Otonomy OTO-313 — Treatment of Tinnitus

Great News! Wishing you and Trevor the best. Thank you for your bravery. I hope it only continues to get better for you.

 

@Sentinel, how are you feeling today?

 

Tinnitus has since returned to baseline and stayed that way.

I'm fine I guess.

 

Well, it’s good news that you’re not having side effects or doing worse.

Let’s hope you got the real deal and it does something.

You have noise-induced tinnitus from a loud hobby or something...?

Wishing you a good day.

 

We need posts from others to assess if it works or not. Maybe you got the placebo.

 

No, this is all anecdotal. We need to wait for the trial results to know if it works.

 

Guns and music most probably.

 

I'm kind of answering myself here, but on the topic of the source for tinnitus being central (brain) or peripheral (inner ear), on the first page of this thread @Contrast says:

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

I.e. indicating that it is the brain that creates the tinnitus sound with no input from the inner ear.

However, this is what Otonomy says about tinnitus:

"Tinnitus is often caused by cochlear injury due to excessive noise, physical trauma, persistent ear infection or exposure to an ototoxic agent, leading to over-activation of auditory nerve fibers and the perception of noise in the absence of an external stimulus."

https://investors.otonomy.com/news-...ates-phase-2-clinical-trial-oto-313-tinnitus/

So it sure seems the inner ear is involved (good news for treatment possibilities).

Maybe it is damaged (not dead) nerve fibre that causes the tinnitus, whereas dead nerve fibers wouldn't cause tinnitus at all ("just" hearing problems) since there is no input to the brain? Again, this is just me guessing here.

At least it's comforting to see Otonomy listing problems in the inner ear as a (one) source for tinnitus. I guess they wouldn't be testing this drug if it would be unlikely treatment of the inner ear could reduce or eliminate tinnitus.

 

But OTO-313 doesn't do anything to restore hearing. It's like treating the symptoms but not the underlying problem. Even if it did get rid of tinnitus (which would be great), it wouldn't restore hearing clarity and address hidden hearing loss. OTO-413 and Pipeline Therapeutics' drugs appear much more promising as it focuses on reversing cochlear synaptopathy which would improve hearing clarity (word in noise) and as an incidental effect, reduce or eliminate tinnitus.

 

All those hearing loss treatments aren't even being tested for tinnitus & hyperacusis, how are you so sure they will help?

 

Because the regenerative treatments treat the underlying source of tinnitus which is most commonly damage to cochlear synapses, and sometimes from damage to hair cells or a combination of both.

See:

Hidden Hearing Loss: The Effects of Synaptopathy

 

That’s because there is an assumption that if you fix the underlying issues in the ear such as IHCs, OHCs and synapses then that should reduce tinnitus and hyperacusis.

We have no proof but once these drugs succeed in the clinical trials then we would know if these drugs work at reducing tinnitus and hyperacusis.

 

I’d rather have silence than constant sound if it was up to me. For people who have severe and profound hearing loss, it would take a drug or any miracle to reverse the hearing loss to gain sound. I see a tinnitus cure coming before hearing restoration. In the end I’d take any fix, let me know where it’s at.

 

There seems to be some confusion about peripheral vs central. Tinnitus can (rarely) be a central only issue. It can be a previous and permanent peripheral loss and a permanent (as long as the peripheral loss is there) central response. It can be be a previous and permanent peripheral loss and an ongoing inflammatory issue (usually at the synapses and NMDA receptor sites) combining for a central symptom.

Subjective, sensorineural tinnitus is clearly a central symptom, and surely, restoring lost peripheral input should greatly improve it, if not totally cure it with time. I'm sure there's variability based on the person. For example, brains that need perfect input may need a total restoration in peripheral input and a reduction in inflammation in order to cure tinnitus.

As far as what OTO-313 does, it is an NMDA receptor antagonist (so it reduces excitation). It is designed for acute cases because that's when receptor inflammation is the most likely to be an issue. However, it may work for chronic cases where the tinnitus is greatly impacted by inflammation.

I have a deep curiosity in what it will do for autoimmune-induced tinnitus (and maybe even loudness hyperacusis) because these diseases have chronic inflammation as a core driver of the disease.

