Hough Ear Institute's Hair Cell Regeneration Project

Discussion in 'Research News' started by all to gain, Oct 2, 2019.

    1. HootOwl

      HootOwl Member Podcast Patron Benefactor Advocate

      Location:
      California
      Tinnitus Since:
      2009
      Cause of Tinnitus:
      Explanation in About You
      As far as I’m aware, no. But I’m curious why you think you have damage to the SGNs or auditory nerve. Even profoundly deaf individuals have been found to have nearly the same number of SGNs as hearing individuals at death. The likelihood that you will need Rinri is very small imo.

      FX-322 isn’t regrowing nerve fibers directly. By causing a new IHC to form the SGNs that you have recognize this and send out nerve fibers to attach to the newly regenerated inner hair cell. In this way we see it as a “pseudo-synaptopathy drug” for those with IHC loss.

      This is in contrast to Hough and Pipeline who need your IHC to be intact to begin with. Their drugs stimulate growth of the nerve fibers directly.

      But if your IHC are intact the nerve fibers will not be stimulated to regrow and attach. I think the confusion comes from people not really being familiar with the SGNs. These are cell bodies that form a bulb at the end of the auditory nerve and are responsible for generating the afferent nerve fibers you see attaching to the IHC s and OHCs. In cases of synaptopathy the drugs we currently see address only these A1 fibers - not the cell bodies themselves.
       
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    2. Ben S
      Curious

      Ben S Member

      Location:
      Connecticut
      Tinnitus Since:
      11/2015
      I believe I have this kind of damage because my ears hurt without being triggered by sound, and I have pain radiating around the jaw area too. I feel like this is a kind of nerve damage.
       
    3. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Ear pain is not from auditory nerve damage, neither is jaw pain. Do you have TMJ?
       
    4. HootOwl

      HootOwl Member Podcast Patron Benefactor Advocate

      Location:
      California
      Tinnitus Since:
      2009
      Cause of Tinnitus:
      Explanation in About You
      And you’ve ruled out any form of TMJ? I used to get pretty bad ear and jaw pain like what you’re describing from even the most mild of clenching - the kind that was imperceivable to me. I don’t think that kind of pain automatically means there is direct damage to your auditory nerve. Have you tried a mouth guard at night?
       
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    5. Ben S
      Curious

      Ben S Member

      Location:
      Connecticut
      Tinnitus Since:
      11/2015
      Yes, I have been told by dentists predating any of this hearing stuff that I have mild TMJ. I still get clicks and cracks from it, but I remember hearing that ear issues can cause some TMJ like problems such as jaw pain since all the nerves are so close together. Also when it's cold enough out, I get INTENSE inner ear pain... like near excruciating. Idk if that's connected to any of this though.
       
    6. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Cold weather increases joint pain, including TMJ pain.
       
    7. Ben S
      Curious

      Ben S Member

      Location:
      Connecticut
      Tinnitus Since:
      11/2015
      That's comforting to hear, because wow does it hurt. That has been an issue that I've had for my entire life. Perhaps my TMJ issues made me more susceptible to getting this tinnitus and hearing loss from noise...interesting. Also @HootOwl, I have never tried a mouth guard, but I might look into it.
       
    8. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      TMJ directly can cause tinnitus and sometimes hearing distortions as well. It's at least something you can look into now. You don't have to wait for drugs in trial and, who knows, it may be most of your problem.
       
    9. HootOwl

      HootOwl Member Podcast Patron Benefactor Advocate

      Location:
      California
      Tinnitus Since:
      2009
      Cause of Tinnitus:
      Explanation in About You
      Happens to me too but not quite to that level. FGG is right, this doesn’t really involve the auditory nerve or SGNs. These treatments should help you.
       
    10. d'Wooluf

      d'Wooluf Member

      Tinnitus Since:
      2010
      Cause of Tinnitus:
      unknown
      I agree. I was trying to encapsulate a view held by a significant number of people on this forum.
       
    11. Tweedleman

      Tweedleman Member Benefactor

      Tinnitus Since:
      2001
      Cause of Tinnitus:
      Unknown/Noise
      @FGG @HootOwl
      Are there other symptoms of synaptopothy other than speech in noise?

