Hough Ear Institute's Hair Cell Regeneration Project

[FGG]

@brokensoul, this study seems to imply that EEG changes occur only with tinnitus distress and not having tinnitus. I.e. mild tinnitus did not show changes. Do we know if rodents have tinnitus distress?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364116/

Also, interestingly, if I am reading this right they found that the brain changes associated with tinnitus in this study occurred with hearing loss over 8000 Hz (and only in those higher frequencies) and that the hearing loss itself may account for those changes.

 

[Mentos]

@Mentos

When you say the treatment repairs nerve endings, are you talking about the auditory nerve?

That's my understanding that auditory nerve endings and synapses should be repaired, but better to ask @Justin De Moss.

 

[Mentos]

@brokensoul, this study seems to imply that EEG changes occur only with tinnitus distress and not having tinnitus. I.e. mild tinnitus did not show changes. Do we know if rodents have tinnitus distress?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364116/

Based on what I was informed by brai3n.com who analyzed my qEEG it's not distress alone, I have it mild and consider myself quite habituated, still the qEEG indicates I have tinnitus.

 

[HootOwl]

Like I say, if you get FDA approval for the cochlear implant trauma, you will very quickly have the tinnitus community buying this pill and letting you know if it works or not.

People somehow got their hands on Trobalt (which had far more serious side effects) so I'm confident most doctors would feel safe providing this off label since it's just a potent anti-oxidant.

I've already asked a few and they said if the phase 1 data showed it was safe they have no issue.

After reading the press release and reevaluating the current state of the pill, I'd rather get this thing to market sooner than draw out the approval process by having a phase 2b for tinnitus. Unless that phase 2b ran concurrently with phase 3 for the cochlear implant trauma. Otherwise - let's just assume it is effective for acute cases and the chronic cases can asses efficacy once it can bought.

 

[Hazel]

Hey folks, the transcript of the podcast is now available!

 

[brokensoul]

@brokensoul, this study seems to imply that EEG changes occur only with tinnitus distress and not having tinnitus. I.e. mild tinnitus did not show changes. Do we know if rodents have tinnitus distress?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364116/

Also, interestingly, if I am reading this right they found that the brain changes associated with tinnitus in this study occurred with hearing loss over 8000 Hz (and only in those higher frequencies) and that the hearing loss itself may account for those changes.

I just went to Brai3n (Dr. De Ridder) and they did a Loretta qEEG test (with eyes closed and ear protection). Afterwards they showed me the results and it contained a brain image with 1) hyperactive auditory cortices and 2) another zone that was underactive.

It also confirmed brain wave anomalies (alpha, beta, gamma and delta band anomalies). I don't know if this is common for tinnitus. Perhaps the severity of the anomalies is related to VSS. My tinnitus is also not mild.

It's probably not the most sensitive test you can do. It's fairly basic as far as I know.

 

[brokensoul]

I just went to Brai3n (Dr. De Ridder) and they did a Loretta qEEG test (with eyes closed and ear protection). Afterwards they showed me the results and it contained a brain image with 1) hyperactive auditory cortices and 2) another zone that was underactive.

It also confirmed brain wave anomalies (alpha, beta, gamma and delta band anomalies). I don't know if this is common for tinnitus. Perhaps the severity of the anomalies is related to VSS. My tinnitus is also not mild.

It's probably not the most sensitive test you can do. It's fairly basic as far as I know.

Just want to add that it also included functional connectivity results (brain regions that communicate which each other). It's the test which shows red lines for communicating regions. The report also contained signal generation by several brain regions (don't recall what it is called) and this demonstrated that I have thalamocortical dysrhytmia. The strength of the signal was too low or deviated significantly from the norm. It's like an electrical pulse, but my pulses are abnormal. This is what I correlate with the weird feeling I have in my brain.

I have asked this question before, but never got an answer. Is there anyone who has done such a test with similar results, but only has tinnitus (and not VSS)?

@Mentos, what were your results?

 

[Mentos]

Just want to add that it also included functional connectivity results (brain regions that communicate which each other). It's the test which shows red lines for communicating regions. The report also contained signal generation by several brain regions (don't recall what it is called) and this demonstrated that I have thalamocortical dysrhytmia. The strength of the signal was too low or deviated significantly from the norm. It's like an electrical pulse, but my pulses are abnormal. This is what I correlate with the weird feeling I have in my brain.

I have asked this question before, but never got an answer. Is there anyone who has done such a test with similar results, but only has tinnitus (and not VSS)?

@Mentos, what were your results?

More or less same as yours. I have only tinnitus. No visual snow.

 

[brokensoul]

More or less same as yours. I have only tinnitus. No visual snow.

Did Dr. De Ridder tell you that you have thalamocortical dysrhythmia?

 

[Mentos]

Did Dr. De Ridder tell you that you have thalamocortical dysrhythmia?

It was Jan Ost I talked to via Skype, I don't think he mentioned thalamocortical dysrhythmia.

 

[Momme]

Did Dr. De Ridder tell you that you have thalamocortical dysrhythmia?

How do you get that? Thru noise induced or something else?

