Prof. Thanos Tzounopoulos Receives $2 Million Grant

[Jack Straw]

https://inside.upmc.com/pitt-researchers-grant-tinnitus/

Seems like he is investigating something similar epilepsy drugs.

I remember reading a thread where @Danny Boy said his tinnitus was practically gone after taking epilepsy drugs. I also remember from that thread that Dannyboy mentioned that he was having visual snow problems and in the article they even mention that epilepsy drugs have a side effect of making changes to the retina.

Anyone know more about this research?

 

[EDDTEKK]

Wow that are great news. Hope they will find a way to defeat tinnitus by this medication.
I only know carbamazepine which was working for my intermittent tinnitus pretty good. Unfortunately after 6 months it was losing its efficiency... and the tinnitus came back much worse.

 

[Zeneth]

I've developed visual snow as well.

 

[Don Tinny]

I would not be surprised. I have read texts that describe tinnitus as an "auditory epilepsy". What an ugly thing!

These drug developments of prof. Tzounopoulos, dr. Rauschecker, etc. are about 15 years away, right? I assume they are in a pre-clinical stage and they need to go through phase 1, phase 2, phase 3 ... Rauschecker said "soon", but how soon can it be?

 

[Jack Straw]

I would not be surprised. I have read texts that describe tinnitus as an "auditory epilepsy". What an ugly thing!

These drug developments of prof. Tzounopoulos, dr. Rauschecker, etc. are about 15 years away, right? I assume they are in a pre-clinical stage and they need to go through phase 1, phase 2, phase 3 ... Rauschecker said "soon", but how soon can it be?

Hopefully during the interview with Rauschecker, they will be able to discuss this with him.

15 years is too long.....

 

[Zeneth]

I would not be surprised. I have read texts that describe tinnitus as an "auditory epilepsy". What an ugly thing!

These drug developments of prof. Tzounopoulos, dr. Rauschecker, etc. are about 15 years away, right? I assume they are in a pre-clinical stage and they need to go through phase 1, phase 2, phase 3 ... Rauschecker said "soon", but how soon can it be?

Didn't Trump sign a Right to Try Act a little while back? If we find out that these drugs actually work, something will have to be worked out to get it to us faster. If a drug is working NOW, 15 years is just ridiculous.

 

[Striveon]

I would not be surprised. I have read texts that describe tinnitus as an "auditory epilepsy". What an ugly thing!

These drug developments of prof. Tzounopoulos, dr. Rauschecker, etc. are about 15 years away, right? I assume they are in a pre-clinical stage and they need to go through phase 1, phase 2, phase 3 ... Rauschecker said "soon", but how soon can it be?

15 years?!?! That's insane!

 

[Don Tinny]

15 years?!?! That's insane!

OK, OK...maybe 10 years?

 

[Don Tinny]

If the solution is an IRSS type drug or something like that, I recommend you keep your hormones healthy. These drugs lower libido considerably and it is necessary to have good hormone levels so that they do not affect you too much. It is the advice of a person who took finasteride more than 2 years and has some damage.

 

[WaqasVic]

https://inside.upmc.com/pitt-researchers-grant-tinnitus/

Seems like he is investigating something similar epilepsy drugs.

I remember reading a thread where @Danny Boy said his tinnitus was practically gone after taking epilepsy drugs. I also remember from that thread that Dannyboy mentioned that he was having visual snow problems and in the article they even mention that epilepsy drugs have a side effect of making changes to the retina.

Anyone know more about this research?

Yea Danny Boy's tinnitus got very manageable by that medicine but he got the visual snow from it. I read that from his posts.

 

[Striveon]

OK, OK...maybe 10 years?

YEAH... much better... NOT, they need to hurry up, this is insane

 

[TuxedoCat]

Anyone know more about this research?

Hi Jack, I don't think much more is known about the research than whats in the article you have. Basically, Professor Tzounopoulos and Professor Wipf at the University of Pittsburgh took Trobalt (Retigabine) and redesigned it. They called the new drug, RL-81. RL-81 is more potent and more specific than Trobalt and is thought to have fewer side effects. Trobalt was the epilepsy drug that helped Danny's tinnitus and yes, it accumulated in skin and eyes and turned blue from oxidation. Not quite Smurf blue, but some under the fingernails and colored parts of the eyes. There are pictures on Google Images. After awhile GlaxoSmithKine discontinued selling it.

There is also a second part of the project to look at blocking a receptor called HCN which might prevent hearing loss from loud noise. The Department of Defense is funding the research so preventing hearing loss from blast explosions would be of interest to them.

I don't know that Rauschecker would know much about it, I think he's interested in an animal model, but we'll definitely learn more from his interview. Take care- TC

 

[Autumnly]

Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus
Thanos Tzounopoulos, Carey Balaban, Lori Zitelli, Catherine Palmer
First online: 01 March 2019

Abstract

Spoiler

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.

You can buy this article for roughly 42 euros...

 

[annV]

Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus
Thanos Tzounopoulos, Carey Balaban, Lori Zitelli, Catherine Palmer
First online: 01 March 2019

Abstract

Spoiler

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.

You can buy this article for roughly 42 euros...

I got you the full text article.

