Otonomy OTO-413 — Treatment of Hidden Hearing Loss

Discussion in 'Research News' started by Michael Larsen, Jan 9, 2018.

    1. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

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      Here is something on the neurite outgrowth caused by the drug:

      http://otologicpharma.com/the-science/

      I remember that the neurites did reportedly synapse and the rodents were tested for this weeks later. @HootOwl, do you remember where that info is by any chance?
       
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    2. spacehunter

      spacehunter Member Benefactor

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      Thank you very much for the reply!

      auditory-neurons-jpg-300x107.jpg

      I really like how they show the comparison between BDNF (OTO-413) and HPN-07. If HPN-07 (+NAC) really has the same effectiveness (provided the concentration is adapted correctly) as BDNF, this great news.
       
    3. Street Novelist
      Depressed

      Street Novelist Member

      Location:
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      February 2018
      Cause of Tinnitus:
      Listening to loud music through headphones
      So, OTO-413 could restore hearing, even if it doesn't regrow the hair cells? Might simply repairing the synapses be enough?
       
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    4. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

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      Synapses are a component of hearing, most involved in "speech in noise" hearing. The "whether that's enough" likely depends on the individual.
       
    5. Jim Vasilakis

      Jim Vasilakis Member

      Tinnitus Since:
      2020
      Cause of Tinnitus:
      Loud Noise
      How can someone find out if they have hidden hearing loss?
       
    6. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

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      There isn't a good audiological test for synaptopathy, unfortunately. If you have it widespread enough in the most important speech frequencies, however, you will have difficulty hearing in noisy places (aka "speech in noise difficulty").
       
    7. Justin Mills

      Justin Mills Member

      Tinnitus Since:
      2 year
      Cause of Tinnitus:
      loud music
      According to the latest research it is not so much the destruction of sound receptor hair cells, rather it is damage to cochlear synapses (which in turns causes progressive auditory nerve degeneration) that is the most significant cause of both tinnitus and loss of sound clarity perception.

      Hidden Hearing Loss: The Effects of Synaptopathy


      The only regenerative therapy I've seen targeting auditory synapses is OTO-413. The problem is Otonomy appears to be specifically trying to exclude tinnitus from its endpoints.

      See:

      OTO-413 in Subjects With Speech-in-Noise Hearing Impairment

      "Exclusion Criteria: Subject self-reports bothersome, subjective tinnitus and is consistently aware of their tinnitus throughout much of the waking day."

      It's like Otonomy despite having so many neurotology experts doesn't realized that hearing loss and tinnitus are integrally connected. We know that tinnitus is usually caused by auditory damage from external sources such as noise or drugs. Reversing the damage through regenerative treatments would thus also reverse the tinnitus. Yet it appears they are excluding the group that would most be helped by OTO-413, people who are "consistently aware of their tinnitus" all day.

      Perhaps if OTO-413 is approved for "hidden" hearing loss, it can nonetheless less be used off-label for tinnitus. It would've been better however seeing them state up front that it's for both tinnitus and hearing loss.

      Another note, it would be great to see companies begin trying a treatment that includes both regeneration of the synapses and hair cells. All of the drugs in being studied either focus only on restoring hair cells (FX-322 progenitor cell stimulating small molecule) or regenerating synapses, OTO-413. It seems self evident that doing both would be the most effective. Such an approach is also more likely to get approved as a treatment because it would most likely yield clinically significant improvements.
       
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    8. Tezcatlipoca
      Question it

      Tezcatlipoca Member

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      First, they'd need to find a drug that does both well. IMO this is a non-issue.

      If the drugs get approved, we can get both. If they don't, well then the whole argument is a moot point because we wouldn't be able to get them anyway.
       
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    9. serendipity1996
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      serendipity1996 Member Podcast Patron Hall of Fame

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      Otonomy is not the only company working on synapse regeneration - Pipeline Therapeutics also has a drug in clinical trials targeting this.

      Otonomy also has a hair cell drug in development - I assume it will be a few years at least until they advance to clinical but they are working on both.

