Otonomy OTO-313 — Treatment of Tinnitus

[star-affinity]

Losing a limb and losing hearing causes a lot less nerve activity not more.

I had to quote you on this since the research covered in this video seem to show quite the opposite when it comes to loss of auditory nerve fibers – flowchart at 35:39.



Noise exposure -> Loss of auditory nerve fibers -> Increase in central gain -> Tinnitus/Hyperacusis

So, while the loss of nerve connections might mean less nerve activity, it leads to "central gain" which I guess means the brain is "doing things" with this loss of input from the nerves that used to be there. I sure hope fixing those nerves will also mean the tinnitus stops. Hope this can be confirmed in research at some stage.

 

[PortugalTheMan]

Any news about the results of this drug?

 

[Nobody19]

Any news about the results of this drug?

Read the last 2-3 pages and you'll find everything you want to know. In short, the Phase 2 trial is currently running.

 

[Zugzug]

I had to quote you on this since the research covered in this video seem to show quite the opposite when it comes to loss of auditory nerve fibers – flowchart at 35:39.

Noise exposure -> Loss of auditory nerve fibers -> Increase in central gain -> Tinnitus/Hyperacusis

So, while the loss of nerve connections might mean less nerve activity, it leads to "central gain" which I guess means the brain is "doing things" with this loss of input from the nerves that used to be there. I sure hope fixing those nerves will also mean the tinnitus stops. Hope this can be confirmed in research at some stage.

What in the world are you talking about? I know @Contrast doesn't frequent here much, but here is the full post that he made. His entire post is about an increase in central gain. In fact, the whole point of his post was that he was skeptical of peripheral tinnitus as opposed to only central gain.

I disagree with this whole model of "acute peripheral tinnitus" and want evidence of it as I subscribe to a model that tinnitus is always central, never peripheral.

The only peripheral sensation is normal hearing just like the only peripheral sensation of having a limb is actually feeling a real limb that exist, amputating a limb or damaging an important nerve in it leading to a phantom sensation the limb is generated in the brain not the lost limb.Losing a limb and losing hearing causes a lot less nerve activity not more. The central gain mechanisms is heightened with peripheral activity is lowered.

People with phantom limb syndrome report feeling a weird small stump not actually the natural feeling of their limb, just like people with tinnitus don't report hearing voices or music just simple basic tonal noises. As far as I am concerned Auris Medical was wrong, OTO-313 is a copy of a mistake and tinnitus is always central and never peripheral.

Blocking NMDA prevents hair cell and ribbon synapse death and preventing hearing loss can prevent tinnitus, that's why it only works in an acute phase.

OTO-313 is an acute hearing loss agent, OTO-413 is a valid treatment for SNHL and tinnitus in the longterm.

 

[star-affinity]

What in the world are you talking about? I know @Contrast doesn't frequent here much, but here is the full post that he made. His entire post is about an increase in central gain. In fact, the whole point of his post was that he was skeptical of peripheral tinnitus as opposed to only central gain.

I don't know what I'm talking about.
I'm trying to figure stuff out. And you're right – @Contrast didn't say anything that contradicted what's said in that Stanford talk. I don't know how I was thinking. Maybe I still have trouble seeing the difference between peripheral and central tinnitus. But I think I get it now. Tinnitus being "central" means tinnitus is not really ever generated in the ear, since a loss of synapses means less nerve signals to the brain, which if anything should mean "quietness," not more sound in the form of tinnitus.

Sorry for my confusion. As long as we can fix the type of tinnitus that comes with a hearing loss by fixing the synapses I'd be happy, which seem to be something @Contrast also thinks OTO-413 can do.

I think my concern also was that I read about those situations where even cutting the auditory nerve didn't get rid of the person's tinnitus, but I take it that could be because the nerve signal from a working inner ear is still missing and the brain just keeps doing what it did when it was connected to the cochlea – fixing those broken/disconnected nerve fibers would be the only solution to stop the tinnitus. I guess/hope…

Edit:
Could it also be that damaged synapses/nerve fibers that gets disconnected from the hair cell start to "misfire" i.e. sending signals to the brain that corresponds to the frequencies to which those synapses used to get info from when connected to their hair cell? This would mean the tinnitus is peripheral, right?

