That makes sense that the damage to hair cells over time would be hypoxic pressure related injury (as well as reperfusion oxidative damage). Length of attacks is probably a big factor on how quickly it progresses (maybe more than frequency).
Otonomy OTO-413 — Treatment of Hidden Hearing Loss
- Thread starter Michael Larsen
- Start date
Member- May 16, 2017
- 3,754
- Tinnitus Since
- 04/2011
- Cause of Tinnitus
- Syringing + Somatic tinnitus from dental work
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
So bringing this thread back to OTO-413 and synapses... I think I'm going to go back to my daily high dose of dark cacao... I was doing it for 3 weeks and then stopped for a week after seeing improvement from CoQ10 - I can confirm that high-dose CoQ10 has improved my hyperacusis by 10-15%.
Apparently one needs to take dark cacao (95-100%) for 12 weeks to see an effect on synapse repair, although it's unknown whether this synapse repair would include those found in the cochlea.
Apparently one needs to take dark cacao (95-100%) for 12 weeks to see an effect on synapse repair, although it's unknown whether this synapse repair would include those found in the cochlea.
ajc
Member
- Feb 6, 2018
- 1,170
- Tinnitus Since
- 11/2002; spike 2009; worse 2017-18
- Cause of Tinnitus
- Loud music - noise damage
I use this one from Life Extension. It has Ubiquinol (better than ubiquinone, absorbs better), PQQ and Shilajit. These latter two apparently help boost the effect.
It doesn't do anything for my tinnitus though.
I've been taking CocoaVia and Lutein the past few weeks. So far haven't noticed a measurable difference, but it's still early. I bought a 12 week supply so I'm going to keep taking it until the end.
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
600mg typically, occasionally 400mg or 800mg. Bottle doesn't say if it's Ubiquinol or Ubiquinone.
The Chairman of Otonomy's Board of Directors dumped over a million shares yesterday. This is significant and possibly a bad sign because:
It's been in the back of my mind, but I'm wondering if they're just treading water right now waiting for those results to drop. If FX-322 shows potential for treating tinnitus, I'm thinking their game plan may be to liquidate the company and sell off the various tech. In such a scenario, Frequency Therapeutics may be able to pick up the extended release tech and maybe even the OTO-413 drug (though since they're focusing on progenitor cells they might not do that).
It may be too early for this kind of speculation, as they still may still have an ace up their sleeve, but the selling of shares seems like a bad sign.
- There hasn't been any insider trades in years.
- The stock price has recently cratered.
It's been in the back of my mind, but I'm wondering if they're just treading water right now waiting for those results to drop. If FX-322 shows potential for treating tinnitus, I'm thinking their game plan may be to liquidate the company and sell off the various tech. In such a scenario, Frequency Therapeutics may be able to pick up the extended release tech and maybe even the OTO-413 drug (though since they're focusing on progenitor cells they might not do that).
It may be too early for this kind of speculation, as they still may still have an ace up their sleeve, but the selling of shares seems like a bad sign.
Honestly, if Frequency Therapeutics buys Otonomy including OTO-413 I do hope Frequency Therapeutics will work on OTO-413 as well as it seems better at regrowing synapses compared to FX-322.
Another option is to mix both OTO-413 and FX-322 together and see if it can regrow both hair cells and synapses.
- Feb 14, 2020
- 1,630
- Tinnitus Since
- 1-2019
- Cause of Tinnitus
- 20+ Years of Live Music, Motorcycles, and Power Tools
Not likely. Frequency Therapeutics is going to keep investing in their PCA platform. They don't have the cash position to start acquiring. It would be more likely for an established drug maker to buy up the extended release gel & OTO-413 to get into the hearing market once FX-322 starts bringing in new investment. The release gel problem for FX-322 may be proprietary and Otonomy's formula ma not even work for FX-322.
I saw your post in the Frequency Therapeutics thread about the new job posting on their website. It sounds like they're working on a better gel and may not need Otonomy's tech.
I doubt it.
There are currently no drugs that treat tinnitus. Assuming a drug emerges that does treat it, for example, FX-322, there is still lots of room in the market for other drugs that also treat it, treat it differently, work better with different people or under different circumstances, work cumulatively, have different risk profiles, etc.
I agree in theory, but disagree in the case of these particular drugs. FX-322 generates new hair cells, it's basically a healing treatment. OTO-313 doesn't heal anything, and it would require that you keep getting the treatment every 3 months. There's the potential that FX-322 could "cure" tinnitus if someone's tinnitus is due to dead hair cells. OTO-313 can't cure tinnitus, it's shown only to reduce it, and so far only in people who've recently developed tinnitus. To me it looks like a vastly inferior option (assuming FX-322 works).
Though then again, I can concede that I may be wrong. FX-322 may not reduce tinnitus for everyone - and in that case, there would be room for OTO-313. Really it'll depend on what the data from Frequency Therapeutics' Phase 2a study shows.
Could you enlighten me on the effect of dark cocoa on synapse repair? I've googled it and searched the forum, but can't seem to find anything.
We've created the narrative that FX-322 "cures tinnitus," and hopefully it does, but at this point, that's the theory. In practice, it doesn't even exist yet in the marketplace.
More likely is that FX-322 helps some people some of the time to some extent, which is what the overwhelming majority of drugs do.
Drug companies put up websites showing happy couples in a field having a picnic, a golden retriever at their side, the sun shining. The message: this drug gave them their life back. Who would ever need another? Well, anyone for whom the drug is not a magic bullet, didn't work, partially worked, or had too many side effects. Which is why research and development for vexing medical problems doesn't stop just because one company announces a first generation drug, however promising it looks.
