Prof. Thanos Tzounopoulos Receives $2 Million Grant

[Padraigh Griffin]

Email sent to Prof. Thanos again. Hoping for a comment. Can't understand why he won't comment at all on XEN1101, or for all my worth I cannot understand why he wasn't asked about it in the Tinnitus Talk Podcast interview. Maybe he will do another interview soon. His interview was excellent. He really is an expert on the condition.

Here is my email:

Dear Professor,

I have been chasing you for a comment for many months yet you remain silent.

It is a pity as we would love to get your highly qualified opinion on XEN1101.

XEN1101 is a reformulation of Retigibaine by Xenon Pharmaceuticals , which is a publicly listed Biotech that has completed a large PHASE 2 for Epilepsy with its compound, with very favourable results, without the severe side effects of Retigibaine. Indeed the side effects were minimal vs placebo at the suggested dose level of 20mg.

They are hoping to initiate a PHASE 3 in the near future.

Xenon Pharma have also started a Phase 2 for Depression with a reformulation of Retigibaine that has near identical potency and selectivity to your proposed compound.

https://clinicaltrials.gov/ct2/show/NCT05376150

Why you won't comment on this drug is perplexing me?

I hate to be constantly emailing, but us sufferers would value your opinion.
I apologise for my persistence!

Surely the similarity to your work is something of interest to you?

I have CC'd the founder of Tinnitus Talk as your interview with TT a year or so ago made compelling listening.

Kind regards,
Padraigh​

 

[ThomasC]

Email sent to Prof. Thanos again. Hoping for a comment. Can't understand why he won't comment at all on XEN1101, or for all my worth I cannot understand why he wasn't asked about it in the Tinnitus Talk Podcast interview. Maybe he will do another interview soon. His interview was excellent. He really is an expert on the condition.

Here is my email:

Dear Professor,

I have been chasing you for a comment for many months yet you remain silent.

It is a pity as we would love to get your highly qualified opinion on XEN1101.

XEN1101 is a reformulation of Retigibaine by Xenon Pharmaceuticals , which is a publicly listed Biotech that has completed a large PHASE 2 for Epilepsy with its compound, with very favourable results, without the severe side effects of Retigibaine. Indeed the side effects were minimal vs placebo at the suggested dose level of 20mg.

They are hoping to initiate a PHASE 3 in the near future.

Xenon Pharma have also started a Phase 2 for Depression with a reformulation of Retigibaine that has near identical potency and selectivity to your proposed compound.

https://clinicaltrials.gov/ct2/show/NCT05376150

Why you won't comment on this drug is perplexing me?

I hate to be constantly emailing, but us sufferers would value your opinion.
I apologise for my persistence!

Surely the similarity to your work is something of interest to you?

I have CC'd the founder of Tinnitus Talk as your interview with TT a year or so ago made compelling listening.

Kind regards,
Padraigh​

Honestly your email sounds rude. I don't think he is going to reply. You're basically telling him that his research is a waste of time because other drugs are at a more advanced stage.

 

[Padraigh Griffin]

Honestly your email sounds rude. I don't think he is going to reply. You're basically telling him that his research is a waste of time because other drugs are at a more advanced stage.

Yes I understand it sounds a little rude. I was hoping not to come across that way too much.

What I can certainly say is RUDE is:

A funded by public money tinnitus researcher that is working on a reformulation of Retigabine NOT commenting at all on a similar reformulation that has near identical potency and selectivity. He has written papers commenting on all potential tinnitus drugs in development, even off label, BUT has never even acknowledged the existence of a compound that is essentially HIS compound. That is not ethical in my humble opinion. To completely ignore the potential of XEN-1101 is just wrong. He is paid by the government. He is a tinnitus expert and has received Department of Defence funding of over $2M in grants.

He owes it to the public to comment on this XEN-1101 reformulation. Does he not? Surely, he could comment on the reformulation of Retigabine by another company? It is for the good of the people and he is a public servant.