      Ever since my trauma I've noticed a reduced ability to hear speech, especially my own voice, in big open areas like the warehouse I work in. If there's no walls/acoustics for the sound to bounce off of it's like my voice falls flat on the floor and is low/muddy. It seems my ears both have difficulty hearing around obstacles now, too. I could barely make out what someone was saying to me standing on the other side of a scissor-lift for example. I also struggle to understand if someone speaks without facing me. It's as if each ear only picks up sound clearly that is coming in within a narrow range of the ear. Before, my ears both seemed to be able to hear in a 360degree manner around my head. Now it feels like my head itself is an obstacle and each ear hears less from the opposite side. If I cone my ears forward I can hear my own voice more succinctly or "together."

      Just wondering what structure in my ear is malfunctioning. My audiogram up to 8kHz is normal with slight loss. OHC, IHC, stereocilia, or synaptic loss?
       
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    12. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I don't think anyone knows the answer to this, yet. To complicate this, I personally believe that IHC loss or synapse loss can both produce "synaptopathy" symptoms because you are still losing the IHC synapses if the hair is gone, too.

      There is no reliable test that I know of, not even using symptoms. The best you can say is that certain things (e.g. noise) are more likely to effect synapses first but even that is not a guarantee i don't think.

      It's too bad we can't get Kopke on this thread to ask him stuff like this but as I understand he's super busy (in fact, I will have to look for a new Otologist because apparently he is retiring from clinical practice to focus on research and development at Hough).

      I do believe as regenerative medicine becomes a reality, though, we will have a better idea of what structural damage produces what symptoms.
       
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    13. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      Frequency Therapeutics has privately licensed FX-322 to Astellas Pharmaceuticals, a massive company that I’m thankful bought into FX-322. But this isn’t the case for SO many valuable studies and treatments for tinnitus. Hough Ear Institute is a non-profit and faced a huge challenge in taking on investors before entering phase 2, and thankfully they’ve secured that in Oblato. But this is why capitalism is toothless in many instances. Major players like Astellas determine winners and losers, when there should be better central oversight as to what is valuable in advancing the understanding of disabling conditions’ pathologies. Their funding is not a product of the government finding value in them; it’s a product of private financial gain. Morally this makes a big difference, but I don’t even care to make that argument because I just want every efficacious therapy to be seen through to the bitter end, regardless of how it’s financed. Right now the system is paying off in the instances of Hough Ear Institute and Frequency Therapeutics, but what if Thanos can’t get an investor for RL-81? The obstacle that the non-profit Hough Ear Institute once faced is a premium example of why this is a problem. Breakthrough therapies are dependent on the capital of wealthy investors to justify their merit. The DoD only paid ONE firm out of 74 applicants a $1.9 million contract, which IMO is disrespectful considering their annual payouts to tinnitus disability. It’s just nothing compared to what it takes to get a drug through FDA-regulated clinical trials. It’s ridiculous. Genius developments should not be at the mercy of wealthy investors.

      What can the American Tinnitus Association do? They can platform the Hough Pill and crowdfund the additional $435k to take it through tinnitus trials. But they refuse and hide behind a facade of “a successful track record with seed grants” matador-esque cookie-cutter responses.
      Political complacency = DoD’s infinitesimal investment in curative treatments compared to their payouts. The ATA being a do-nothing organization that shares no meaningful dialogue with us. The entire capitalist mentality of “winner (discoverer/investor) take-all.” Socialize medicine, fund research 20x over and cut the military budget already.

      When dealing with veterans associations, you have to climb the “chain of command.” It’s not like the president of the main organizations like the DAV, VA, VFW, Wounded Warrior and American Legion have an open-door policy and readily available email addresses to contact them. It requires a lot of planning and waiting and hoping, which is what I’m currently doing with the Tinnitus Talk staff. It’s a pretty maddening process and nothing is cut-and-dry.

      How to fix it? Make major organizations like every one I’ve mentioned way more transparent so they can receive input and build better relationships with those of whom they aim to benefit.
      I highly disagree. It’s most commonly a symptom of hearing loss. Treating that in the currently available ranges has historically rendered consistent results.
      You don’t have damage at the SGN, even the profoundly deaf mostly don’t. You’d need Hough pill, PIPE-505 or OTO-413 to regenerate the auditory nerve, though FX-322’s restores HC’s do forge new synaptic connections, or otherwise they’d just be vestigial components.
      Me2dude.
       
