Hough Ear Institute's Hair Cell Regeneration Project

[serendipity1996]

No prob, the inner ear is a complicated place! No synaptopthy drug thus far regenerates A2 OHC fibers. This is because A2 fibers are extremely resilient to sound and ototoxic damage and don't degrade readily or easily. They also only comprise 5% of the nerve fiber total and don't influence "typical" hearing function so companies don't see much point in trying to regenerate something that is:
1. Likely not damaged in the first place
and
2. Won't improve audiogram or word scores

For those with noxacusis the problem isn't that the A2 nerve fibers are damaged but that they are consistently being stimulated by ATP leakage, generating pain. The current theory is that this can be addressed by restoring OHC to prevent ATP leakage or by using a kv7 channel modulator such as what Dr. Thanos is working on for tinnitus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664349/#idm139719422741808title

However if you do have missing A2 nerve fibers Chen has stated in an email to me that they regenerated both using his method of DNA reprogramming. But this is because they were working with an entirely flat epithelium. Most of us are no where near that point.

Aha, yep I see where you're coming from now. I read this paper and speculated as much - that the problem isn't damage to the nerve fibers themselves but to the OHCs to which they are connected and then the fibres are implicated because they signal damage but I just wasn't entirely sure. That makes sense and is somewhat reassuring to hear!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664349/
Also something that I find reassuring is that for most of us, whilst we have some degree of noise trauma/damage to the inner ear we still have a good degree of hearing function etc and so we already have the existing inner ear architecture etc. So maybe that means repair is more straightforward.

 

[Buzzy1]

No prob, the inner ear is a complicated place! No synaptopthy drug thus far regenerates A2 OHC fibers. This is because A2 fibers are extremely resilient to sound and ototoxic damage and don't degrade readily or easily. They also only comprise 5% of the nerve fiber total and don't influence "typical" hearing function so companies don't see much point in trying to regenerate something that is:
1. Likely not damaged in the first place
and
2. Won't improve audiogram or word scores

For those with noxacusis the problem isn't that the A2 nerve fibers are damaged but that they are consistently being stimulated by ATP leakage, generating pain. The current theory is that this can be addressed by restoring OHC to prevent ATP leakage or by using a kv7 channel modulator such as what Dr. Thanos is working on for tinnitus.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664349/#idm139719422741808title

However if you do have missing A2 nerve fibers Chen has stated in an email to me that they regenerated both using his method of DNA reprogramming. But this is because they were working with an entirely flat epithelium. Most of us are no where near that point.

Hi, I'm really confused. Is there a simple way of explaining this? Will it be able to help people like me who have had t for a long time, in my case 38 years? Originally started from ear infection, but worse now due to hearing loss.
Thanks for any info you can give me.

 

[mrbrightside614]

Hi, I'm really confused. Is there a simple way of explaining this? Will it be able to help people like me who have had t for a long time, in my case 38 years? Originally started from ear infection, but worse now due to hearing loss.
Thanks for any info you can give me.

Basically, yes. HPN-07 (Hough pill) combined with N-acetylcysteine showed effectiveness in rescuing auditory nerve fibers outside of the immediate window... "Permanent threshold shift was established by open field blast insult. Treatment was initiated at 4 weeks post-injury,with HPN-07 plus NAC dosed at 300 mg/kg twice daily for 14 days. ABR threshold improvements were shown 14 weeks post-injury (8 weeks post-treatment) versus pre-treatment.

FIG. 29 shows NHPN-1010 treatment (HPN-07 plus NAC) restored IHC ribbon synapse numbers in established, chronic hearing loss model. NHPN-1010 treatment was initiated 4 weeks after injury and dosed daily for 14 days. Ribbon synapse counts were significantly restored 8 weeks post-injury."

The huge hurdle here is funding, and then admission to phase 2(?)

 

[mrbrightside614]

Exactly... same here... 20 years ago there was nothing. I was lucky that after 4 years my tinnitus basically disappeared.

Not to hijack (you can PM me and I can delete this post), but if you wouldn't mind telling the cause, severity, and if it just gradually diminished over time?

 

[Buzzy1]

Thank you, still quite complicated tho or I'm having a blonde moment.
Let's hope they get the funding after 38 years I could do with a break!

 

[serendipity1996]

Thank you, still quite complicated tho or I'm having a blonde moment.
Let's hope they get the funding after 38 years I could do with a break!

We will probably find out more in the podcast that will be conducted soon!

 

[HootOwl]

Hi, I'm really confused. Is there a simple way of explaining this? Will it be able to help people like me who have had t for a long time, in my case 38 years? Originally started from ear infection, but worse now due to hearing loss.
Thanks for any info you can give me.

The simple short answer is maybe :/

Sorry, I wish we could say for sure but we cant without knowing what structure is damaged inside the ear. Could be synapses, nerve fibers, OHC, IHC, or a combination of all of them.

