Retigabine (Trobalt, Potiga) — Petition to the ATA

[attheedgeofscience]

You presented this to the ATA already?

No. It's for "other purposes".

 

[valeri]

@attheedgeofscience for the president

 

[attheedgeofscience]

Update regarding study on Trobalt.

A small group of TT-members has been reaching out to various individuals and organizations within the tinnitus research community and specific parts of the DoD. The reality of life is that it is not always certain as to how to proceed with a "mission" even when the goal and objective is clear. Finding the right people can - sometimes - be a bit of a "trial and error" process. However, we now seem to have found one potential avenue which definitely warrants further attention. We are in contact with a tinnitus research centre and they have shown a genuine interest in the material we have presented to them. Below is an excerpt from the correspondence of one of the researchers (to us)...

I just spoke with <name withheld by ATEOS> and I just wanted to get back to you to tell you how enthusiastic we are about your work and your motivation.

First, thank you for the detailed information. We will go through it in detail and then try to develop a case report form with specific questions covering additional information of interest.

I do not wish to disclose the name of the research centre - at least not at this moment - but it seems quite likely that there are grounds for continued collaboration.

Of specific interest, I should mention that the researcher(s) are so far not concerned about the wide spread of variability in the improvement results among participants in the informal trial. Instead, they see it as testimony to the many "sub-types" of tinnitus etiologies (and hence why some participants experience a better improvement than others). What is important is that at least some participants experience(d) relief from the medication (ie. "it works"). The researchers have also asked for details on side-effects; this has been provided. For now, we await further progress once the tinnitus centre has had a chance to digest the data.

At this point, I would like to thank the so-far-undisclosed TT-team behind this initiative. I would also like to thank the group of researchers who have assisted us with the pharmacological mechanism-of-action of Trobalt in relation to tinnitus suppression; it is unfortunately not possible to thank them publicly as I do not wish to disclose their names. In addition, I would like to thank the group of professors behind the pioneering research paper titled "Pharmacodynamics of potassium channel openers in cultured neuronal networks", released online March 25, 2014. Lastly, I would like to thank @Dr. Nagler for having been willing to draft the ATA petition for us.

attheedgeofscience
17/DEC/2014.

 

[Dr. Nagler]

Lastly, I would like to thank @Dr. Nagler for having been willing to draft the ATA petition for us.

If the investigator with whom you are communicating is well-regarded and decides to do the study, by bypassing ATA you have saved yourself a year ... maybe more. Well done.

Dr. Stephen Nagler

 

[valeri]

@attheedgeofscience

Is the research centre you're communicating with aware of Autifony and what they are trying to achieve?
The reason for this question is if they see it as a similar if not the same thing and would that make them stir away from any further studies on RTG.

 

[attheedgeofscience]

Is the research centre you're communicating with aware of Autifony and what they are trying to achieve?

The simple, short, and correct answer (at this stage) is: I don't know. Because I don't (we have not discussed this topic).

The reason for this question is if they see it as a similar if not the same thing and would that make them stir away from any further studies on RTG.

The purpose of doing a study of Trobalt in relation to tinnitus suppression is separate from a clinical trial such as AUT-63. Trobalt is an existing product on the market; AUT-63 is not.

There is no particular reason why a study of Trobalt - independently of AUT-63 - should not go ahead provided it demonstrates enough basic anecdotal ability to combat tinnitus. Why is that? Well, we don't know if AUT-63 will ever make it to the market. What if we assume - incorrectly - that AUT-63 will become a success and... it turns out not to be? Then what? Then we would have wasted - who knows - 5 or 6 more years only to find out that we don't have a pharmacological alternative available to us. I agree that there is some overlap between the two. But you cannot make decisions based on what you don't know. The goal right now is to achieve something fast. All the researchers I have been in contact with have indicated that they are not too pleased with the known side-effects of Trobalt - which is why you will also have noticed my specific comment in this post...

https://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-petition-to-the-ata.6896/page-5#post-81060

...about the experts' opinion as to whether Trobalt could be end up being curative within a 3-month timeframe (in order to avoid long-term side-effects). As expected, the professors behind the statement were unwilling to offer an opinion because they do not know the answer to such questions according to the high standards of academia that they are operate by. This forum has plenty of arm-chair critics who are willing to propose any theory they please; the professors do not have the same degrees-of-freedom.

 

[valeri]

@attheedgeofscience

Thank you!
I guess I have more questions but probably should leave it for now.

 

[Larry OT]

My neurologist told me that retigabine is losing market share because of the side effects and we should proposition the manufacture to pursue a better tinnitus function and market.

Is the maker of Retigabine aware of the TT trials?

 

[Telis]

Is aut00063 not a more targeted variation of retigabine? Are the scientists working with autifony not originally from Glaxosmithkline (the creator of retigabine)?