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    14. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Frequency recently tweeted an article suggesting that, most of the time, clinical stage biotechs do not have any difficulty getting the funding they need and that the NIH should fund more general "basic science" instead because these are the blueprints research needs to build on before the future profit becomes obvious. It was an interesting take.

      If the ATA actually does fund seed grants, that might be a net good to have seed money launching research at the very early stages, too

      It is super frustrating that Hough has to raise funds for their pill but because they are a non-profit, but they might be the exception and not the norm. They might not have the same kind of relationship with biotech investment funds, etc.

      All you would need is one wealthy donor with tinnitus to fund the half a million, though, perhaps something like the Gates Foundation or an individual philanthropist who has tinnitus who isn't aware of this drug might help. I wonder if a musicians' organization even would be interested in knowing about the pill.

      I so totally agree with you on organizational transparency, though.
       
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    15. ThomasRobert

      ThomasRobert Member

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      David Rockefeller had 3.3 Billions... you can see him not bothered wearing his hearing device :(

      David Rockefeller Dead at 101 -Breaking News...
       

      Attached Files:

    16. Rb86

      Rb86 Member

      Tinnitus Since:
      5/31/19
      Cause of Tinnitus:
      Noise
      That's a bit of a reach. Yes, a common correlation of tinnitus sufferers is hearing loss. But that's not the rule. Stress, TMJ and ototoxicity are causes as well. Not to mention you can have hearing loss and no tinnitus. Therefore nothing is mutually exclusive.

      "Treating hearing loss in the current available ranges has historically rendered consistent results". Currently available meaning hearing aids and results meaning it doesn't work? What are you getting your info from?
       
    17. MrCrybaby

      MrCrybaby Member Benefactor

      Tinnitus Since:
      2014, 10/2019
      Cause of Tinnitus:
      School Band, Acoustic Trauma
      Facial pain radiating from the ear is a standard hyperacusis symptom. The hyperactivity of the middle ear muscles (the clicking and popping and fullness TTTS type stuff) aggravates the nerves that signal these muscles.

      Read more here if you’d like: https://hyperacusisfocus.org/research/symptoms/

      Avoid coming up with your own theories for your symptoms. I spent a month worrying that I broke my ossicles, I actually had major fluid build up. Good research keeps you sane!
       
    18. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      I’d just like to see one compelling study that declared funding through the ATA so that a “track record with success” could be substantiated for a condition that has not been cured and consistently displays various mechanisms by which it may act that have not been appropriately followed up on.

      Example: Intratympanic Dexamethasone in the Treatment of Acute SSNHL and tinnitus.

      -Hold a conference for PCP’s and GP’s to raise awareness about referring patients with these complaints to trial centers and stress the need for immediacy (<1 month since onset)

      -Conduct extended pure-tone audiometry and speech-in-noise tests at baseline

      -Record time of patient registration relative to onset

      -Deliver the drug on whatever dosing schedule appears most prudent

      -Have patient follow-up testing at 1-month, 3-months, 6-months and 12-months post-administration

      The fact that there is very little useful scholarly data for the only available preventive intervention for chronic tinnitus is unacceptable. This would be my first move as ATA president. Then you can start looking into comparison vs. placebo (or just cross-examine no-treatment tinnitus progression research), comparison vs. oral prednisone/adjunct therapy, neural imaging, lidocaine MOA’s, sleep architecture & effect of REM, etc.

      If we had appropriate distribution of grants, companies like Otonomy might not have to waste their time messing with gacyclidine and ChrisBoyMonkey would be better off. I’m not saying OTO-313 will flop, or that dexamethsone treatment is tried-and-true, but that’s why you FUND the hell out of it for appropriate scientific understanding. It’s cheap as hell, and it makes no sense as to why it’s not the first thing on PCP’s and ENT’s lips when a patient presents with SSNHL.
       
    19. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      Several members of this board in addition to the patients of Dr. Kopke respond well when tinnitus tones are in the ranges hearing aids address. The figures Kopke produced/estimated are in this thread, probably only a page or 2 back.
       
    20. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Oh if that's what the ATA does with funding, that's pretty useless. At least groups like the Hearing Health Foundation fund valuable new research. So is the ATA the Susan Komen of tinnitus?

      I would argue that the problems with OTO-313 have nothing at all to do with funding, though. My guess is they don't yet know what subtypes and what time frames the drug will help. Maybe basic science around subtyping would have helped with that which was kind of the point of the link Frequency posted. Otonomy had enough money to spend on pre-clinical work and IND enabling studies. They also had results of AM-101, so I am really not thinking funding was the problem in that case.
       