 

[Jack Straw]

Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus
Thanos Tzounopoulos, Carey Balaban, Lori Zitelli, Catherine Palmer
First online: 01 March 2019

Abstract

Spoiler

In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.

You can buy this article for roughly 42 euros...

I got you the full text article.

Can someone give me the TLDR?

 

[TuxedoCat]

I got you the full text article.

Thanks @Autumnly, @annV
Can't wait to read!

TC

 

[Johan_L]

When reading this I just think of how far the scientists are from understanding tinnitus and hyperacusis.

 

[Allan1967]

Hi.

I donate to Thanos Tzounopoulos, PhD at the University of Pittsburg.

I asked recently about his research and the direct response I got from Thanos was they are 'currently performing the preclinical development of two lead candidates'.

I have an idea what that means but can anyone explain further?

Thanks.

 

[JohnAdams]

Hi.

I donate to Thanos Tzounopoulos, PhD at the University of Pittsburg.

I asked recently about his research and the direct response I got from Thanos was they are 'currently performing the preclinical development of two lead candidates'.

I have an idea what that means but can anyone explain further?

Thanks.

It means they aren't sitting around going "aaaaaddddurp" like almost everyone else. "Candidates" in this case are like drugs or something.

 

[Clint Azzopardi]

Thanks @annV for the article.

 

[Allan1967]

It means they aren't sitting around going "aaaaaddddurp" like almost everyone else. "Candidates" in this case are like drugs or something.

My interpretation is that they have two types of drugs they are working on which are at the pre-clinical trial stage which means they are still a fair way out from being tested on humans and probably even further away from being released.

However, at least it's something.

 

[grate_biff]

I have an idea what that means but can anyone explain further?

It means some guinea pigs are having their tinnitus solved, hopefully without getting blue in the face and without visual problems.

 

[Piney]

He said he needed a million to find a cure. Well there's 2 million, let's do it.

 

[JohnAdams]

He said he needed a million to find a cure. Well there's 2 million, let's do it.

 

[Allan1967]

It means some guinea pigs are having their tinnitus solved, hopefully without getting blue in the face and without visual problems.

It's a great time to be a guinea pig.

 

[chuto]

My interpretation is that they have two types of drugs they are working on which are at the pre-clinical trial stage which means they are still a fair way out from being tested on humans and probably even further away from being released.

However, at least it's something.

In one of his articles named "LI S, KALAPPA BI, TZOUNOPOULOS T (2015) Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus." they mention two possible treatment ways, maybe he was referring to these 2 types of drugs:

"now show that exposure to excessive noise causes a reduction in KCNQ2/3 activity in the exposed mice. However, in animals that successfully avoid developing tinnitus, KCNQ2/3 activity spontaneously recovers over the course of a few days. This recovery triggers a reduction in the activity of another type of ion channel, known as the HCN channel. The combined flexibility of KCNQ and HCN channels prevents tinnitus-associated hyperactivity in the fusiform cells.

Drugs that increase activity of KCNQ2/3 channels, and/or reduce activity of HCN channels, could thus boost resilience to tinnitus. In the future, targeting both channel types at the same time could provide an effective treatment with minimal side effects."​

 

[smapti]

Thought I would chime in on this one and show you a reply to a recent e-mail from Dr.
Tzounopoulos. As far as I see it, he is our greatest hope. Everything else is just so...well...1972.

Hello -

I know you get a lot of questions about this, so I'll be brief:

(1) Will RL-81 have a clinical trial? If so, when will it start?

Yes. We are currently performing preclinical studies (toxicity, etc)


(2) What is the possibility it will work for tinnitus sufferers?

Do not know for sure, but I am optimistic based on our research so far


(3) If it works, when do you project it could be on the market? 5 years? 10 years? Not in our lifetime?

Hard to predict the future – I do not plan to leave the planet before we have FDA approved medication for tinnitus

 

[Hayls32]

Thought I would chime in on this one and show you a reply to a recent e-mail from Dr.
Tzounopoulos. As far as I see it, he is our greatest hope. Everything else is just so...well...1972.

Hello -

I know you get a lot of questions about this, so I'll be brief:

(1) Will RL-81 have a clinical trial? If so, when will it start?

Yes. We are currently performing preclinical studies (toxicity, etc)


(2) What is the possibility it will work for tinnitus sufferers?

Do not know for sure, but I am optimistic based on our research so far


(3) If it works, when do you project it could be on the market? 5 years? 10 years? Not in our lifetime?

Hard to predict the future – I do not plan to leave the planet before we have FDA approved medication for tinnitus

He might live to 90! Here is hoping for something in the next few years

 

[DaveFromChicago]

I have lately been considering the similarities between the history of treatments for migraines versus those for tinnitus.

Before the release of the drug Maxalt, there were as many initially promising but utterly ineffective "therapies" for migraines as there now are for tinnitus.
I have migraines, and nothing actually fully reached and dissolved the pain before the development of amitriptyline (Maxalt).

I fervently hope that Lenire yields real effectiveness, but I have always intuitively felt that the ultimate solution will reside in drug innovations.

 

[Fabrikat]

It's good that he specifies tinnitus in his research aims. I recall his interest in modifying drugs like Trobalt, was to treat epilepsy, with tinnitus as a happy side benefit.

But at this stage this looks like it's a decade away. I like to think we will have other options before then.