I would think that if aut00063 is a no go after the trails, this would rule out retigabine as a tinnitus treatment. On the other hand if aut00063 it is put to market, retigabine would be an inferior choice.

Won't we know this all within a year with aut00063? I don't know, seems as though this ship may have already sailed.

If aut00063 is found to be THE drug for tinnitus within 12-18 months, this information can then be presented as a case for retigabine rather than pursuing additional testing, in my mind this would be a shorter less expensive and a more convincing route to take. If aut00o63 is found to be a dud, then I think it is safe to say that pursuing retigabine is a waste of time and $$$. It's not like this info is years away, by the time all this money and effort is put forward and the testing is underway with retigabine you will have all the answers you need from autifony's results anyway, this without the potential of wasting resources in the process.

Not trying to be negative or kill the vibe here...just my opinion.

 

[AntonR]

@Telis I think its fair to say at this point retigabine is not a dud, its pretty clear that it has very positive effects even at fairly low doses (not in all cases obviously). At this point we've had a fair number of people test it, with mostly positive experiences, sure there can beside effects but for the most part they don't seem THAT serious. All drugs come with a risk.

Even if Aut00063 somehow turns out to be a dud, obviously something in retigabine is working.

 

[Telis]

@Telis I think its fair to say at this point retigabine is not a dud, its pretty clear that it has very positive effects even at fairly low doses (not in all cases obviously). At this point we've had a fair number of people test it, with mostly positive experiences, sure there can beside effects but for the most part they don't seem THAT serious. All drugs come with a risk.

Even if Aut00063 somehow turns out to be a dud, obviously something in retigabine is working.

Well if retigabine works then it shoukd be safe to say autifony will work. And in that case a strong pitch can be made for retigabine in 12-18 month (whenever the results are in) without running through the process of further testing on retigabine.

That's my point, either way the process is kind of in place.

Anyway...just my opinion...I could be way off, there are much more educated individuals than I regarding this subject.

Good luck

 

[Hudson]

Well if retigabine works then it shoukd be safe to say autifony will work. And in that case a strong pitch can be made for retigabine in 12-18 month (whenever the results are in) without running through the process of further testing on retigabine.

That's my point, either way the process is kind of in place.

Anyway...just my opinion...I could be way off, there are much more educated individuals than I regarding this subject.

Good luck

I don't think it's "safe to say" that AUT00063 will work if Retigabine does. Just because it's in the same class of drugs does not mean it's identical in any way. There are a whole host of factors that go into making a medication successful. I think it's promising, but ATEOS has a very good point that retigabine is already on the market and seems to be a decent candidate for treating tinnitus from our own experience here. AUT0063 is not on the market yet and it is by no means a guarantee. He had a very good point that if we just "sit and wait" for AUT0063 to turn out, which it may not, we could potentially lose several years of research that could be going into why retigabine appears to have some success. That research may serve to supplement why AUT00063 works if it turns out to, but further investigation of an already approved drug will only enhance our understanding of potassium channel modulators as a class of drugs (which there are TONS).

 

[attheedgeofscience]

I was not planning on responding to questions concerning pharmacology and efficacy in this thread (or in general) as this is a thread which concerns a study of Trobalt (and not which type of medication will end up more effective and so on). And in any event, it would not be prudent for me to comment on such topics as I do not have a background in medicine or the natural sciences.

However, as is often the case with Internet forums, opinions seem to flourish rather easily. But the following is not an opinion, but a fact...

Earlier on in this thread, I mentioned a new development from a researcher that I had contacted - a development which still remains unpublished:

Dear Jakob,
Thank you for your interest in my research. There is one tinnitus update that I would like to share with you: we have developed and tested a novel and more specific Kv7.2/3 (KCNQ2/3) activator that works much better than retigabine both for epilepsy and for tinnitus. This novel Kv7.2/3 activator is more specific than retigabine and is less toxic, but keep in mind that all this work has been performed only in mice and rats. The manuscript describing this work in detail will be submitted for publication within the next month or so and I hope that the new compound will hopefully go to clinical trials soon.
I am not an MD and therefore clinical trials, effects of drugs on tinnitus sufferers, medical advice, and clinical applications of my findings in humans are outside of my expertise/control. I know the exact MOA of retigabine on Kv7 channels (you can read it in my 20xx publication in <name withheld>), but I do not know the MOA of retigabine on tinnitus and therefore I can not answer your question.

Within the undisclosed TinnitusTalk-group pursuing the efforts for a study of Trobalt, there has been further communication with the researcher in question. Based on that, I can confirm the researcher's expert opinion that the "modified" version of Trobalt, mentioned above, will in his/her belief be superior to AUT-63. Of course, the work so far relies purely on animal studies, but that was the researcher's estimate at this stage.

