Hough Ear Institute's Hair Cell Regeneration Project

[Justin De Moss]

Yes, Justin emailed me that last night. Great news! Do you know how long this proof of concept study will take before we have something more concrete to hope for?

Hi Deb! The PoC study takes a total of 12 months.

 

[Justin De Moss]

I sure don't. But it's my hope that this trial will serve our community really well, because Frequency Therapeutics is only testing for hearing regrowth and not really focusing on tinnitus like this trial will do. I'm hoping we have direct information on how people's tinnitus reacts to this drug.

It's complicated. Frequency Therapeutics is doing good work. There are more than likely multiple causes of tinnitus. Their approach might be helpful. Our approach might be helpful.

Our hope is to have a phase 2 study, not a phase 2a, with the primary objective in treating tinnitus. We will have results in 12 months.

 

[Justin De Moss]

Frequency Therapeutics is also testing the effect of their drug on tinnitus, but their main focus is hearing regrowth.

Yes, it is the secondary objective in a phase 2a study. Not a full phase 2 study. It involved less than 100 subjects. A phase 2 study involves hundreds of subjects.

 

[Justin De Moss]

You can do an advance search on ClinicalTrials.gov and search by Sponsor with Hough or Oblato or Auditus (the latter two are partners with Hough). So far, I have found no clinical trials regarding hearing loss or tinnitus by any of them.

It would be really nice if Hough could post an update on their Hough Ear Institute website if they're starting clinical trials on their advertised "Pill", and especially including a direct link to ClinicalTrials.gov.

The process of a Phase II study and the actual phase 2 study are different, somewhat. The process begins with the study design, funding, securing the research company, etc. Then once all the information is ready to go, it is announced via clinicaltrials.gov.

So, the process has started even though the actual phase 2 study is yet to be announced.

 

[Mentos]

First off, if I said "we are starting phase 2 studies" that was a miscommunication. Hough Ear Institute doesn't run the trials. The biotech company, Oblato, who has exclusive license to the drugs will be running them. The process has started for a phase 2 study. There is a lot to the process.

It's best not to read into what is said. Context is important. Because the process is started, doesn't mean that we are already at a point of selecting candidates for the trials Sometimes I say we have started and "we" have, as in Oblato. Sometimes I say they haven't started because of the context - people are wanting to sign up. That part has not started.

Does that make sense?

Do I read it correctly that Oblato will initiate the phase 2 already this year, not for tinnitus but for hearing restoration only?

And the clinical trial for tinnitus could only start once the proof of concept has been finalized?

If so, there would be room for off-label use for tinnitus even if tinnitus was not indicated in the clinical trial measures.

 

[AnxiouslyWaiting]

The PoC study is to test an objective measurement of tinnitus as well as to see if it works for chronic tinnitus. All of our previous studies indicated that it does, but for chronic tinnitus, the sample size was a little on the small side. Yet, we did have statistical significance.

The biotech company agrees with us, hence the reason they are funding nearly half the study to find out if it is worth the millions to run a phase 2 study. If successful - this will be the first phase 2 study that has as it's PRIMARY objective the treatment of tinnitus. It will also be the first, to my knowledge, of objectively measuring tinnitus.

Thanks for the information @Justin De Moss.

Were these studies done on human or animal subjects?

I'm just curious if we have any human anecdotes on tinnitus and the Hough Pill. If not, hopefully we will have soon.

 

[urgentresearch]

First off, Hough Ear Institute doesn't run the study. I'm not sure why people keep thinking that we do but we don't. The biotech company does. They will choose whatever indication they want to study. They can choose one, two, three, etc.

To be clear - Phase 1 is complete. Phase II is funded and ready to start once they determine which indication(s) they want to do. Additionally - we are doing a proof of concept study because the biotech company has a desire to do a tinnitus phase 2 study as its primary objective.

Thank you for the additional context, @Justin De Moss.

 

[FGG]

@Justin De Moss, just to clarify, when you said:

"One difference between Frequency Therapeutics and Hough Ear Institute is that we hope to run a phase 2 study that has tinnitus as the primary goal/finding, not secondary. The second is objectively measuring results v. a self-report style which is extremely unreliable depending on sample size."

You mean to contrast your proof of concept study from Frequency Therapeutics' study because you will be using things like gap detection to objectively measure tinnitus in rodents and not that Hough Ear Institute have developed an objective measure for tinnitus that can be used in humans, right? You won't be using an objective measure in your phase 2 study on humans or will you? Because that would be huge news if so!

 

[weab00]

I messaged the Hough Ear Institute on Facebook asking for an approximate timeline and they said 2026-2027. 6-7 years is such a long time to continue suffering, hopefully drugs like Pipeline Therapeutics or Otonomy will be out much sooner...