I was just thinking about my latest high frequency tinnitus which I thinking corresponds to the frequencies where I also have hearing loss. Haven't confirmed that yet, though.

 

[Cernuto]

When you unplug a guitar cable from a guitar with the amplifier turned up, you'll hear a buzz. The end of the guitar cable is picking up noise. It acts as an antenna and the amplifier amplifies the noise picked up. I wonder if this is an analogy for tinnitus? I may be completely wrong.

 

[Piney]

When you unplug a guitar cable from a guitar with the amplifier turned up, you'll hear a buzz. The end of the guitar cable is picking up noise. It acts as an antenna and the amplifier amplifies the noise picked up. I wonder if this is an analogy for tinnitus? I may be completely wrong.

You may be completely right.

 

[PortugalTheMan]

Read the last 2-3 pages and you'll find everything you want to know. In short, the Phase 2 trial is currently running.

I was talking about the people who are taking part in the trial. I wanted to know if anyone had more news about if they are improving or not.

 

[Exit]

I was talking about the people who are taking part in the trial. I wanted to know if anyone had more news about if they are improving or not.

Give it a week's patience

 

[TrevorSanders]

I was talking about the people who are taking part in the trial. I wanted to know if anyone had more news about if they are improving or not.

I'm still debating if I should get the injection or not. I really can't risk my tinnitus worsening. What are your guys' opinions?

 

[canteven]

Excitedly waiting for results too!

 

[Exit]

I'm still debating if I should get the injection or not. I really can't risk my tinnitus worsening. What are your guys' opinions?

For you, the window of opportunity is here now since this probably won't help for long timers. I understand the fear and anxiety but in retrospect, in my case, I would do it.

If you're improving already, then maybe not...

 

[rei]

When you unplug a guitar cable from a guitar with the amplifier turned up, you'll hear a buzz. The end of the guitar cable is picking up noise. It acts as an antenna and the amplifier amplifies the noise picked up. I wonder if this is an analogy for tinnitus? I may be completely wrong.

I've had this same thought, that's why the whole idea of tinnitus being stuck in the brain doesn't seem right to me.

 

[patorjk]

I'm still debating if I should get the injection or not. I really can't risk my tinnitus worsening. What are your guys' opinions?

Go for it. If your tinnitus is less than 6 months old, it has a good chance of working. If it's older than a year I wouldn't bother (plus it could harm the study if people with tinnitus older than a year try to enter it).

Take a look at their latest presentation:

https://investors.otonomy.com/static-files/742c1d13-d0a2-4615-815a-9571ab41277c (slides 6-13)

The initial Phase 1 study showed a signal. The drug is gacyclidine + Otonomy's slow release gel. Gacyclidine was previously shown to have an effect in the paper titled "Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case series". If you checkout that paper you'll see charts on a hand full of case studies that were done.

 

[Gee82]

I'm still debating if I should get the injection or not. I really can't risk my tinnitus worsening. What are your guys' opinions?

Tinnitus is likely to get worse over time anyway; if I had a chance for a treatment now I would jump on it.

 

[aorelia]

Anyone in the trial with bilateral tinnitus and not just unilateral? I mentioned this to the clinic and they said there is still an opportunity for me to get in the trial.

 

[TrevorSanders]

Tinnitus is likely to get worse over time anyway; if I had a chance for a treatment now I would jump on it.

I've had my tinnitus for around 10 months and I've noticed that worsening trend already. I'm pretty positive I'm going to go through with it. I'll let y'all know how it goes when I get the injection on Thursday and the following weeks after.

 

[TrevorSanders]

Anyone in the trial with bilateral tinnitus and not just unilateral? I mentioned this to the clinic and they said there is still an opportunity for me to get in the trial.

That's interesting. They were pretty adamant about me making sure I only had ringing in one ear.

 

[Nobody19]

I was talking about the people who are taking part in the trial. I wanted to know if anyone had more news about if they are improving or not.