Some people will see benefit from the pill, some won't. But if the pill doesn't work there are many other avenues of treatment coming up. I firmly agree with brokensoul that if your tinnitus is generated from cochlear damage then relief is coming in one form or another.

Many of us will likely need more than one piece of the regenerative puzzle though.

 

[Buzzy1]

@HootOwl
Thank you for taking the time to reply. I guess it's a waiting game, hopefully not too much longer. Had this since I was 23 and I'm now 61, would really like to hear silence or a quieter tinnitus.
Fingers crossed for all of us.

 

[serendipity1996]

Man, I really hope that some combination of hair/cell synaptic regeneration would help cure hyperacusis. My main worry is whether hyperacusis (specifically noxacusis) if it's a form of neuropathic pain could become centralised over time. I recall reading a post someone made on the forums touching on this a while back. Therefore would solving the damage at the original site (ie damaged OHCs) end up being a full solution. I guess there's still so much to uncover but only time will tell.

 

[mrbrightside614]

The simple short answer is maybe :/

Sorry, I wish we could say for sure but we cant without knowing what structure is damaged inside the ear. Could be synapses, nerve fibers, OHC, IHC, or a combination of all of them.

Some people will see benefit from the pill, some won't. But if the pill doesn't work there are many other avenues of treatment coming up. I firmly agree with brokensoul that if your tinnitus is generated from cochlear damage then relief is coming in one form or another.

Many of us will likely need more than one piece of the regenerative puzzle though.

Yeah I'd bank on this for acute phases and sub-chronic phases mostly. Although they've shown efficacy in the regeneration space, I wouldn't rely on a potent antioxidant in chronic cases—there, I'd expect (mostly) FX-322 and possibly OTO-413/PIPE-505 (if speech-in-noise is the primary problem) to be the primary treatment. Could give a shit less about the procedures, shoot me up. But it'd still be great knowing you could go to your doctor if and get a (pricey) pill in the likely event docs are negligent and don't refer you to immediate dexamethasone injection/high dose oral steroid upon tinnitus presentation.

I know you know this (and way more) haha just wanted to qualify my opinion of "basically yes"

 

[mrbrightside614]

Man, I really hope that some combination of hair/cell synaptic regeneration would help cure hyperacusis. My main worry is whether hyperacusis (specifically noxacusis) if it's a form of neuropathic pain could become centralised over time. I recall reading a post someone made on the forums touching on this a while back. Therefore would solving the damage at the original site (ie damaged OHCs) end up being a full solution. I guess there's still so much to uncover but only time will tell.

I really, really think this is unlikely. I'm not well read on hyperacusis at all but the likelihood that tinnitus becomes centralized (which I don't believe) is infinitely more viable than hyper/noxacusis becoming centralized. I've dealt with chronic pain twice separately, for about two years each time, and those experiences have anecdotally proven to me that the signal either gets down regulated over time, or I've habituated to it.

 

[Hazel]

Hey folks, good news: Today we finally managed to get the recording with Hough Ear Institute done!

I spoke with Dr. Rick Kopke and Justin DeMoss. They were very forthcoming, and also announced some quite exciting news from their side, although I can't yet reveal what it is.

I would like to specifically mention here how patient and persistant the Hough guys have been while we struggled with multiple technical issues before we finally were able to succesfully record. It just shows how serious they are about communicating directly with the tinnitus community.

We'll be editing over the next week and hope to publish in 1-2 weeks.

 

[HootOwl]

They were very forthcoming, and also announced some quite exciting news from their side, although I can't yet reveal what it is.

Really hope it's the much awaited phase 2 announcement.

 

[Rb86]

Thank you Hazel.

 

[Chriscom]

Hey folks, good news: Today we finally managed to get the recording with Hough Ear Institute done!

I spoke with Dr. Rick Kopke and Justin DeMoss. They were very forthcoming, and also announced some quite exciting news from their side, although I can't yet reveal what it is.

I would like to specifically mention here how patient and persistant the Hough guys have been while we struggled with multiple technical issues before we finally were able to succesfully record. It just shows how serious they are about communicating directly with the tinnitus community.

We'll be editing over the next week and hope to publish in 1-2 weeks.

That's great!

I would like to specifically mention here how patient and persistent the Tinnitus Talk team has been while struggling with multiple technical issues. Thank you!

 

[Markku]

If all goes as planned, the Hough Ear Institute interview will be published late tonight (GMT time). Or tomorrow the latest.

We want to get this out as soon as possible, so the transcript will be ready later (approx. a week from now).

Again I want to remind that numerous hours have gone into the planning, organizing and production of this interview as well as all our other interviews, from our all-volunteer team (me, @Hazel, @Autumnly, @Liz Windsor).

So if you'd like to show your appreciation starting at a modest $2/month level of Patreon support, please do so now by clicking the below image (did you know that I, Hazel and Autumnly all are Patreons of Tinnitus Talk Podcast ourselves, besides also volunteering our spare time?):

In the future we'll have Patreon-only bonus content too...