    21. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      That is the exact analogy that comes into my head when comparing them to a known quantity. Susan G. Komen may be a private non-profit and not centrally funded though, I’m not sure.

      This is why people hate bureaucracy—it’s bloated and operates behind smoke and mirrors when they should be BY the people FOR the people, since our taxes pay for their existence.

      I was just demonstrating HOW EASY it would be when you have a name-brand organization that holds an annual conference with presumably high participation of practitioners. It would be incredibly easy to disseminate information about trials and compliance would be high because people obviously want to take whatever they can, as soon as they can to silence the banshee that’s developed in their ears. I have never seen a study I’ve liked declare funding by the ATA, and you have to declare it if it was through grant funding.
       
    22. ajc

      ajc Member

      Tinnitus Since:
      11/2002; spike 2009; worse 2017-18
      Cause of Tinnitus:
      Loud music - noise damage
    23. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      He gave them a shoutout for his first grant. It wasn’t the $2m grant, that was supplied by the DoD. I’m sure the first grant was for far less (speculation), and would like to mention that $2 million really isn’t all that much money. It certainly won’t bring a drug through trials, as we’ve seen here.
       
    24. lymebite
      Vegged out

      lymebite Member Podcast Patron Benefactor

      Location:
      United States
      Tinnitus Since:
      2013
      Cause of Tinnitus:
      Unknown
      Everyone should keep in mind that the ATA is a relatively small organization that struggles to raise money. In the most recent year they have provided financial results (their fiscal year ending June 30, 2017), they raised a grand total of $827,727.

      Of this amount raised, only $130,258 went to grants. Better than nothing I suppose, but a drop in the bucket. $2 million is not much, and $130,258 is a whole lot less. :(

      The full tax return with this information and more is available on the ATA website.

      Link to all ATA financial reports:

      https://www.ata.org/about-us/annual-reports

      Direct link to the most recent tax return for their fiscal year ending June 30, 2017:

      https://www.ata.org/sites/default/files/ATA 2016 990.pdf
       
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    25. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      http://otologicpharma.com/wp-conten..._Effects_of_Delayed_and_Extended_FRR_2011.pdf

      Fascinating article examining ANOTHER nitrone compound’s (4-OHPBN, not NHPN-1010) effects on acoustic trauma in adjunct therapy (antioxidants NAC + ALCAR).

      Another interesting passage about distribution of damage relative to the apex: “Large losses (about 70%) induced by noise were observed at 55–90% distance from the apex, indicating high frequency regions (2–10 kHz). The functional and morphological con- sequences of noise trauma were significantly attenu- ated by a combination of 4-OHPBN plus NAC plus ALCAR.”
       
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    26. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Dr. Kopke (from Hough) is an author on that paper, too.
       
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    27. mrbrightside614

      mrbrightside614 Member Podcast Patron Benefactor Advocate

      Location:
      NE Ohio, USA
      Tinnitus Since:
      July 2019
      Cause of Tinnitus:
      Acoustic trauma
      Nice catch! He produces absolutely fascinating research. I cannot express enough how thankful I am for people like @Justin De Moss and Dr. Kopke. True innovators and problem-solvers with altruistic motivation. We need more of them in this cold, Luddite-run world.

      I think it’s interesting they threw ALCAR into the mix considering my prior speculation regarding its potential utility in the hearing regeneration space. I still wouldn’t want to rock the boat and dose it concurrently with NHPN-1010 when that fateful day comes, though.
       
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    28. AVIYT
      Wishful

      AVIYT Member Benefactor

      Tinnitus Since:
      January 2019
      Cause of Tinnitus:
      Pregabalin
      Every bit helps, although more would be better. In comparison, the BTA is now giving out a grant worth up to £125,000 (= around $161,600 currently).
       
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    29. KyleM
      Sleepy

      KyleM Member

      Tinnitus Since:
      Aug 2018
      Cause of Tinnitus:
      Undetermined/Hearing Loss
      @Justin De Moss I'll take one magic pill please sir. To go. ;)

      I look forward to hopefully seeing more and more news from this topic.
       
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    30. annV
      Fine

      annV Member

      Tinnitus Since:
      2005
      Cause of Tinnitus:
      unknown - possibly hereditary
       
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