Ah oops, your post seemed to talk about the trial in general.

But I wouldn't put too much trust in these anecdotal posts. Let's hope the full results are good.

 

[ploughna]

I know it's only being tested for acute (<1 year) tinnitus, but do they have any clue as to whether it might be good for chronic cases? If not, it won't be much good for any of us on here if it eventually hits the market (although I know I'd be happy to give it a try regardless).

 

[tommyd87]

I know it's only being tested for acute (<1 year) tinnitus, but do they have any clue as to whether it might be good for chronic cases? If not, it won't be much good for any of us on here if it eventually hits the market (although I know I'd be happy to give it a try regardless).

That will be something that might get examined and evaluated potentially after this trial.

There tends to be every chance that if the treatment becomes beneficial for the acute cases and successfully completes trials, that it can then be tried on long term cases to see the benefit on them.

 

[scotty03874]

That's interesting. They were pretty adamant about me making sure I only had ringing in one ear.

7-22 is the big day that's exciting. Please keep us all posted...

 

[scotty03874]

I'm still debating if I should get the injection or not. I really can't risk my tinnitus worsening. What are your guys' opinions?

100% go for it. It's not going to make you worse!

 

[Exit]

I know it's only being tested for acute (<1 year) tinnitus, but do they have any clue as to whether it might be good for chronic cases? If not, it won't be much good for any of us on here if it eventually hits the market (although I know I'd be happy to give it a try regardless).

If it's a success, they'll have lots of resources and optimism about accelerating their research into their other drugs.

It will speed them up with 5 years on OTO-6XX and such!

 

[hopes]

OTO-313 won't be a cure for sure. But if it can help some people reducing their tinnitus level, I'll try it.

 

[Toby1972]

I get my first injection tomorrow morning and I'm leaving tonight to drive up to a hotel near the trial site so I don't have to face morning Charlotte traffic. Having a super low tinnitus day today which is weird but welcome. I'll keep y'all updated if anything miraculous or terrible happens. Also looking forward to hearing from some of the other people doing the trial.

Glad to finally be taking this next step on my tinnitus journey.

Hello Sentinel,

Any update from you, how are you doing?

 

[Sentinel]

Any update from you, how are you doing?

Tinnitus is fluctuating wildly. I'm horribly sick with what I suspect is COVID-19. Vomiting, joint pain, nightmares, pins and needles all over my skin, bad headaches.

Hopefully getting tested today. Tinnitus was so bad the other night it cut straight through my masking. On top of that I'm pretty depressed right now. Haven't eaten in two days since keeping food down is difficult.

I'm sorry to be so disappointing, my life is a mess right now but I'll keep you guys informed of any changes.

Thanks for reaching out.

 

[Lukee]

Tinnitus is fluctuating wildly. I'm horribly sick with what I suspect is COVID-19. Vomiting, joint pain, nightmares, pins and needles all over my skin, bad headaches.

Hopefully getting tested today. Tinnitus was so bad the other night it cut straight through my masking. On top of that I'm pretty depressed right now. Haven't eaten in two days since keeping food down is difficult.

I'm sorry to be so disappointing, my life is a mess right now but I'll keep you guys informed of any changes.

Thanks for reaching out.

Sorry to hear about this... get tested ASAP.

Are you vaxxed?

 

[Nobody19]

OTO-313 gives you COVID-19, confirmed!

Seriously, that's tough luck =( I wish you a speedy recovery.

 

[TrevorSanders]

Tinnitus is fluctuating wildly. I'm horribly sick with what I suspect is COVID-19. Vomiting, joint pain, nightmares, pins and needles all over my skin, bad headaches.

Hopefully getting tested today. Tinnitus was so bad the other night it cut straight through my masking. On top of that I'm pretty depressed right now. Haven't eaten in two days since keeping food down is difficult.

I'm sorry to be so disappointing, my life is a mess right now but I'll keep you guys informed of any changes.

Thanks for reaching out.

Jesus. This does not make me want to get the injection tomorrow.