It was about my fifth unanswered email. I could not have been nicer in all of my previous ones. What is also rude, is not answering emails with good valid questions.

Also, he is not a business, but a researcher. If I was asking him to comment on competition then I would agree with you, but he is a researcher and should have a total focus on the progress of Xenon Pharmaceuticals for the GREATER GOOD of tinnitus sufferers. Not just his own personal interests. His research.

Prof. Thanos Tzounopoulos needs to answer these question. Why bother spending taxpayers money if XEN-1101 is essentially the same reformulation? Is XEN-1101 the same compound as his? Or are there differences? What are the differences?

If you don't agree with me, then fine, but I feel very strongly about this and he should be quizzed on XEN-1101 in as much detail as possible from my point of view. Again I remind you he is a public servant, paid by US taxpayers.

He has an obligation to help us all, and if that means holding his hands up and saying yea, XEN-1101 is the same as our compound, then he can spend taxpayers money elsewhere in furthering tinnitus research.

Finally, what have you, I and every other tinnitus suffer to gain from his continued denial of the existence of this potential near term treatment in the form of XEN-1101? The answer is nothing. BUT we could gain from some highly qualified insight into the potential of XEN-1101 that may or may not give us hope.

At least I'm out there chasing these guys.

Prof. Thanos Tzounopoulos has made absolutely no progress towards a clinical trial of any significance in a decade. There is nothing but pardon the pun... SILENCE. And taking a nice pay cheque home at the end of the month.

I admit my approach can sometimes be abrupt, but I'm sick of procrastination and non collaboration and just frustrated that my life is destroyed and the 'researchers' are publishing nice papers and everything but not making solid progress.

Please, Prof. Thanos Tzounopoulos, just tell us if XEN-1101 similar to your compound? That is all. Simple question, and needs a qualified answer. Not moving mountains here.

 

[StoneInFocus]

Finally, what have you, I and every other tinnitus suffer to gain from his continued denial of the existence of this potential near term treatment in the form of XEN-1101? The answer is nothing. BUT we could gain from some highly qualified insight into the potential of XEN-1101 that may or may not give us hope.

I appreciate your effort but what exactly do you hope to gain from the answer?

Both drugs work on exactly the same potassium channels, XEN-1101 has never been tested for tinnitus before, side effects of RL648_81 are unknown, chemical formula of XEN-1101 is a company secret. I'm just curious what extra information you need to know that is so important?

Also, you ask him to "comment" on the drug, but what do you want him to say about it? What information do you want to know that is not available anywhere but from him?

I get that you are frustrated, but I have to agree with @ThomasC here that the email does sound rude. Being impolite definitely won't give you an answer.

I am sure you mean well, but please don't upset one of the few forces working on an actual cure for tinnitus.

Imagine what would happen if we all just start sending him angry emails? Just accept he won't reply to your email.

 

[xyz]

I can understand that he is not commenting on XEN-1101. That's like asking Otonomy about FX-322. It would be nice to have some update on his RL-81, however. I think the Tinnitus Talk Podcast interview was in May 2020 and there he said that clinical trials probably will start in a year or two...

 

[antonio77]

Prof. Thanos Tzounopoulos needs to answer these question.

Professor Thanos Tzounopoulos has no obligation to you. I don't know who you think you are.

 

[Padraigh Griffin]

I appreciate your effort but what exactly do you hope to gain from the answer?

Both drugs work on exactly the same potassium channels, XEN-1101 has never been tested for tinnitus before, side effects of RL648_81 are unknown, chemical formula of XEN-1101 is a company secret. I'm just curious what extra information you need to know that is so important?

Also, you ask him to "comment" on the drug, but what do you want him to say about it? What information do you want to know that is not available anywhere but from him?

I get that you are frustrated, but I have to agree with @ThomasC here that the email does sound rude. Being impolite definitely won't give you an answer.

I am sure you mean well, but please don't upset one of the few forces working on an actual cure for tinnitus.

