Sound Pharmaceuticals (SPI-5557 & SPI-1005)

More for hyperacusis/noxacusis.

 

Most of the discussion on this site regarding sodium channel blockers has to do with treating hyperacusis, not tinnitus.

 

@Croaker, @FGG, oh sorry, I didn't know that. Thank you for answering.

 

I inquired about about joining one of their trials awhile ago, and I got a response stating that they are not currently doing any trials for tinnitus and hyperacusis but that they might next year. I thought this may be of use to you guys.

 

Unfortunately indeed.

Sound Pharma advances pivotal Phase 3 clinical trials in Meniere's Disease

Quote from source:

“Additionally, SPI-1005 treatment reduced tinnitus perception or tinnitus loudness (TL) by a statistically significant difference (p-value <0.05 using Fisher's Exact test) when compared to placebo. Reductions in TL averaged 1.4 pts in the 400 mg group vs 0.7 pts in the placebo group (30% reduction vs 10% reduction, p<0.02). These Phase 2b data confirmed an initial finding of the Phase 1b data, that SPI-1005 can reduce tinnitus loudness by clinically relevant levels. These improvements in auditory function further support the use of SPI-1005 to treat sudden hearing loss, noise-induced hearing loss, and age-related loss where sensorineural hearing loss and tinnitus are prominent features.”​

I didn't ask my doctor cause they are shit. You have a company called myTomorrows. They are situated in Amsterdam, but work worldwide. They help with getting drugs early.

myTomorrows

Good luck. I will fly off again. I try to spend no to little time on this forum, because it's not good for my mental health.

 

Oh goodness, it doesn't look promising that they will respond then. Friggin' devils they are! And us all suffering!

Thanks for the response. I hope sometimes soon we can manage to give it a try!

 

Getting desperate, I can't go on, I need to try everything. Unfortunately from this thread it seems that getting Expanded/Compassionate Use for Ebselen is not working, as they ignore emails and requests. So unless one can wait probably 3 to 5 years (and I can't at this rate of worsening) one needs to source Ebselen via web.

400 mg BID seems to be the best guess at the moment. 2 weeks of treatments at 800 mg a day would be less than 15 g. $1250 is affordable to me, but:

1. How does it come? Powder? Liquid? Pill?
2. If powder, how do we take it? With water? Other solvents? How do we administer it?
3. Could purity be an issue and the residual chemicals poison us?
4. Do we need to get it tested?

Other things to consider if trying it?

 

My guess is a lab is not going to bother pressing it into tablets for you, so probably powder.

I personally would 3rd party test anything that comes out of a Chinese lab first but that's just me. It's not a requirement and is strictly a matter of trust. Products out of China have a mixed reputation.

My hunch is you wouldn't need a solvent but that's a good question. There was an anecdote someone reported here, does anyone know how they took it?

I think a Tinnitus Talk member ordered it already. Hopefully they can provide an update because that might answer some of these questions...

Edit: an extra bit that might be a factor in your case, @Chinmoku , is that I might ask your neurologist about the lithium-like effects on Inositol phosphate phosphatase. Ebselen is reportedly much safer than lithium but it's being tested on bipolar patients for this indication (though at a higher dose than used here). The reason i bring this up, is that I read reports that many people with bipolar (I know this isn't your problem) take both lithium and Benzos so there probably is at least some info out there on whether this aspect effects withdrawal, even at the lower dose here.

 

Ebselen can break down skin pigments and reduce melanin in the body, which might increase the risk of cancer

In yeast, ebselen may damage DNA and turn off genes that help reduce the damage

High doses of ebselen can kill specific cells (HepG2 cells, hybridoma cells)

Ebselen causes calcium release from the mitochondria, disrupting mitochondrial function. This may result in loss of energy and quicker aging.

Source:
https://selfhacked.com/blog/ebselen/​

 

Does anyone have any guesses on how that would impact noxacusis and the release of ATP which triggers the afferent nerves? Honestly, if it just killed those cells releasing the ATP I’d be happy, but I certainly don’t want an increase of ATP!

 

That blog is all over the place. In one place it says the drug is safe and well tolerated and then it suggests it could make you paler and more prone to skin cancer.

Definitely don't take very high doses I guess though. Just in case.

 

Give me all of that if it improves noxacusis.

 

My thoughts exactly.

 

Are there really zero labs out there selling Ebselen to consumers?

I scoured the internet and found some websites but they either looked shady or were only selling to researchers.

There are people here willing to shell out $10k just to see if it works and we still haven't managed to find a reputable lab.

 

This company is legit, however unlikely to sell direct to the public:

https://www.medchemexpress.com/Ebselen.html

Probably the same for any legitimate source. Of course, you could always create your own lab business and place an order then

 

With the recent review from the University of Manchester identifying a possible association with COVID-19 and long haul COVID-19 causing/exacerbating hearing loss, tinnitus, and vertigo, I feel like it'd be a great opportunity for Sound Pharmaceuticals to trial SPI-1005 in treating these vestibular issues in addition to their on-going trials for moderate and severe COVID-19 hospitalizations.

If SPI-1005 could treat both, I could see them getting Emergency Use Authorization fairly easily.

I've reached out to Sound Pharmaceuticals about this.

 

They're about to start Phase 2 clinical trials on COVID-19.

 

Their current COVID-19 Phase 2 trials seem to focus more on non-vestibular symptoms of COVID-19, oxygen, and oxygen saturation. They haven't updated their Phase 2 trial pages since November which lists the trials as ending in April 2021.

SPI-1005 Treatment in Moderate COVID-19 Patients

I'll probably reach out to the Principal Investigators to find out exactly what the statuses are.