 

Thanks for the explanation. It's just that there were mentions from @Hazel and others in the comments on the Otonomy Tinnitus Talk Podcast interview that eventually even fixing the damage in the cochlea (if that is the source for the tinnitus) might not be enough to get rid of the perception, since the brain (auditory cortex?) also needs a "fix" after the tinnitus has "settled" – whatever that means and how it happens I have no idea.

Fixing the brain to me seems more difficult than taking care of what's in the cochlea, so I hope a synapse and/or hair cell fix will be enough to get rid of the tinnitus.

 

They were wrong, fixing the issue fixes the symptoms.

 

Question about this since I am pretty new to the world of hyperacusis. Could there possibly be a brain calibration component on top of healing the damage? Sort of like how you can't go back to normal after having surgery to repair an injury and need to do physical therapy. I was wondering if you would need to slowly ease yourself back into sound to recalibrate your brain after the damage is healed as to not shock the system so to speak for the hyperacusis to be reduced.

 

Maybe, but first you need to fix the underlying issues. For example, tinnitus may reduce after getting these drugs injected in to you ear but may not get rid of it completely unless using something like Lenire after treatment.

 

Let’s just hope when we fix the ear, we fix/diminish tinnitus. Wish there was more funding for these ventures. ATA has raised 6 million in 4 decades; it’s inversely proportional to the ailment both in proportion and toll.

 

Great if that's the case!

But do you mean it has been confirmed?

 

Nothing is confirmed regarding tinnitus, as we all know...

But it sounds logical enough.

Cutting the auditory nerve won’t help.

A study showed people got tinnitus from earplugs. And it went away when they stopped using earplugs!

And all those people with stress-, neck- or just plain old earwax-induced tinnitus! Nearly 100% of those cases recover.

So why wouldn’t restoring hearing fix noise-induced tinnitus!

 

Yes of course. Assuming you have for example noise-induced hearing loss then regenerating the damaged synapses and/or hair cells would reverse the tinnitus as well. Although as @Zugzug pointed out tinnitus can also arise (rarely) as a central only issue in those situations it may not help. But for the vast majority of situations people have cochlear damage from external insults, and therefore regenerating the damaged cells would unsurprisingly correct the symptoms (tinnitus and loss of hearing and clarity perceptions, word recognition in loud environments).

 

Lol what?

Do you mean: ear infections from dirty earplugs or earwax buildup from using earplugs?

Just regularly used earplugs without any ill side effects surely have never been found to cause tinnitus, have they?

 

It was @GBB who posted that I believe.

Yes, a very small study, where participants had to use an earplug 24/7 in one ear for 2 weeks.

After 10 days or so 70 % reported tinnitus like symptoms.

It went away after they stopped using the earplug.

I just read a new post on Tinnitus Talk today, from a person who have had tinnitus for 30 years. Now he got hearing aids, and after he takes them off, his tinnitus is very minimal until next morning!

 

Justin, I think the important thing for everyone is to eliminate tinnitus, it doesn't matter if you hear perfectly if you have tinnitus and it doesn't matter if you don't hear well if you don't have tinnitus; that's what hearing aids are for.

 

Ohh ok... So I saw a study where they put people into a complete soundproof room and every single one of them experienced tinnitus. So earplugs don't actually cause tinnitus, imagine that...

 

See this is were I somewhat differ. I think we've all waited long enough and we want a regenerative therapy that will restore clarity perception, and hearing, and as an incidental effect of that, eliminate tinnitus. Frankly, I think we may enjoy the benefits of completely regenerating our hearing just as much as we would be happy to eliminate tinnitus.

Sure OTO-313 can provide relief by reducing or eliminating the symptom of cochlear damage from external insults, but for me that's enough. I want to see both, restoration of hearing quality, and as an incidental effect of restoring cochlear function and health, eliminating tinnitus.

I think things should be done the right way. But at least OTIC is doing this with OTO-413.

 

That's probably because these people had extremely mild damage to their cochlea such that tinnitus only appeared after prolonged periods of silence, that wouldn't be perceptible otherwise in day to day life. Someone who let's say has taken very good care of themselves, never forgot to wear earplugs at a club/concert or took ototoxic antibiotics, probably would not experience any tinnitus even wearing earplugs for two weeks.

 

Anything getting in the way of hearing can cause tinnitus.

 

These type of people don't exist from a practical standpoint. All people have some level of wear and tear in their cochleas, except for maybe a newborn baby. Enough deprivation of sound via the prolonged use of earplugs causes the brain to create the "phantom noise."