Imagine what would happen if we all just start sending him angry emails? Just accept he won't reply to your email.

Can't disagree with you more. He should comment on the other reformulations of Retigabine. Why not?

Just a few lines.

I would like a world expert's opinion on the work of XEN-1101. Is it similar to his compound or not? What is wrong with that? What is wrong... is totally ignoring its existence.

 

[Padraigh Griffin]

I can understand that he is not commenting on XEN-1101. That's like asking Otonomy about FX-322. It would be nice to have some update on his RL-81, however. I think the Tinnitus Talk Podcast interview was in May 2020 and there he said that clinical trials probably will start in a year or two...

No it's not. He is a leading tinnitus researcher and an expert on reformulation of Retigabine. Why not give us a few comments on XEN-1101?? Why not?

 

[OptimusPrimed]

Yes I understand it sounds a little rude. I was hoping not to come across that way too much.

What I can certainly say is RUDE is:

A funded by public money tinnitus researcher that is working on a reformulation of Retigabine NOT commenting at all on a similar reformulation that has near identical potency and selectivity. He has written papers commenting on all potential tinnitus drugs in development, even off label, BUT has never even acknowledged the existence of a compound that is essentially HIS compound. That is not ethical in my humble opinion. To completely ignore the potential of XEN-1101 is just wrong. He is paid by the government. He is a tinnitus expert and has received Department of Defence funding of over $2M in grants.

He owes it to the public to comment on this XEN-1101 reformulation. Does he not? Surely, he could comment on the reformulation of Retigabine by another company? It is for the good of the people and he is a public servant.

It was about my fifth unanswered email. I could not have been nicer in all of my previous ones. What is also rude, is not answering emails with good valid questions.

Also, he is not a business, but a researcher. If I was asking him to comment on competition then I would agree with you, but he is a researcher and should have a total focus on the progress of Xenon Pharmaceuticals for the GREATER GOOD of tinnitus sufferers. Not just his own personal interests. His research.

Prof. Thanos Tzounopoulos needs to answer these question. Why bother spending taxpayers money if XEN-1101 is essentially the same reformulation? Is XEN-1101 the same compound as his? Or are there differences? What are the differences?

If you don't agree with me, then fine, but I feel very strongly about this and he should be quizzed on XEN-1101 in as much detail as possible from my point of view. Again I remind you he is a public servant, paid by US taxpayers.

He has an obligation to help us all, and if that means holding his hands up and saying yea, XEN-1101 is the same as our compound, then he can spend taxpayers money elsewhere in furthering tinnitus research.

Finally, what have you, I and every other tinnitus suffer to gain from his continued denial of the existence of this potential near term treatment in the form of XEN-1101? The answer is nothing. BUT we could gain from some highly qualified insight into the potential of XEN-1101 that may or may not give us hope.

At least I'm out there chasing these guys.

Prof. Thanos Tzounopoulos has made absolutely no progress towards a clinical trial of any significance in a decade. There is nothing but pardon the pun... SILENCE. And taking a nice pay cheque home at the end of the month.

I admit my approach can sometimes be abrupt, but I'm sick of procrastination and non collaboration and just frustrated that my life is destroyed and the 'researchers' are publishing nice papers and everything but not making solid progress.

Please, Prof. Thanos Tzounopoulos, just tell us if XEN-1101 similar to your compound? That is all. Simple question, and needs a qualified answer. Not moving mountains here.

Dude I understand you're suffering, like many, but that email you sent him comes off as rude and passive-aggressive and really does nothing to help the cause of the community. If anything it would push him away from interacting with sufferers.

 

[Padraigh Griffin]

Finally... What if the answer is the compounds are nearly identical? Then why not collaborate with Xenon Pharmaceuticals (if they are interested) and run a PHASE 2 like they did with Mt. Sinai for depression. Minimal funding and let University of Pittsburgh run the trial using the Xenon Pharmaceuticals compound. Skips unnecessary pre-clinical chemist work and gets us our answers earlier and possibly a treatment earlier.