 

[brokensoul]

How do you get that? Thru noise induced or something else?

Tinnitus has been described as a thalamocortical dysrhythmia of the auditory pathway.

Visual Snow Syndrome has been described as a thalamocortical dysrhythmia of the visual pathway, but this syndrome usually includes tinnitus as well for most people with VSS, so in reality it's a thalamocortical dysrhythmia of the visual and auditory pathway.

The qEEG done by the Brai3n clinic in Belgium confirmed this for me, although this was not really discussed.

https://en.m.wikipedia.org/wiki/Thalamocortical_dysrhythmia

Thalamocortical Dysrhythmia: A Theoretical Update in Tinnitus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460809/

I have no idea what caused my condition.

 

[FGG]

Tinnitus has been described as a thalamocortical dysrhythmia of the auditory pathway.

Visual Snow Syndrome has been described as a thalamocortical dysrhythmia of the visual pathway, but this syndrome usually includes tinnitus as well for most people with VSS, so in reality it's a thalamocortical dysrhythmia of the visual and auditory pathway.

The qEEG done by the Brai3n clinic in Belgium confirmed this for me, although this was not really discussed.

https://en.m.wikipedia.org/wiki/Thalamocortical_dysrhythmia

Thalamocortical Dysrhythmia: A Theoretical Update in Tinnitus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460809/

I have no idea what caused my condition.

Forgive me if this is too off-topic but...

What Neuro transmitters does he propose are involved in this dysrhythmia? There may actually be a way to treat this pharmacologically.

There is (was? He was very old a decade and a half ago) a Nobel prize for medicine nominated doctor in Venezuela named Fuad Lechin whose life's work involved measuring serial levels of serotonin, Norepinephrine, Epinephrine and Dopamine etc at rest, orthostasis, light exercise, etc. and then figuring out how to pharmacologically tweak these levels to affect brain function and dysfunction, immune function (most people do not think the brain influences the immune system directly but he has shown that it does), etc.

I don't know if it's still the case, but he was once the only one in the world to treat people at a clinical/hospital level with this approach (it took very precise dosing).

I have his book. It's called Neurocircuitry and Neuroautonomic Disorders and he uses neurotransmitter tweaking to shift the immune system from TH-1 to TH-2 or vice versa. What's especially interesting here is he has profiles for "uncoping stress" and "endogenous depression" too. Since stress alone can, in some cases, lead to VSS, I wonder if this approach could help.

Worth nothing that he didn't mention the thalamus specifically in his book but I will include a photo below of the kinds of trends he saw in those measurements.

When I was there in 2004 (long story), he was training some German doctors in his method and i wonder if there would be a way to find them and ask them if something like this could help. This is super left field I realize but if VSS is truly a result of brain dysregulation in some cases (esp in those who have no cochlear damage), perhaps it can be treated as such.

 

[Justin De Moss]

What I'm saying is FX-322 has the experimental arm that would cost you guys $735k for testing specifically for tinnitus—this would suggest that a separate arm is required to have insurance approval for only tinnitus-related claims, right?

Not sure what you mean by separate arm. If you are talking about a wholly-owned subsidiary - then possibly, but it is usually by drug NOT indication.

 

[mrbrightside614]

Not sure what you mean by separate arm. If you are talking about a wholly-owned subsidiary - then possibly, but it is usually by drug NOT indication.

I mean they are testing the efficacy of FX-322 on hearing loss in one part of phase 2, and its effects on tinnitus on another population during phase 2.

What I'm saying is, you would need $735k to do the same, in opening up a phase 2 experiment that separately analyzed its efficacy in treating a tinnitus population.

 

[Justin De Moss]

This injection tech seems most similar to Regain, and somewhat similar to FX-322 except the latter actually duplicates the support cell in addition to creating an active hair cell. Both of these drugs are in phase 2 and, with FX-322 being fast tracked, will reach the market much quicker than even the pill will.

It's great that so much research is being done! That increases the odds of a solution making it to the market!

 

[FGG]

I mean they are testing the efficacy of FX-322 on hearing loss in one part of phase 2, and its effects on tinnitus on another population during phase 2.

What I'm saying is, you would need $735k to do the same, in opening up phase 2 separately devoted to studying its efficacy in a tinnitus population.

Just to clarify, FX-322 are testing it on the same population as an "experimental arm" addition in phase 2 to their original study.

 

[Justin De Moss]

Sorry, I meant to ask whether or not it can stop/reduce progression.

Depends. If the reason is related to nerve damage due to accumulated trauma over the years - yes. If it is related to hair cell damage in the cochlea - then the pill won't but the injection we are working on will.

 

[Justin De Moss]

Hi @Justin De Moss

My t started with an ear infection, but it is getting worse now due to hearing loss.

Is there any information you can give me about the injection? I thought the pill was for age-related hearing loss as well. It's all very confusing, is there a link I can go to for more information?

Thank you

The injection is still in pre-clinical studies. It is ready for a Phase I clinical study. Once we get it funded we will proceed. Most age-related hearing loss is due to hair cell damage (the injection), but if it is due to nerve damage then the pill is the way to go!

