Prof. Thanos Tzounopoulos Receives $2 Million Grant

From Retigabine to even SPI-1005 trials, there is evidence of sufferers experiencing a reduction in tinnitus from treatments. Will one or a combination of these drugs “cure” tinnitus for all? Maybe, maybe not. I personally don’t think we’ll see a universal cure until many years out, especially considering the degree of hearing damage is not the same for each person. However, it is very likely that these drugs will provide a significant reduction in tinnitus loudness and severity. And that, in my opinion, provides hope for a much quieter future that appears to be only a few years away.

 

Burning pain yes, and it was all cleared by Retigabine. Now when you think about RL-81 being 15 times more potent than Retigabine... I just hope it works for everyone, because @Telis tried it and it did nothing for him. I tried 50mg and it did nothing for me...

 

I think a lot of us will be happy with a reduction anyway. I don't think anything upcoming will be the cure for everyone. Tinnitus is incredibly complex and has many, many different causes. However, by targeting certain areas and calming down the brain, reduction in tinnitus severity should very well be possible, even within 10 years should even just some of the current trial drugs be successful.

Honestly, all I want right now is for my tinnitus to stabilise and to get to a quiet room only stage. I'll be happy if that happens.

 

From what I’ve read, Retigabine wasn’t very specific and therefore needed to be taken in higher does for tinnitus relief. Meanwhile the new drug will be more potent and more specific.

 

My point exactly... and a lot safer too.

 

Re Retigabine and regenerative medicine don't forget @attheedgeofscience's experience; Low Level Laser therapy, Stem Cell therapy, and Trobalt that eventually got him to the point of being "essentially tinnitus free".

 

Hey Val,

Did you ever get around to trialling LDN for your tinnitus?

 

Where did you hear that the drug is being trialled in Australia?

 

Here's a long shot for you Val.

Did you ever consider trigeminal neuralgia and try treating it with antivirals?

 

An update from Xenon Pharmaceuticals: they recently gave their Q2 corporate presentation, there's a transcript available (see end of my post). Some interesting excerpts I have highlighted here - in the Q&A session they discussed the use of XEN-1101 in treating other neurological conditions. Tinnitus and hearing disorders are mentioned!

"We're exploring indications outside of the focal epilepsy indication, which remains our primary indication for this drug, but there's a tremendous amount of literature that's building in the role of the KB72 and/or 3 channel in neuronal hyperexcitability that underlies a number of interesting neurological disorders where hyperexcitability appears to perhaps drive, for example, apoptosis in motor neuron disease in hyperexcitability through this channel, mediating Pain signaling. Hyperexcitability through this channel thought to have potentially a role in anhedonia and major depressive disorder. And we know these channels are also expressed in the ear and the hair cells, in particular, and the potential for treatment using a Kv7.2 modulator for tinnitus is also of interest."

"So we're looking at a number of these types of disorders. We've been talking about this for some time. It's been an extremely active -- activity at the Company, and we expect pretty soon, I think, to be able to communicate what that plan is. It doesn't detract from the focus being in focal epilepsy, that's the primary opportunity. It remains so. The trial continues to progress well as was updated, tolerability seems very good. We get a high rollover rate, a low drop out rate. So of course, everything is blinded, but data seems consistent with hypothesis going in, the preclinical data, the TMS data, very supportive of epilepsy as an important indication. And of course, there's precedent with ezogabine being the first generation drug working very well in focal epilepsy. So no, the strategy hasn't changed, but we do see some very exciting opportunities outside of focal epilepsy, including, by the way, within epilepsy, but outside of epilepsy, how that may impact long-term from a commercial standpoint, obviously, that's something we would discussed publicly at the right time. But we certainly don't see any shift in our plan today in developing the drugs for focal epilepsy primarily clearly furthest ahead in that indication as well."

https://www.fool.com/earnings/call-...maceuticals-inc-xene-q2-2020-earnings-ca.aspx

XEN-1101 is currently in Phase 2b with results expected in the second half of 2021.