Going solo. Pittsburgh are a decade off and are going to need a larger Biotech to go to PHASE 3 due to funding requirements anyway.

What I see here is a potential opportunity for both parties. The tinnitus market is already large and will be even larger post COVID-19 and generation headphone.

I am trying to get Prof. Thanos Tzounopoulos to maybe consider this.

Last week I spent half an hour grilling Dr. Brendan Conlon. I will speak to Prof. De Ridder in September. I'm not sitting on my ass waiting. If I could do a PhD in tinnitus research I would. I'm trying to provoke some progress and if that means pushing for answers, well yes, I will continue to do it.

Dude I understand you're suffering, like many, but that email you sent him comes off as rude and passive-aggressive and really does nothing to help the cause of the community. If anything it would push him away from interacting with sufferers.

What is rude is not answering another person that has a perfectly valid question. I sent two previous emails and emailed everyone on his team.

Why you guys are afraid of pushing these people with the hard questions that will get progress is beyond me.

I sent the following email to every one of his team:

Dear Dr. xxxxx,

I am an active member of the Tinnitus Talk community, and I am looking for comments on the following drug if possible.

XEN1101 is a reformulation of Retigabine that is 16x more potent at a 20mg once a day dose and has minimal side effects vs placebo and none of the serious side effects of Retigabine. It is also more specific than Retigabine.

It seems to me that this drug may have benefits for tinnitus sufferers and may present a 'bridge drug' until your very own Retigabine reformulation drug is released.

XEN1101 is entering Phase 3 clinical trials in H2 this year. It could be on the market in 2024.

My question is:

Are you aware of this drug? And do you think it is similar to the compound you are working on?

If you could take a few minutes to write a response, our community would greatly appreciate it.

Thanks for the continued efforts.

Kind regards,
Padraigh (Tinnitus Talk)​

All emails ignored. Seven in total. I don't think I was rude in any of those, was I?

Professor Thanos Tzounopoulos has no obligation to you. I don't know who you think you are.

I am a tinnitus sufferer and I am a person.

I am not a US taxpayer but he is publicly funded so he has an obligation to serve the public.

I am totally entitled to ask him his opinion on XEN-1101.

Another God worshipper here.

Why this man won't comment on XEN-1101 is beyond my comprehension. It is unethical. He is a publicly funded tinnitus researcher who is using taxpayers money to reformulate a drug that has already been reformulated.

Anyway, like a lot of doctors or academics (some excluded), yea why answer paupers like me? For crying out loud. They are simple questions and in the interests of all tinnitus sufferers. Just answer the questions. It'll take a minute or two and I made him aware it was not just for me at all stages. It is for ALL OF THE TINNITUS COMMUNITY ON HERE.

 

[StoneInFocus]

Finally... What if the answer is the compounds are nearly identical? Then why not collaborate with Xenon Pharmaceuticals (if they are interested) and run a PHASE 2 like they did with Mt. Sinai for depression. Minimal funding and let University of Pittsburgh run the trial using the Xenon Pharmaceuticals compound. Skips unnecessary pre-clinical chemist work and gets us our answers earlier and possibly a treatment earlier.

Going solo. Pittsburgh are a decade off and are going to need a larger Biotech to go to PHASE 3 due to funding requirements anyway.

What I see here is a potential opportunity for both parties. The tinnitus market is already large and will be even larger post COVID-19 and generation headphone.

I am trying to get Prof. Thanos Tzounopoulos to maybe consider this.

That seems like a total fantasy. I think it's delusional you think you can orchestrate all this just by sending a couple of emails.

I am totally entitled to ask him his opinion on XEN-1101.

You are of course entitled to ask his opinion, but what you are doing is borderline harassment. You even went as far as to contact him on social media? That is totally inappropriate.

Anyway, like a lot of doctors or academics (some excluded), yea why answer paupers like me? For crying out loud. They are simple questions and in the interests of all tinnitus sufferers. Just answer the questions. It'll take a minute or two and I made him aware it was not just for me at all stages.

