these things with me, fml.
       
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    13. FGG

      FGG Member Podcast Patron Benefactor

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      I wrote back asking again and he told me to look at their publications page for updates. It was vague but I doubt he could say more since it's a publically traded company.

      I did find this there:

      https://www.cell.com/cell-reports/fulltext/S2211-1247(17)30136-5

      Does this suggest OHCs are more affected to anyone or both? I think I need to re-read it a few times.
       
    14. JohnAdams
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      What? Please rephrase.
       
    15. mrbrightside614

      mrbrightside614 Member

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      Alright but I’m kind of a r*tard because of the tinnitus. Scrambles my brain reading scholarly material—if not my chief concern, then secondary.
       
    16. ChrisBoyMonkey

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      Getting swole will help with ringing?
       
    17. mrbrightside614

      mrbrightside614 Member

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      mTOR is a major pathway by which hypertrophy is achieved. Acute responses to resistance training not only increase androgen receptor activity but stimulate the mTOR pathway, which drives protein synthesis. I don’t know much else about it though, unfortunately. I’ll do some reading now that I’m through the semester, though I don’t know how much help it would be.
       
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    18. FGG

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      Sorry. No idea what that means or what my brain was doing with that sentence. Does it seem like to anyone that OHCs are preferentially generated over IHCs or are both generated?
       
    19. mrbrightside614

      mrbrightside614 Member

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    20. JohnAdams
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      I need to research that. Excellent question.
       
    21. d'Wooluf

      d'Wooluf Member

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      I've never seen anything to suggest that they aren't both generated. For what it's worth. They both have supporting cells.

      From the paper you linked to: "Our differentiation conditions thus generated inner and outer cochlear hair cell types"
       
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    22. FGG

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      It definitely does both but not equally and I was trying to ascertain percentages but my brain can't type a coherent sentence tonight for some reason.
       
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    23. JohnAdams
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      "and there were no significant changes in the numbers of inner hair cells in the treated group"
      upload_2019-12-6_9-38-33.png

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573859/

      Bear in mind this was from the LY411575 drug which I am to understand is not what FX-322 uses. Also, it doesn't look like there was a significant loss of IHCs to begin with.
       
    24. FGG

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      Thanks for finding that.

      Acoustic trauma does not affect IHCs nearly as much (but does some). In fact, the only things that seem to preferentially damage IHC over OHC (that i could find) are Cisplatin and Macrolides (what poisoned me) ototoxicity. Even other antibiotics don't seem to do this. It probably partially explains why my hearing is so messed up and bizarre.

      From this, I suspect this means REGAIN would not work well for those with certain ototoxicity or severe enough threshold changes where IHCs are affected, too. I'm still not sure about FX-322.

      From Dr. Chen's paper, it looks like his method regenerates both. Hopefully will be tested in people soon.

      Edit: forgot to mention, I also emailed Pipeline. Their drug does not affect IHCs at all.
       
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    25. FGG

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      The weird thing is the data for Frequency and IHC vs OHC is in that paper, I just can't decode it. Normally, I don't think I fail quite that bad with research papers but I can't figure it out and my friend who is a PhD in biomedical engineering and a former researcher (for Spina Bifida so unrelated, but still...) couldn't figure it out either.
       
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    26. FGG

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      I had a weird thought... what if Frequency actually helps IHCs more and that's part of why the ones with more severe loss recovered more word scores in phase 1. For most causes, only the severely affected get an appreciable amount of IHC loss.
       
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    27. Reinier
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      But from what I understand, it is the outer hair cells that improve clarity of sound in noisy environments.
       
    28. FGG

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      Source?
       
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    29. grate_biff
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      grate_biff Member Benefactor

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      Thought that was the synapses.
       
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    30. FGG

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      One thing I am sure of is, though, is that most clinical ENTs and Otologists (and Audiologists) are so behind on recent advances in hearing/cochlear physiology that if a bunch of these drugs all came out they won't know what to prescribe to who.
       
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