 

I tweeted the WIPF Group for any updates on clinical trials for RL-81 as well as their 2nd generation potassium agonists that they've created based on RL-81. Got the following:

"We got a company to sponsor the development, but the compound is still in preclinical evaluations. Thank you for your interest!"

Not much of an update but it is good to know they've got a company to back them up for development.

 

Guys, @FGG, why is there only ONE researcher working exclusively on curing tinnitus with a pill in the whole world? (Prof. Thanos Tzounopoulos).

Please somebody enlighten me.

 

I don't think that this is accurate. As far as I know there are others who are actually looking at the same thing.

- Hough Ear Institute pill claims it can resolve tinnitus.

- There is a researcher working on a tinnitus and a hearing loss pill with US Department of Defense.

- Some suggest that there could be benefits for tinnitus with a lot of other medicines such as synapse treatments.

 

Well he’s not the only one remaking Retigabine.

I think Xenon, for example, probably assumes that there’s off label demand for it.

 

Sound Pharmaceuticals has a pill (Ebselen) that effects glutamate hyperexcitabilty and while probably not a cure has already reduced tinnitus in their study population (Meniere's).

More on the glutamate effects:

"Ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity."

From:

https://pubchem.ncbi.nlm.nih.gov/compound/Ebselen

It is in phase 3 for Meniere's but they have received an emergency IND to try it on lung inflammation (may have antiviral properties too) for COVID-19 patients so it might be out really soon if it works for that.

Hough's is a pill too but I know your thoughts on them.

 

Wow, that’s really exciting! From what I understand, a drug that reduces glutamate excitability would work on patients with other causes since it’s basically a reverse benzo.

 

Not really a reverse benzo since benzos tip the GABA/Glutamate balance towards GABA. That's why at first benzos usually help until you get receptor tolerance and then it's much, much worse.

This seems like it would reduce the effects of Glutamate without the receptor issues.

 

Well Glutamate slows the nervous system down, so having less of it has the same effect as increasing GABA, that’s why I referred to it as a reverse benzo. It works on Glutamate instead of GABA. I definitely hope this drug comes soon.

 

There's also a researcher in a top secret Chinese facility working on zBomb Blast Pill.

 

Are you being serious or is this a joke?

 

So sorry to keep being pedantic :/...but Glutamate is excitatory, not inhibitory. GABA is inhibitory.

Glutamate is needed across the synapses to transmit auditory impulses but too much Glutamate is too excitatory and neurotoxic.

https://en.wikipedia.org/wiki/Excitotoxicity

 

So what if your Glutamate is normal but you take this drug?

 

The weird thing about Ebselen is that it seems it inhibit both the enzymes Glutaminase and Glutamate Dehydrogenase (I don't think it directly acts on any neurotransmitter receptors). Inhibiting the former inhibits Glutamate production and the latter inhibits Glutamate break down. I'm not sure if the net increases or decreases Glutamate but both these enzyme inhibitions are reversible. Maybe they have pre-clinical data on this but I can't find it.

The drug seems to prevent whatever Glutamate that is present from causing excitatory damage, however by preventing lipoperoxidation:

 

Joke man, joke.

 

Fascinating. So would this only work if Meniere’s was the cause? Is this unique to that disease? So could this help in fighting tinnitus from other causes?

 

I instantly guessed it was but it is the internet where it is hard to tell lol.

 

I don't believe so. I think Meniere's was chosen because it is an easy study population (because until end stage, inflammation / neuroinflammation is a huge component of their syndrome).

The company obviously sees it having more widespread potential because they are testing it for acute noise induced hearing damage, too (like their version of the "bomb blast" pill). And it's being discussed as an adjunctive therapy for all sorts of non-cochlear disease.

To put it another way, there is nothing at all Meniere's specific about the drug and it was obviously a strategic choice (unmet need, relatively easy to assess population).

 

When you say strategic choice, do you mean that the testing on Meniere's was selected because of the thought that this would make it easier to get this treatment through the trials and not anything else?

 

Meniere's has a consistently high inflammatory component. If you are measuring effectiveness of a drug that reduces inflammation they make that easy.

 

What gets much, much worse? I take .5 mg Clonazepam twice daily and it seems to help a lot?