Again, your questions are not really simple but very very vague. You should first start doing research yourself and come back after you've formulated a clear question for the professor. The fact that you think "It'll take a minute or two" tells me you have an unrealistic views of how these things go. You overestimate your own knowledge on this subject.

It is for ALL OF THE TINNITUS COMMUNITY ON HERE.

Yeah I'm still not convinced why this is so utterly important for the tinnitus community.

No hard feelings man but if you want to speak as a representative for the community you should at least be professional about it. Actually take your time to read up on the literature. You are making a bit of a strange impression here.

I know you mean well, so please don't take offense to this, but this type of behavior can actually make it less likely the Professor or anyone else for that matter responds to mails from other members in the future. So your actions also affect the rest of us.

 

[Nobody19]

All emails ignored. Seven in total. I don't think I was rude in any of those, was I?

Please don't send emails in name of the Tinnitus Talk community. Like others have said, this could backfire on us.

 

[Padraigh Griffin]

That seems like a total fantasy. I think it's delusional you think you can orchestrate all this just by sending a couple of emails.

You are of course entitled to ask his opinion, but what you are doing is borderline harassment. You even went as far as to contact him on social media? That is totally inappropriate.

Again, your questions are not really simple but very very vague. You should first start doing research yourself and come back after you've formulated a clear question for the professor. The fact that you think "It'll take a minute or two" tells me you have an unrealistic views of how these things go. You overestimate your own knowledge on this subject.

Yeah I'm still not convinced why this is so utterly important for the tinnitus community.

No hard feelings man but if you want to speak as a representative for the community you should at least be professional about it. Actually take your time to read up on the literature. You are making a bit of a strange impression here.

I know you mean well, so please don't take offense to this, but this type of behavior can actually make it less likely the Professor or anyone else for that matter responds to mails from other members in the future. So your actions also affect the rest of us.

How the hell do I overestimate my own knowledge on the subject when I am chasing the only person/team in the world that can give us some indication if XEN-1101 could be a potential tinnitus treatment? They surely have a qualified opinion.

I can you tell you one thing. The team at Pittsburgh know far more about the potential of Potassium Channels modulators then me, or even God knows you, who has apparently read all the literature. (I'd say pretty much the same literature I have read as I really do my homework).

But WE know SFA compared to the Pittsburgh team on the potential of Retigabine reformulated as a tinnitus treatment. I don't overestimate my knowledge at all. I have practically zero knowledge whether they will work for tinnitus, I only of the anecdotal reports on here and some animal study reports.

That is all we have. So point me in the direction of the 'literature' that clarifies more. It does fit in with the hyperexcitability theory of Dr. Shore and others as well. Sodium channels accelerators, Potassium Channels, the brakes. Hyperexcitability in the DCN etc. I've read it all bro. I'll take you on any day, but it's all in vein as we know nothing really compared to Prof. Tzounopoulos' team.

Prof. Tzounopoulos gave a great breakdown in his interview on Tinnitus Talk Podcast. Simplified yet detailed enough to understand.

I think you and me and not going to get along here. (Brad) Floyd from True Romance 'Don't you condescend me man... blah blah..." Pathetic to place yourself as an expert. I don't want your opinion dude. You know as much as me which is zilch.

I'm chasing the best man on the planet down for his opinion on the nearest potential drug treatment for tinnitus sufferers worldwide. Coming in 2024 (Retigabine reformulated). Will it help us? What does he think? Is it a possibility? Simple questions that he could answer if he was bothered to do so.

Would people on here not be interested in his opinion on this near term opportunity to relieve our suffering? If you think that is a bad thing, then tell me what is wrong with my questions? It really is not that difficult.

Does he think that XEN-1101 is similar to his own compound? Does he think it may show efficacy for tinnitus? He is the expert on Retigabine for tinnitus, is he not?