 

[mrbrightside614]

If all goes as planned, the Hough Ear Institute interview will be published late tonight (GMT time). Or tomorrow the latest.

We want to get this out as soon as possible, so the transcript will be ready later (approx. a week from now).

Again I want to remind that numerous hours have gone into the planning, organizing and production of this interview as well as all our other interviews, from our all-volunteer team (me, @Hazel, @Autumnly, @Liz Windsor).

So if you'd like to show your appreciation starting at a modest $2/month level of Patreon support, please do so now by clicking the below image (did you know that I, Hazel and Autumnly all are Patreons of Tinnitus Talk Podcast ourselves, besides also volunteering our spare time?):

In the future we'll have Patreon-only bonus content too...

View attachment 35812

I'm in. Is JimH still matching donations or was that only for the Vancouver trip?

 

[Coleoptere]

@Markku, @Hazel, @Autumnly, @Liz Windsor thank you so much for making this happen!

 

[Hazel]

Hi there,

Well, the episode is out, in record time!

Hough put out a press release earlier today about their new partnership, which is discussed in the episode.

Tell us your thoughts!

 

[FGG]

Just listened to the podcast. Very interesting. But I am a bit confused after reading the official press on this:

https://www.prnewswire.com/news-rel...hough-ear-institute-scientists-301003204.html

It looks like the initial phase 2 isn't looking at tinnitus or speech in noise. How exactly are they accessing synapse regrowth clinically then? Or is the first phase 2 just going to be post acute noise exposure and looking at audiograms?

Maybe this was answered somehow and I didn't hear it right. I will check the transcript when it comes out.

 

[Hazel]

It looks like the initial phase 2 isn't looking at tinnitus or speech in noise. How exactly are they accessing synapse regrowth clinically then? Or is the first phase 2 just going to be post acute noise exposure and looking at audiograms?

The drug will be marketed for hearing loss, not for tinnitus specifically (at least not initially). This means that the phase 2 clinical trial has to assess efficacy for hearing loss. How exactly they plan to assess outcomes I don't know, but audiograms would seem likely. I believe they plan to do a follow-up study looking specifically at outcomes for tinnitus.

 

[Momme]

Is it for chronic tinntius? And for all tinnitus?

 

[FGG]

The drug will be marketed for hearing loss, not for tinnitus specifically (at least not initially). This means that the phase 2 clinical trial has to assess efficacy for hearing loss. How exactly they plan to assess outcomes I don't know, but audiograms would seem likely. I believe they plan to do a follow-up study looking specifically at outcomes for tinnitus.

So trial participants will have abnormal audiograms then? Because if they were looking at cochlear synaptopathy, shouldn't Speech in Noise be included? So it seems that in this first phase 2 they are looking at audiograms?

If that were the case they are looking for participants with acute damage and acute audiogram changes then right? Because it doesn't regrow hair cells.

 

[Lucifer]

I haven't listened to the podcast as I need the transcript.

Did it state when they are starting Phase 2 and when they will finish it?

 

[FGG]

I haven't listened to the podcast as I need the transcript.

Did it state when they are starting Phase 2 and when they will finish it?

They said they expect the first phase 2 (it is implied there will be more than one phase 2 I thought) to begin in 2020 and the drug to be out mid decade. They aren't testing this on tinnitus patients in this next phase but hope to later.

 

[Hazel]

So trial participants will have abnormal audiograms then? Because if they were looking at cochlear synaptopathy, shouldn't Speech in Noise be included? So it seems that in this first phase 2 they are looking at audiograms?

If that were the case they are looking for participants with acute damage and acute audiogram changes then right? Because it doesn't regrow hair cells.

Indeed it doesn't regrow hair cells, but repairs damaged nerves. But to be honest we didn't go into detail on the design of the phase 2 trial, and I don't know if there is a design yet. Perhaps @Justin De Moss can shed some more light here.

 

[FGG]

Is it for chronic tinntius? And for all tinnitus?

They said for they saw evidence for noise induced but that's also the only etiology they tested I think. They believe it will help chronic cases but are going to do more pre-clinical testing soon to confirm.

 

[FGG]

One point I want to highlight is Dr. Kopke believes fixing the cochlea will result in treating tinnitus. He doesn't believe it's "stuck in the brain" and he uses his 1/2 to 2/3 of tinnitus patients with hearing loss improving even with just hearing aids as further evidence of this.

 

[Lucifer]

Indeed it doesn't regrow hair cells, but repairs damaged nerves. But to be honest we didn't go into detail on the design of the phase 2 trial, and I don't know if there is a design yet. Perhaps @Justin De Moss can shed some more light here.

That's interesting. If FX-322 doesn't solve all of our problems we might need a combination of FX-322 and HEI Pill.

 

[serendipity1996]

This is so exciting. Did they mention whether this might help hyperacusis?