You can go to our website for more information: www.houghear.org

 

[Justin De Moss]

@Justin De Moss

When you said they will fund half the cost is that to include tinnitus as an indication?

Also is the $750k what you need to raise, or do you need to raise $375k?

It's looking like we probably have raised $300K for the tinnitus proof of concept study. Once that is confirmed by Oblato and OCAST then I'll make an announcement. So we are down to $435K, of which I've already started raising funds with. We have a challenge match going on right now as well so I'm confident we'll hit this goal by mid-year.

 

[Justin De Moss]

It's $735k. I don't think Oblato is funding half of that.

They have said they are interested in matching an OCAST grant for $150K for tinnitus. If confirmed, that will be $300K of the $735K needed and we can start the research!

 

[Justin De Moss]

You believe the pill can restore damaged nerve endings and synapses in a cochlea in humans which basically means it could treat cochlear synaptopathy. Did HEI develop a method to diagnose cochlear synaptopathy in alive humans? Are you able using your diagnostic methods to say that certain individual has damaged synapses?

According to my last year discussion with Massachusetts Eye & Ear Infirmary researcher till now there was no reliable method to diagnose cochlear synaptopathy in alive humans, it was possible only post mortem. If you managed to find one it means a big step forward in our understanding of inner ear dysfunctions.

I really don't know how to answer this. I'll have to kick this up to one of the researchers.

 

[Justin De Moss]

I stated nothing as fact. I used the word presumably. If I'm wrong about Oblato then so be it. That does not change Oblato, the new partner, requiring a proof of concept for it to study the pill against tinnitus.

"The reason we need to raise more money for a proof-of-concept study is to show 1) tinnitus can be tested objectively, demonstrate the cost of doing so, show that it can be successful, and illuminate the target demographic of those who suffer from tinnitus."

To show tinnitus can be tested objectively means you need bio-markers. Something to physically identify tinnitus. Nobody has that. That's the single hardest part in tackling this condition. You get that and it's simply a matter of time until this is cracked. You get a true biomarker and you will have your golden ticket. Yes, word scores for speech in noise and general hearing tests, but not all who have tinnitus have hearing loss. The target demographic is already illuminated.

As far as I'm concerned you're still at square one, and this partner is a side avenue.

Like I say, if you get FDA approval for the cochlear implant trauma, you will very quickly have the tinnitus community buying this pill and letting you know if it works or not.

Bottom line, I was rooting for Hough Ear Institute in a big way. But setback after setback and then some kind of false excitement really sours it.

I don't mean to be a jerk about it. I respect you for fighting the good fight. But I'm pissed. I'm suffering and I'm fresh out of patience.

Well, I'll keep fighting brother. I'm going to get this proof of concept study funded. We are going to do all we can to help you and others.

 

[Justin De Moss]

Off topic a little, but how can one tell if the auditory nerve has been damaged? An ENT said mine probably was and that the hair cells probably hadn't been affected. No idea how she 'knows' this though.

Usually one of the first signs that nerve damage has occurred is difficulty understanding speech, not hearing it. Hidden hearing loss is another example. There are other reasons - but that is why they are the doctor !

 

[Justin De Moss]

That's my understanding that auditory nerve endings and synapses should be repaired, but better to ask @Justin De Moss.

Yes, the auditory nerve. The pill helps regenerate meaningful nerve connections between the cochlea and the auditory nerve.

 

[Momme]

Usually one of the first signs that nerve damage has occurred is difficulty understanding speech, not hearing it. Hidden hearing loss is another example. There are other reasons - but that is why they are the doctor !

If I have trouble sometime understanding what someone is saying, is it possible nerve damage in my case and not hair cell damage? My audiogram is normal with slight hearing loss (16 dB).

 

[Mentos]

I really don't know how to answer this. I'll have to kick this up to one of the researchers.

I mean how do you know nerve endings are restored, there have to be some diagnostic tool in place, right?

 

[IAmCalifornia]

@Justin De Moss

Just wanted to say thanks for all you're doing. You don't need to engage with us, but you do, and that's extremely appreciated.

 

[all to gain]

Usually one of the first signs that nerve damage has occurred is difficulty understanding speech, not hearing it. Hidden hearing loss is another example. There are other reasons - but that is why they are the doctor !

So you mean a person can hear the speech but not understand it? My understanding of speech is difficult to assess as I spend much of my time speaking to a 3-year old in English and the rest of time speaking a foreign language to adults and flipping between one and the other, which means I have to be switched on anyway to understand everything and to not miss anything.

I tried the hidden hearing test on your site and got 11/14. I couldn't understand the last two or the fourth one from last. Don't know how accurate the test is or what my score means.

Having read about auditory nerve damage, I don't have vertigo or dizziness, so presumably the vestibular nerve isn't damaged. And having had an MRI, it showed that I don't have an acoustic neuroma.

My audiogram showed mild hearing loss with dips at 4000 Hz in one ear and 6000 Hz in the other and then a sharp drop off at 8000 Hz. I am 50.

 

[Niatoolit]

Can somebody give me a clear answer on when this is going to be available? Is it mid 2020? Or mid decade of 2020s?