 

[tommyd87]

I messaged the Hough Ear Institute on Facebook asking for an approximate timeline and they said 2026-2027. 6-7 years is such a long time to continue suffering, hopefully drugs like Pipeline Therapeutics or Otonomy will be out much sooner...

It has gone from 2024/25 to 2025/26 to 2026/27. Something seems questionable. It could be that different people have been saying different things on behalf of Hough Ear Institute which is just an unfortunate situation. It could be that there have been further delays which have not been clearly communicated.

 

[paul mclean]

@all to gain sup man, I found the patent for the Hough Ear Institute pill.

It is 300mg/kg of NAC and NXY-059 (Disufenton sodium).

Give the patent a read. It tells you everything you want to know. I will give this a go I reckon.

https://www.freepatentsonline.com/y2018/0117115.html

 

[FGG]

I messaged the Hough Ear Institute on Facebook asking for an approximate timeline and they said 2026-2027. 6-7 years is such a long time to continue suffering, hopefully drugs like Pipeline Therapeutics or Otonomy will be out much sooner...

I think it's very likely they will.

Hough Ear Institute chose cochlear implant patients as their study population which means the study can't be carried out at routine ENT centers (like Pipeline Therapeutics and Otonomy) and would be way more subject to delays from COVID-19 etc.

 

[tommyd87]

Firstly, @Justin De Moss, I would like to apologise if any negative experiences were had as a result of the previous posts. It was not my intention to attack you personally but rather simply discuss the matters relating to Hough Ear Institute's Pill treatment.

I think that part of the confusion around my incorrect claim that a drug could not be used off-label had stemmed from reading dodgy information and/or misinterpreting facts.

I had read papers which seemingly indicated that off-label use also included early access use. I later found out that this is wrong and not what the definition of off-label use according to the FDA guidelines is.

There is more data for hearing loss (cochlear implant trauma, NIHL, ototoxicity) than for tinnitus. It has nothing to do with confidence. The PoC study costs $735K. Oblato is paying for $300K of it, the state of Oklahoma is paying for $300K of it. That leaves $135K for us to raise for it. I'd say a lot of scientists are pretty confident in the work.

Your burning question is actually a false assumption - they are paying, for nearly half of it!

I wouldn't disagree with you that a lot of scientists are confident in the work.

What I would disagree with however is whether the "burning question" is a false assumption.

The questions around Oblato's confidence in the Hough Ear Institute's Pill treating tinnitus have been raised multiple times on multiple different platforms and by multiple different people.

I think that rightly or wrongly, the reason people questioned Oblato's confidence in the treatment is because they believed that the information disseminated by Hough Ear Institute to explain the reasons for needing to complete a proof of concept study for tinnitus and the reasons Hough Ear Institute needs to fund part of this study themselves have been confusing, lacking and also even contradictory at times. This has ultimately meant that they have felt that they have not got clear answers to these questions.

I think that these concerns about Oblato's lack of confidence in the treatment have been further supported and fuelled by the fact that there have been situations where people have misinterpreted what Hough Ear Institute has said. Also there have been examples of Hough Ear Institute needing to correct and clarify what they have said as well.

While I don't disagree that the more recently posted information indicates that the scientists are confident in the treatment and that the science supports this Pill delivering positive outcomes, this still doesn't seem to completely answer the two key questions of

- First, why does Hough Ear Institute need to fund part of the Proof of Concept study?
Since Oblato appear to be the sole financial beneficiary from the sale of the Pill and since scientists seem confident that the treatment stacks up, one can logically deduce that this should lead to Oblato being willing to cover the remaining costs of the proof of concept study. This is because Oblato will be the company who stands to financially benefit from the sales of this apparently successful treatment and should be able to recoup the costs of this study from sales.

and

- Second, why does a proof of concept study for tinnitus need to be completed when there is already more data and positive data to indicate that the treatment might pass trials for designations other than tinnitus?
Wouldn't it just be simpler and also possibly faster to have this medicine approved for one of the other designations and then simply just allow it to be used off-label for tinnitus?

I would also note, looking at the process from a business perspective, alarm bells ring and concerns are raised when I see something which on the face of it has an excellent business case and appears to be a solid product which is well supported by evidence, but yet does not have its development fully funded by the company who is ultimately going to be selling it. This is even more of an issue when there is a lack of direct and detailed information explaining why this is the case.

In relation to Hough Ear Insitute's Pill, this tells me one of three things:

- 1) A company other than Oblato is going to be benefiting financially from the sale of the Hough Ear Institute's Pill and this has not been clearly disclosed at this time.
For example, this could be Hough Ear Institute themselves or it could be the medical company that Dr. Kopke is currently the chair of.

Thus it could be interpreted that the reason Hough Ear Institute needs to fund outstanding costs associated with the development of the treatment (like this tinnitus proof of concept study) is because Hough Ear Institute is currently the undisclosed second company that will benefit from the sale of the treatment. Thus by contributing to the development, it enables Hough Ear Institute to retain part ownership of the treatment and therefore gain revenue from its sale.