The fact none of his team will answers any questions on the Xenon Pharmaceuticals' compound stinks of some bad sh*t to me. To ignore it completely is just weird. It could essentially be the same drug, or in all probability be a better drug due to enhanced resources available to the publicly listed Biotech (whose share price is flying in a down market).

The market and the smart money likes this company and its potential treatments. XEN-1101 being the diamond given the size of the market it could target (if depression trials are positive like the Ezogabine ones were).

What did you do for the tinnitus community today? At least I'm chasing some of these guys down for progress. Like asking Dr. Conlon five days ago would he consider Hubert Lim's EEG timed signal neuromodulation program at Minnesota as a potential Neuromod offering? Asking about TENT-2A. And so on...

My initial 7 emails were professional and courteous and I am entitled to ask him his opinion on XEN-110 on social media too. SFW. Only 2 of those emails were to him and I sent one repeat email to each of his team. PLEASE POINT OUT THE LACK OF COURTESY IN THOSE.

ANYWAY... Just give an answer Prof. Tzounopoulos. Why the hell not discuss this other treatment that could help us all out. Why not? I just can't see why not? Only thing I can think of is that it totally negates their research.

Plus if you can't see a potential tie up between Xenon Pharmaceuticals and Pittsburgh for a tinnitus study, I really don't know what to say to you. It is a blatant opportunity to me and one that could be exploited for all tinnitus sufferers' benefit.

Over and out. We can both saturate ourselves in literature all we want, but it ain't gonna make us experts. Not like this guy...

Please don't send emails in name of the Tinnitus Talk community. Like others have said, this could backfire on us.

Explain how it could backfire on us? I just said I am a member of the Tinnitus Talk community and some of us would like his opinion on XEN-1101. What is the big deal? I also wanted to make him aware that I would be sharing his response, which was an approach I considered to be fair on him.

I said the same to Dr. Brendan Conlon of Lenire last week. I said I'd be posting on Tinnitus Talk. Only fair he knew that in advance of our discussion. He had no problem with it.

Stop being a drama queen.

What's he going to do? Stop all research to spite us because of my emails? FFS. Get a grip.

Anyway, it'll be redundant by the time Pittsburgh releases anything. They are at least a decade away from releasing any compound considering they are still pre-clinical and have no trial planned, and don't have any funding from a partnering Biotech.

The man should just discuss XEN-1101 openly and frankly and give an opinion on it. That is my opinion. Doesn't have to be yours or any others.

God knows. Mountain out of a mole hill here.

Prof. Tzounopoulos doesn't give two sh*ts about giving me his opinion and I have accepted that now. Just a pity I feel. I would really like his amazing expertise to give us some indication on the potential of XEN-1101.

Plus, did all the naysayers on here not read these lines in my 'rude' email?

I hate to be constantly emailing, but us sufferers would value your opinion. I apologise for my persistence!

"I APOLOGISE FOR MY PERSISTENCE!"

Jesus... I really don't know what is wrong with some of ye.

 

[AfroSnowman]

Explain how it could backfire on us? I just said I am a member of the Tinnitus Talk community and some of us would like his opinion on XEN-1101. What is the big deal?

I think it would be better and more accurate to present yourself as an individual sufferer and not as a representative of the Tinnitus Talk community. The deal isn't "big" as I suppose he is already ignoring you, but there may be a time when an actual representative of Tinnitus Talk wants to reach out to him on behalf of our community and he may be less responsive if he conflates it with your individual request.

Though it would be great if he would answer you, I do have to say I get cold emails all the time in my line of work from people asking for info and connection, and sadly I mostly ignore them as I don't have enough time to do my actual work and answer the emails I have to for my direct professional role. It may likely be the same with the good professor.

Peace.

 

[GlennS]

This thread needs a healthy dose of...

 

[Stenis]

Development of an Automated Screen for Kv7.2 Potassium Channels and Discovery of a New Agonist Chemotype

Thanos published this. Seems to help with targeting the right Kv7 channels.