      Regarding targeting both, I am not sure what you mean - do you mean a single drug that does both at the same time? Frequency Therapeutics have demonstrated that when you regenerate a hair cell, it automatically then synapses to the auditory nerve. Robert Jackler from the Stanford Initiative to Cure Hearing Loss also demonstrated this back in 2012. Also, many people have synaptopathy without corresponding hair cell loss so a treatment targeting solely synaptopathy will be greatly valuable.

      Also, thanks for linking the talk! Gonna watch it.
       
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    10. Street Novelist
      Depressed

      Street Novelist Member

      Location:
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      Cause of Tinnitus:
      Listening to loud music through headphones
      PIPE-505 regrows synapses as well. Don't forget about that one. Their results come out next month.
       
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    11. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

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      I found 27:30 on to be extremely interesting, and telling... Especially that part about the audiogram...
       
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    12. Tezcatlipoca
      Question it

      Tezcatlipoca Member

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      Scientists have begun acknowledging our "wild theories" about the audiogram.

      Who would have thought a century old test was flawed...
       
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    13. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

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      LOL... the "wild theories" are based on scientific research findings that members read and relayed. I think it's more the members here that need to acknowledge the science behind hearing is more than 9 tones on a sheet.

      It blows my mind that hearing assessments developed from 1940-1960 are considered "standard."
       
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    14. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
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      Yeah it's definitely not "wild theories," I was just paraphrasing what some users have said.

      I think it's akin to flat earth in a way, science is very complicated so people want to simplify it as much as they can so they feel like they "get it," and 9 tones on a piece of paper is pretty simple!

      Now the real question is, does the FDA consider this "wild theories"? A lot of hearing loss drugs would have way better chances if the FDA reviewers took the audiogram with a grain (or maybe more like a pinch) of salt.
       
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    15. newfie
      Spaced

      newfie Member

      Location:
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      10/2007
      Cause of Tinnitus:
      Acoustic trauma (gun)
      I have a near perfect audiogram, ABR, conduction test, OHC etc... but have had very tinny, crackly distorted hearing in my right ear and moderate-severe tinnitus since a couple of gun sessions. I can't hear anything clearly in my right ear in restaurants, schools, loud places. Dishes, toilets, kids voices, shrill dog barks, shower faucets... all extremely distorted.

      I highly suspect I suffer from cochlear synaptopathy and I am very hopeful that OTO-413 is successful. It could give some of us relief. Only if you live with hidden hearing loss, do you know the frustration of having to live with it daily and then having audiologists tell you "your audiogram is perfect, you don't have any hearing loss."

      Hidden Hearing Loss: M. Charles Liberman PhD
       
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    16. GBB

      GBB Member Hall of Fame

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      I trust my ENT - he hits my knee with a little hammer and my leg kicks - means my nervous system is MINT. After that we did a high five and skipped the audiogram altogether. This is good old American healthcare just like what Patton got and by god I'm a patriot.
       
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    17. Lukee

      Lukee Member

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      GBB: Americans have bad healthcare.

      CANADA: Hold my beer...
       
    18. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

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    19. newfie
      Spaced

      newfie Member

      Location:
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    20. Tezcatlipoca
      Question it

      Tezcatlipoca Member

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      2022 is going to be a make or break year for Otonomy.
       
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    21. Rajin

      Rajin Member Benefactor

      Location:
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      Hearing loss ,noise
      Why do you say that? Will they come thru?
       
    22. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

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      Big fan of this urgency & new entry we’re seeing in the hearing space lately.

      Breakthroughs are coming...
       
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    23. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

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      The graphs on page 8 of the OTO-313 performance are interesting. All of the placebos clearly lowered their TFI as well. The placebo effect is real, apparently.

      Slide 11 also reveals a parallel to FX-322 concepts, which is that higher starting TFI help to reduce a floor effect.

      I think OTO-313 could be a nice drug. It might actually help my problems some.
       
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    24. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
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      Definitely. They see the writing on the wall and know it's just a matter of time. Everyone is rushing to be the first to make the big break in the hearing space and make a ridiculous amount of money.
       
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