- 2) Oblato has concerns about the effectiveness of the Hough Ear Institute's Pill for the treatment of tinnitus and as a result requires proof that this is effective.
There has been some further evidence given to alleviate concerns around the effectiveness of the treatment. However, the glaring issue still is why hasn't Oblato funded the outstanding balance for the proof of concept study for tinnitus if they are the ones who will financially benefit from its sale.

- 3) There is some unexplained reason or reasons why Hough Ear Institute's Pill needs to go through multiple trial designations for FDA approval (which includes tinnitus trials).
This is opposed to going through only one designation such as ototoxic medication treatment and then being used off-label for other possible uses such as tinnitus. There has been some further explanation as to why there needs to be a further phase 2 trial for tinnitus, however there is still no clarity as to why it must go down the full proof of concept study route, followed by the trial route for multiple designations.

I believe that all three of these concerns have also been raised at various points by multiple people when discussing the Hough Ear Institute's Pill. Thus I strongly believe that also addressing these issues will alleviate many concerns that people have had with the information provided in relation to the various aspects of the treatment.

FDA approval often leads to a fast track with other country's equivalent to the FDA.

Also, it fits in our mission. We can purchase the drugs and through our humanitarian efforts - deliver it to those in most need. Our founder and doctors have been to over 80 countries offering their services and medicine for free. But we have to have FDA approval first.

Yes, I am well aware that the medicine trials completed in one country usually lead to the medicine being approved in some other countries. I know that this happens with Australia and America and vice versa for example.

I think it's very likely they will.

Hough Ear Institute chose cochlear implant patients as their study population which means the study can't be carried out at routine ENT centers (like Pipeline Therapeutics and Otonomy) and would be way more subject to delays from COVID-19 etc.

I will let Justin De Moss answer this, although from what I have seen and what has been posted, it appears that the Pill trials are potentially getting done for multiple designations and not just the cochlear implant designation.

It also seems that based off of the information that has been previously posted about the clinical trial process that the pill might be taken through one designation or five designations depending upon what Oblato decides.

It should also be noted that I don't think that Hough Ear Institute is taking the pill through the trials at all and that Hough Ear Institute is not deciding what designations it should be trialled for either. Rather that decision is left to Oblato.

 

[Piney]

I found the patent for the Hough Ear Institute pill.

It is 300mg/kg of NAC and NXY-059 (Disufenton sodium).

I have a bottle of 600 mg NAC in my cabinet.

What's the other drug? A salt? I don't get it. Am I missing something? Aren't there other ingredients in the Hough Ear Institute Pill?

 

[all to gain]

I have a bottle of 600 mg NAC in my cabinet.

What's the other drug? A salt? I don't get it. Am I missing something? Aren't there other ingredients in the Hough Ear Institute Pill?

Yeah, you may have a 600 mg bottle, but 300mg/kg would mean 24,000mg for an 80 kg man (176 lbs). You'd soon be getting through that bottle... not that it would matter

 

[all to gain]

@all to gain sup man, I found the patent for the Hough Ear Institute pill.

It is 300mg/kg of NAC and NXY-059 (Disufenton sodium).

Give the patent a read. It tells you everything you want to know. I will give this a go I reckon.

https://www.freepatentsonline.com/y2018/0117115.html

As far as I can remember the non-NAC ingredient is only sold to pharma companies and is VERY expensive.

Please someone tell me if I have my facts on that right as I don't want to be giving false information.

 

[FGG]

As far as I can remember the non-NAC ingredient is only sold to pharma companies and is VERY expensive.

Please someone tell me if I have my facts on that right as I don't want to be giving false information.

Mostly right. It's sold to research facilities (e.g. at universities) as well which was an "in" members were trying to use to get it.

 

[ajc]

As far as I can remember the non-NAC ingredient is only sold to pharma companies and is VERY expensive.

Please someone tell me if I have my facts on that right as I don't want to be giving false information.

Mostly right. It's sold to research facilities (e.g. at universities) as well which was an "in" members were trying to use to get it.

It's only $1070 for 200 mg.

https://www.selleckchem.com/products/NXY-059.html

 

[GBB]

Quick question from a lay person - isn't the amount of NAC needed for a dose enough to induce liver failure (300mg / kg)? I'm probably an idiot but what am I missing?

 

[sssing]

@all to gain sup man, I found the patent for the Hough Ear Institute pill.

It is 300mg/kg of NAC and NXY-059 (Disufenton sodium).

Give the patent a read. It tells you everything you want to know. I will give this a go I reckon.

https://www.freepatentsonline.com/y2018/0117115.html

That's a lot of NAC to take! I'm not sure about liver failure since NAC is used to prevent liver failure with aspirin overdose.