 

[AnthonyMcDonald]

Development of an Automated Screen for Kv7.2 Potassium Channels and Discovery of a New Agonist Chemotype

Thanos published this. Seems to help with targeting the right Kv7 channels.

Gotta keep those paychecks rolling in.

 

[Chinmoku]

Gotta keep those paychecks rolling in.

He is taking forever. Are we still in pre-clinical with the RL drug? Why? He is really risking becoming redundant to some off-label use of the Xenon drugs. I hope things start moving at some point because we have been talking and following this thread for years and people died in the meantime. It's always the same story, none of these guys seems to get the urgency for people who are on the brink. I think, realistically, our only option are the Xenon drugs. Maybe this guy will be able to help the next generations, which is a good thing, but we should emotionally disinvest from his work, it's too far away and moving too slowly on the clinical side.

 

[AnthonyMcDonald]

He is taking forever. Are we still in pre-clinical with the RL drug? Why? He is really risking becoming redundant to some off-label use of the Xenon drugs. I hope things start moving at some point because we have been talking and following this thread for years and people died in the meantime. It's always the same story, none of these guys seems to get the urgency for people who are on the brink. I think, realistically, our only option are the Xenon drugs. Maybe this guy will be able to help the next generations, which is a good thing, but we should emotionally disinvest from his work, it's too far away and moving too slowly on the clinical side.

He's stretching it out as long as possible because it's the only thing that allows him to be able to buy a new Mercedes every year with tax dollars.

 

[Chinmoku]

He's stretching it out as long as possible because it's the only thing that allows him to be able to buy a new Mercedes every year with tax dollars.

I share your frustration, Anthony, but typically grant money cannot be used for buying personal stuff. Unless you mean that he is using his university pay for that, but he has tenure so he has no need to prolong things that much. He would get paid anyway.

I think it's mostly that none of these academics realize the urgency of what they are doing, and maybe they are working on many projects.

With this one, I think the best approach is to let go, I'll never see anything in time to help me, it seems pretty obvious now, maybe you will see something hopefully one day, but he is at total risk of being eclipsed by Xenon. That's a concrete possibility even if not a certainty.

 

[Mentos]

I think it's mostly that none of these academics realize the urgency of what they are doing, and maybe they are working on many projects.

He has tinnitus himself and he mentioned once that he does the research to help tinnitus patients including himself, hence he should share a sense of urgency with the tinnitus community. I think he is similar to Dr. Shore in a sense they both want 100% confidence a drug/treatment they are involved in works at the expense of slow progress.

 

[dan]

He has tinnitus himself and he mentioned once that he does the research to help tinnitus patients including himself, hence he should share a sense of urgency with the tinnitus community. I think he is similar to Dr. Shore in a sense they both want 100% confidence a drug/treatment they are involved in works at the expense of slow progress.

He will find the cure if his tinnitus becomes severe...

 

[ThomasF]

Tinnitus is infuriating at lower intensities as well. Research shouldn't stop until there is a solution for all levels of severity as many are consumed entirely by their tinnitus. It is something that we can fix and just need the people to research it and the money to fuel the engine of progress.

 

[Mentos]

He will find the cure if his tinnitus becomes severe...

Moderate is enough for one to become desperate...

 

[Cory_]

He has tinnitus himself and he mentioned once that he does the research to help tinnitus patients including himself, hence he should share a sense of urgency with the tinnitus community. I think he is similar to Dr. Shore in a sense they both want 100% confidence a drug/treatment they are involved in works at the expense of slow progress.

I think it's good they want to be completely sure what they come up with is probably effective, considering how tinnitus is such a magnet for scam treatments.

 

[StoneInFocus]

Apparently another paper featuring the Prof has been published last month.

If anyone is interested I have attached the PDF to this post.