Trobalt targets the full Kv7.2-5 range, whereas the above development is specific to Kv7.2/3; it is less toxic and more specific in relation to tinnitus (and epilepsy).

While the above development may have an element of uncertainty associated with it, the following is pretty clear:

1) Trobalt is a drug available on the market at-the-moment.
2) A study can be conducted on the drug - Trobalt - proving (or disproving) its efficacy in relation to tinnitus, in general, or in relation to specific sub-types of tinnitus that initial results of our informal trial may be pointing to.
3) The above can take place regardless of any other development that may - or may not - be occuring within the field of tinnitus research.
4) There is a need for a pharmacological treatment (now).

I can only encourage members of this forum to engage in debate based on facts and well-reasoned opinions rather than speculation.

attheedgeofscience
18/DEC/2014.

 

[tomm]

Will the paper be published for us to read next month? Has it got a title we can look for or will they let you know?

 

[dan]

Based on that, I can confirm the researcher's expert opinion that the "modified" version of Trobalt, mentioned above, will in his/her belief be superior to AUT-63. Of course, the work so far relies purely on animal studies, but that was the researcher's estimate at this stage.

This statement has intrigued me. How would he know if his drug would be superior to AUT-63 ? He is admitting he has no knowledge as to the MOA of RTG (and I suppose for his modded RTG) for tinnitus.
In animal models AUT-63 showed near 100% efficacy.
Can you elaborate on why he thinks his drug would be superior?

 

[Steve]

Something very interesting was pointed out to us today.

The people who did not get any benefit, or showed only minimal benefit, listed the cause of tinnitus as acoustic trauma (apart from 2 with no known reason).

 

[attheedgeofscience]

Can you elaborate on why he thinks his drug would be superior?

Not really @dan, because that would be speculation rather than a fact (and I prefer to deal in facts, as you know). An expert is entitled to his or her opinion/belief - and that is what he/she provided (as stated).

The point is that certain people in various threads on this board are making all kinds of conclusions/assumptions - the AUT-63 thread is "full of them" (eg. efficacy-, non-disclosure-, trial start date- assumptions, etc). All it takes is to pick up the phone/write an e-mail.

As promised, I will track down more info about any initial AUT-63 phase-II trial results I can get my hands on (from my earlier source this Summer).

Regarding the Trobalt study, I can only say that - today - has been another success (at least indirectly). The total combined PMs exchanged at this point is... well... I don't know exactly, but it is more than 200...! Two workgroups were initially created (one for the MoA and another for funding; the two groups have now been merged into one as we have a more clear "way forward" as well as "volunteers with a mission"). The group is small but the right direction/contacts seem to be moving into place.

That's all I have to say.

 

[attheedgeofscience]

He is admitting he has no knowledge as to the MOA of RTG

No one has knowledge of the exact MoA of Trobalt (in relation to tinnitus). No one...

 

[dan]

Two workgroups were initially created (one for the MoA and another for funding; the two groups have now been merged into one as we have a more clear "way forward" as well as "volunteers with a mission"). The group is small but the right direction/contacts seem to be moving into place.

Wow that is really amazing, what you have done is outstanding.

 

[jeannie]

I agree with Dan. attheedgeofscience,, thank you for all you have done!!

 

[Telis]

I don't think it's "safe to say" that AUT00063 will work if Retigabine does. Just because it's in the same class of drugs does not mean it's identical in any way. There are a whole host of factors that go into making a medication successful. I think it's promising, but ATEOS has a very good point that retigabine is already on the market and seems to be a decent candidate for treating tinnitus from our own experience here. AUT0063 is not on the market yet and it is by no means a guarantee. He had a very good point that if we just "sit and wait" for AUT0063 to turn out, which it may not, we could potentially lose several years of research that could be going into why retigabine appears to have some success. That research may serve to supplement why AUT00063 works if it turns out to, but further investigation of an already approved drug will only enhance our understanding of potassium channel modulators as a class of drugs (which there are TONS).

Well...the way I see it, this class of drug is already currently being explored for the treatment of tinnitus through autifony.

And yes there are "TONS" so why this one? As far as retigabine being a viable option to treat tinnitus in the mean time, I think not. What is the plan, you take it until it makes you sick in 6 months? There is a reason this drug is banned and deemed unsafe in a lot of countries.

 

[dan]

Well...the way I see it, this class of drug is already currently being explored for the treatment of tinnitus through autifony.

And yes there are "TONS" so why this one? As far as retigabine being a viable option to treat tinnitus in the mean time, I think not. What is the plan, you take it until it makes you sick in 6 months?

I agree, RTG isn't a viable option to treat tinnitus, but the reason people are trying it is because there is a very small chance for remission, as in Mpt's case.
My intuition tells me that AUT-63 will be at least as good as RTG, after all it did awesome in pre-clinical tinnitus experiments.
However RTG clearly does not work for everyone and it also seems to lose its efficacy over time. I hope AUT does better.