 

[xyz]

Quick question from a lay person - isn't the amount of NAC needed for a dose enough to induce liver failure (300mg / kg)? I'm probably an idiot but what am I missing?

Yes, there is a case report in the NAC thread where a young girl died from NAC overdose. But I am not sure if 24 g in one shot is already in the toxic range.

 

[paul mclean]

Interesting part of the patent.

"Our results show HPN-7/NAC can restore hearing dysfunction caused by noise, and ABR wave amplitudes can be used to monitor synapse loss and treatment effects with medicine.

In summary, our results shows that HPN-07 represents a safe pharmacological means to regenerate lost ribbon synapses in the inner ear, providing a promising non-invasive alternative for treating cochlear synaptopathy and its associated prevalent clinical manifestations, such as difficulty understanding speech in noisy environments, presbycusis, hyperacusis and tinnitus."

 

[GBB]

Yes, there is a case report in the NAC thread where a young girl died from NAC overdose. But I am not sure if 24 g in one shot is already in the toxic range.

I mean a normal daily dose is like 1200 mg.

Interesting part of the patent.

"Our results show HPN-7/NAC can restore hearing dysfunction caused by noise, and ABR wave amplitudes can be used to monitor synapse loss and treatment effects with medicine.

In summary, our results shows that HPN-07 represents a safe pharmacological means to regenerate lost ribbon synapses in the inner ear, providing a promising non-invasive alternative for treating cochlear synaptopathy and its associated prevalent clinical manifestations, such as difficulty understanding speech in noisy environments, presbycusis, hyperacusis and tinnitus."

Let's storm the factory so we can go on with our lives.

 

[paul mclean]

@GBB, that's 2 patents I've read on cochlear synaptopathy that have said it is the cause of tinnitus and repairing synapses heals tinnitus.

I contacted a biotech company about the price of NXY-059 and it is quite expensive. 500 grams is $22,000 USD.

You can get NAC really cheap from wholesalers online. Wonder what the lowest dose is where there is therapeutic benefit?

"To promote or enhance synaptogenesis and neuritogenesis, 2,4-DSPBN can be administered at a dose of, for example, between about 1 mg/kg to about 500 mg/kg body weight, or between about 5 mg/kg to about 400 mg/kg body weight, or between about 10 mg/kg to about 300 mg/kg body weight, or at about 10 mg/kg body weight, or at about 20 mg/kg body weight, or at about 50 mg/kg body weight, or at about 100 mg/kg body weight, or at about 150 mg/kg body weight, or at about 200 mg/kg body weight, or at about 250 mg/kg body weight, or at about 300 mg/kg body weight."

 

[MRItechssuck]

I have been taking NAC at 1800mg for almost a year... no changes. YMMV.

 

[Piney]

Does anyone know what the PoC study consists of?

 

[GBB]

@GBB, that's 2 patents I've read on cochlear synaptopathy that have said it is the cause of tinnitus and repairing synapses heals tinnitus.

I contacted a biotech company about the price of NXY-059 and it is quite expensive. 500 grams is $22,000 USD.

You can get NAC really cheap from wholesalers online. Wonder what the lowest dose is where there is therapeutic benefit?

"To promote or enhance synaptogenesis and neuritogenesis, 2,4-DSPBN can be administered at a dose of, for example, between about 1 mg/kg to about 500 mg/kg body weight, or between about 5 mg/kg to about 400 mg/kg body weight, or between about 10 mg/kg to about 300 mg/kg body weight, or at about 10 mg/kg body weight, or at about 20 mg/kg body weight, or at about 50 mg/kg body weight, or at about 100 mg/kg body weight, or at about 150 mg/kg body weight, or at about 200 mg/kg body weight, or at about 250 mg/kg body weight, or at about 300 mg/kg body weight."

It would be interesting to super dose NAC under the supervision of a doctor, if they would agree to help. Can anyone with a medical background on this forum comment on what the upper range intake *might* be?

 

[FGG]

It would be interesting to super dose NAC under the supervision of a doctor, if they would agree to help. Can anyone with a medical background on this forum comment on what the upper range intake *might* be?

Toxicology studies should be available online... if there are any. I couldn't find any. In fact, this reference says there is no data available except for the LD50 for mice and rats (lethal dose for 50% of sample sizes -- 4400mg/kg for mice and 5050mg/kg for rats):

https://www.caymanchem.com/msdss/20261m.pdf

 

[paul mclean]

@MRItechssuck

Nothing will happen with just NAC. Adding NAC to NPH-07 (2,4-DSPBN) has high synergy together but you need (2,4-DSPBN) most importantly.

 

[tommyd87]

I have been taking NAC at 1800mg for almost a year... no changes. YMMV.

Maybe NAC isn't effective enough solo.