Abstract
To identify pore domain ligands on Kv7.2 potassium ion channels, we compared wild-type (WT) and W236L mutant Kv7.2 channels in a series of assays with previously validated and novel agonist chemotypes. Positive controls were retigabine, flupirtine, and RL-81; i.e. Kv7.2 channel activators that significantly shift voltage-dependent activation to more negative potentials (ΔV50) at 5 µM. We identified 6 new compounds that exhibited differential enhancing activity between WT and W236L mutant channels. Whole cell patch-clamp electrophysiology studies were conducted to identify Kv7.2. Kv7.2/3, Kv7.4, and Kv7.5 selectivity. Our results validate the SyncroPatch platform and establish new structure activity relationships (SAR). Specifically, in addition to selective Kv7.2, Kv7.2/3, Kv7.4. and Kv7.5 agonists, we identified a novel chemotype, ZK-21, a 4-aminotetrahydroquinoline that is distinct from any of the previously described Kv7 channel modifiers. Using flexible receptor docking, ZK-21 was predicted to be stabilized by W236 and bind perpendicular to retigabine, burying the benzyl carbamate group into a tunnel reaching the core of the pore domain.

Development of an automated screen for Kv7.2 potassium channels and discovery of a new agonist chemotype

 

[addot]

Apparently another paper featuring the Prof has been published last month.

If anyone is interested I have attached the PDF to this post.

Abstract
To identify pore domain ligands on Kv7.2 potassium ion channels, we compared wild-type (WT) and W236L mutant Kv7.2 channels in a series of assays with previously validated and novel agonist chemotypes. Positive controls were retigabine, flupirtine, and RL-81; i.e. Kv7.2 channel activators that significantly shift voltage-dependent activation to more negative potentials (ΔV50) at 5 µM. We identified 6 new compounds that exhibited differential enhancing activity between WT and W236L mutant channels. Whole cell patch-clamp electrophysiology studies were conducted to identify Kv7.2. Kv7.2/3, Kv7.4, and Kv7.5 selectivity. Our results validate the SyncroPatch platform and establish new structure activity relationships (SAR). Specifically, in addition to selective Kv7.2, Kv7.2/3, Kv7.4. and Kv7.5 agonists, we identified a novel chemotype, ZK-21, a 4-aminotetrahydroquinoline that is distinct from any of the previously described Kv7 channel modifiers. Using flexible receptor docking, ZK-21 was predicted to be stabilized by W236 and bind perpendicular to retigabine, burying the benzyl carbamate group into a tunnel reaching the core of the pore domain.

Development of an automated screen for Kv7.2 potassium channels and discovery of a new agonist chemotype

Thanks for sharing! For anyone else following this thread, just note that this study has already been posted here before. Not a dig against you, I still appreciate you for sharing, just wanted other folks to know that this isn't a new paper from Thanos.

I think it's good they want to be completely sure what they come up with is probably effective, considering how tinnitus is such a magnet for scam treatments.

I agree; plus more treatments are good for us. It's great that XEN1101 is further along, but it's very much not guaranteed that it will pass Phase 3. The more chances we have, the better.

 

[Don Tinny]

Tinnitus is infuriating at lower intensities as well.

Really? It was nothing for me. When someone says "I have it too, I hear it when I go to sleep" I always think "no, you don't have it".

 

[ThomasF]

Really? It was nothing for me. When someone says "I have it too, I hear it when I go to sleep" I always think "no, you don't have it".

As I understand it, there isn't really a barrier of entry for someone experiencing tinnitus. The bulk of people do not have tinnitus to an extent that it quite literally fills the brain with noise. I've experienced that when I had a horrible spike back in October 2021. It was so loud that nothing short of placing my ear next to a running bath faucet would touch it. Now it's easier but I can still hear it if I look for it in daily noise.

 

[StoneInFocus]

Thanks for sharing! For anyone else following this thread, just note that this study has already been posted here before. Not a dig against you, I still appreciate you for sharing, just wanted other folks to know that this isn't a new paper from Thanos.

Oops, thanks for noticing, I should've read the thread more carefully. But the paper is behind a paywall anyway, so now anyone without access can read the article too.