 

[amandine]

@Telis

I know that you are feeling bad and are suffering.
My heart goes out to you.
We are all suffering in different ways and some of that suffering is not just to do with T but may deeply affect or worsen it. We all bleed and feel pain.
However your comment re the trobalt is hardly fair.
How do you know that people will have to take it for six months and eventually get sick?
You dont know that. None of us know it can be taken for a while and result will reduce the T or kill it and /or stop without it returning.
Maybe you are right or maybe wrong. People are trying for themselves to kill their T. Yes they are taking great risks but it is personal choice.
Like in the early days of HIV and Aids when sufferers took all and anything in the hope of extending their life and avoiding sickness, so are people here on TT taking trobalt for the same reasons.
Give everyone a chance - this is the only way that any progress will be made.
For sufferers of T there is little help. Those who had HIV at least had the backing of the medical world to try to find some therapy as quickly as possible to stem the epidemic from spreading worldwide.
For those with T, medical field isnt so concerned by how many have this terrible affliction.
So there is little choice but to experiment even if those drugs are dangerous.
I am sure Telis that, if this drug proves to be workable and a daily dosage for a limited time is established which will then greatly improve the level of T or indeed eradicate it, you will avail your self of this drug to be healed alongside the rest of us.
Let us be grateful for all those willing to risk what health they have to take this drug.
Thanks and with wishes that your nights will be sweet and your days fulfilling.

 

[Larry OT]

He is admitting he has no knowledge as to the MOA of RTG
No one has knowledge of the exact MoA of Trobalt (in relation to tinnitus). No one...

The exact MOA of most drugs, if not all that involve the brain is unknown.
I record MOA's for a pharma ad agency. Just about all of them use the expression
"The exact MOA is not known". They all hypothesize how the drug works.

 

[Telis]

@Telis

I know that you are feeling bad and are suffering.
My heart goes out to you.
We are all suffering in different ways and some of that suffering is not just to do with T but may deeply affect or worsen it. We all bleed and feel pain.
However your comment re the trobalt is hardly fair.
How do you know that people will have to take it for six months and eventually get sick?
You dont know that. None of us know it can be taken for a while and result will reduce the T or kill it and /or stop without it returning.
Maybe you are right or maybe wrong. People are trying for themselves to kill their T. Yes they are taking great risks but it is personal choice.
Like in the early days of HIV and Aids when sufferers took all and anything in the hope of extending their life and avoiding sickness, so are people here on TT taking trobalt for the same reasons.
Give everyone a chance - this is the only way that any progress will be made.
For sufferers of T there is little help. Those who had HIV at least had the backing of the medical world to try to find some therapy as quickly as possible to stem the epidemic from spreading worldwide.
For those with T, medical field isnt so concerned by how many have this terrible affliction.
So there is little choice but to experiment even if those drugs are dangerous.
I am sure Telis that, if this drug proves to be workable and a daily dosage for a limited time is established which will then greatly improve the level of T or indeed eradicate it, you will avail your self of this drug to be healed alongside the rest of us.
Let us be grateful for all those willing to risk what health they have to take this drug.
Thanks and with wishes that your nights will be sweet and your days fulfilling.

Me feeling bad or suffering has nothing to do with my opinions. I am just adding what I feel to be very valid points. If people disagree that's great, this is just a discussion, no big deal.

 

[attheedgeofscience]

However RTG clearly does not work for everyone and it also seems to lose its efficacy over time. I hope AUT does better.

The 2nd part of the sentence below may be important. Whether it will end up being important is another matter - but at least, that is why studies (should) exist...

2) A study can be conducted on the drug - Trobalt - proving (or disproving) its efficacy in relation to tinnitus, in general, or in relation to specific sub-types of tinnitus that initial results of our informal trial may be pointing to.

 

[lapidus]

Something very interesting was pointed out to us today.

The people who did not get any benefit, or showed only minimal benefit, listed the cause of tinnitus as acoustic trauma (apart from 2 with no known reason).

But our beloved patient zero Mpt got his from ear syringing i.e acoustic trauma.

 

[attheedgeofscience]

But our beloved patient zero Mpt got his from ear syringing i.e acoustic trauma.

I know what you mean, but I would be careful with these types of assumptions.

Acoustic trauma may be clinically different from trauma to the ear (eg. ear syringing) - at least from a tinnitus perspective.

 

[Steve]

But our beloved patient zero Mpt got his from ear syringing i.e acoustic trauma.

I would say that acoustic trauma is damage to the ear caused by noise, so it is a different category.

 

[Markku]

But our beloved patient zero Mpt got his from ear syringing i.e acoustic trauma.

I got my tinnitus from syringing and I don't consider it acoustic trauma.

It wasn't loud enough to be considered as such.