I don't think *anyone* here claimed this would help tinnitus for any other cause than hair cell loss. If you have some other cause, obviously, this wouldn't be a silver bullet.
Just like if ear wax was your cause, removing the wax would be your cure (or treating TMJ or middle ear disease or hydrops etc etc).
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
Not to be a pedantic grammar nazi, but I think people have hyped up as FX-322 as a treatment, not a cure. I think we will see a range of outcomes from FX-322 regarding tinnitus: full resolution of tinnitus, partial resolution of tinnitus (i.e. some tones disappear), reduction in perceived volume of tinnitus, and no change at all. In fact, it wouldn't surprise me if you saw some temporary cases of worsening while the brain reshuffles its neurons in response to new input. Furthermore, unresolved ear drum perforation from the injection could make tinnitus worse also.
ajc
Member
- Feb 6, 2018
- 1,170
- Tinnitus Since
- 11/2002; spike 2009; worse 2017-18
- Cause of Tinnitus
- Loud music - noise damage
There's no proof of FX-322 fully or partially resolving tinnitus for anyone. Anecdotes of improvement Carl LeBel mentioned could have been placebo. Theories about brain being stuck with tinnitus as time goes by could be correct, even if FGG always brings up phantom pain from amputated legs, tinnitus could be more insidious than that...
How will people who hoped FX-322 would resolve their tinnitus cope when it doesn't improve after all?
My advice is not to expect any improvement, but to be happy if you get any.
If it's stuck in the brain, people who had treatable causes wouldn't be able to treat it (e.g., ear wax, nutrient deficiencies, auto immune, hydrops, the list goes on...). I could be multi factorial on some people beyond just hair cells (you could have hair cell loss plus TTTS just to throw out an example) but "stuck in the brain" would mean tinnitus is the only example where neuroplasticity only works in one direction and we know from cochlear implant studies that's just not true.
- May 27, 2020
- 556
- Tinnitus Since
- 2007
- Cause of Tinnitus
- Loud music/headphones/concerts - Hyperacusis from motorbike
I think you are right to temper expectations and there has been perhaps a little too much hype regarding FX-322's potential to treat tinnitus. It is a hearing loss drug, after all. However, I don't think we should take anything away from the due diligence people on this forum have done in making some kind of informed guess as to what may happen.
We have seen many anecdotal cases of tinnitus improving in patients who receive cochlea implants and hearing aids, both of which are very crude pieces of technology, the implication being that there would appear to be some kind of relationship between loss of input and tinnitus. FX-322 is effectively a natural substitution for these devices, except it has the added benefit that it repairs the auditory system in a less crude way, because it repairs our natural human hearing. And of course, it is expected to bring an additional level of clarity in places where it also regrows synapses.
On top of all this, there have been studies in rodents showing that tinnitus has been prevented after noise exposure when hair cell loss has also been prevented when compared against controls. So I would say that although we don't have direct evidence for FX-322 directly, we can make a reasonable guess as to what it may be able to do if hair cells (and some synapses) are restored. There is evidence to suggest that tinnitus doesn't necessarily get "stuck" in the brain, so I would be incredibly surprised if Phase 2 results don't show some kind of improvement. If it doesn't, I think this would all but confirm that we really do need a synapse drug*, because synapses are the next peripheral point of failure in the human auditory signal chain.
*assuming FX-322 is able to reach lower frequencies.
I agree with all of this except I don't think it's going to end up being one structure for everyone. In some people it's synapse, in others it is hair cell. Basically, whatever interferes with auditory input. That's why tinnitus is very diverse in its causes.
I like to compare it to Horner's syndrome (it's not a perfect comparison but the gist helps). You can have a single lesion anywhere from your chest to your eye and still get Horner's symptoms because you are interfering with proper nerve signals. It depends on the individual.
Good to see everyone is still getting some exercise on the circular conversation treadmill. Enjoy your workout everybody!
"Tinnitus is correlated with loss of auditory input."
"But what if it's NOT."
"Tinnitus is correlated with loss of auditory input."
"But what if it's NOT."
You are absolutely right. Look at antidepressants. Triads of them on the market and they keep getting better.
- Feb 20, 2021
- 51
- Tinnitus Since
- 10/2019 (mild), 09/2020 (severe)
- Cause of Tinnitus
- SSHL
Probably not the right channel but: Is there already any consensus in the community as to whether NHPN-1010 (HPN-07 + NAC) has any ability to regrow synapses just as OTO-413 is supposed to have?
Jay Lichter, the founder of Otonomy and the Chairman of its board of directors, has sold all of his shares in the company over the last week:
https://investors.otonomy.com/node/9931/html
https://investors.otonomy.com/sec-filings
It really looks like he's bailing, like he's lost faith in the company. Either that or maybe he's just really upset that it will no longer have a drug for Ménière's (which he has).
https://investors.otonomy.com/node/9931/html
https://investors.otonomy.com/sec-filings
It really looks like he's bailing, like he's lost faith in the company. Either that or maybe he's just really upset that it will no longer have a drug for Ménière's (which he has).
I wonder what that means for OTO-413. Does Otonomy really have nothing in the pipeline now that their drugs have failed in the clinical trials.
This really sucks for Otonomy. I guess Frequency Therapeutics will be the only company that is ahead in the hearing loss regeneration game. I pray FX-322 will solve all our issues.
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