My thought was that they should open up additional clinical trials looking at the treatment of vestibular issues due to COVID-19 and long haul COVID-19.

 

Imo it doesn't really matter under what indication it gets released, just that it does.

There's a pandemic going on, we can always convince a doctor to give it to us. I think it's even going to be OTC.

 

The point I'm trying to make is that the more beneficial SPI-1005 proves to be for COVID-19 and COVID-19 symptoms, the faster and more likely it'll be released. I literally want Sound Pharmaceuticals to strike while the iron's hot. We both want the same thing.

 

You're totally right. What do you think about Ebselen for us chronic tinnitus sufferers? Do you think it could help?

 

Since causes of chronic tinnitus are so varied, I think it'll help a subset of sufferers. Regardless, I'm going to try it out whenever it's released.

 

I recall some of the participants that saw improvements had age-related hearing loss, which has a NIHL and SNHL component.

 

Someone get me up to speed:

We think that Ebselen has an anti-inflammatory effect when taken orally that somehow may reduce the symptoms of tinnitus/hyperacusis/noxacusis? It is believed this is the case because subjects with Meniere's Disease saw a reduction in their tinnitus annoyance/loudness?

Now Sound Pharmaceuticals is trying to get the drug pushed through trials because they believe Ebselen helps with patients respiratory inflammation from being infected with COVID-19? Does this mean that they are in the acute stage of the COVID-19 infection? Or are these "long-haulers" that have recovered from COVID-19 but still have breathing problems? Or both?

Is the thought here that if Ebselen is approved by the FDA for COVID-19; it could be accessed off-label for hearing loss conditions in a pill form?

Also, what's the deal with people having labs make Ebselen for them? I'm all for experimenting with drugs... are the people on here leading that deal planning on structuring documenting their experience with their "lab-made" Ebselen in a scientific manner? If you're going to spend that kind of jack, at least take the time to construct some solid data. The last thing everyone needs is another "it worked for me, plus all the other supplements" thread that leads to nowhere.

 

This is what I understood as well.

The main protease of the coronavirus SARS-CoV-2 is a potential drug target, and last year a screen with over 10,000 compounds identified Ebselen as a particularly promising inhibitor. This was published in Nature. In current research on the inhibition for SARS-CoV-2, Ebselen can serve as a promising lead compound, if the inhibitory effect is confirmed in vivo. On top of this, potential beneficial effects of Ebselen in COVID-19 are ascribed to things like attenuation of inflammatory oxidants and cytokines. In other words, I don't know if I'm fully up to speed but they see several ways it can help against COVID-19 at a more or less fundamental level. I think it makes sense to try it also for long COVID-19 but someone else may be more up to speed. I haven't read much of late as the torture is crazy.

Yes, many of us hope this happens.

People are suffering at unimaginable levels and before resorting to very drastic measures they want to try everything they can. These people struggle to take a bus or leave home and are hardly in the mental space to organize this as a rigorous controlled experiment or a private clinical trial. They only have energy left for a few last desperate attempts. However I agree that people whose suffering is more reasonable should get organized and research this thoroughly.

 

Ebselen is not strictly an "anti-inflammatory drug" and, even in that capacity, it is not anti-inflammatory in the way anti-inflammatory drugs usually are (i.e. primarily affect chemotaxis and migration of neutrophils and vascular permeability). Actually, Ebselen may have some direct effects on vascular permeability, too, but it is more akin to the effects of a drug like Amlodipine (more on this in a bit).

In terms of why it's so confusing as to what Ebselen does, it's because it's an extremely odd drug with a lot of varied targets. Even the chemical structure of it is extremely unique:

The Weirdness of Ebselen

Interestingly, Jonathan Kil from Sound Pharmaceuticals actually commented on this blog post:

"The Daichii ebselen stroke trials were probably the most advanced clinically, but were limited due to the sample size, the nature of that disease, and the approval of tPA in 1997. In addition, I thought you maybe interested in our ongoing clinical trials in sensorineural hearing loss and tinnitus with SPI-1005. We have completed a Phase 1 and Phase 2 in acute noise induced hearing loss which were highly successful. We are currently enrolling a Phase 1/2 in Meniere’s disease (hearing loss, tinnitus and vertigo) and preparing to enroll two ototoxicity studies involving chemotherapy or antibiotic receiving patients. In several different models of acute neurotologic injury, we and others have shown that ebselen is highly otoprotective through its action as a GPx1 mimic and inducer. This later effect is somewhat dependent upon Nrf2 activation. My feeling is that ebselen will find a home in diseases where decreases in GPx activity result in the establishment of acute injury and the progression to chronic disease and/or in specific organs where GPx is the dominant catalytic antioxidant enzyme such as the inner ear, retina, lung and some areas of the forebrain."​

What he seems to be saying is that he believes Ebselen has a mechanism of action in a variety of acute injuries and also in areas where Glutathione Peroxidase is involved in chronic inflammation: inner ear, retina, lung and parts of the brain.

They are testing it on chronic conditions of the brain, for instance (bipolar disorder, Alzheimer's, as a preventative for Parkinson's, which has been tested in primates, and could maybe help prevent or slow down progression) and plan to test it acutely for COVID-19 lung disease (it may help the long haulers, too, we don't know).

In rodent studies, it seemed to show effects on both tinnitus and (I assume loudness) hyperacusis.

So, what are some of the known targets of this drug?

-- Glutathione peroxidase inducer (this helps with oxidative stress and neuroinflammation) as Jonathan Kil mentioned above

-- It is also shows effects as a cytokine modulator:

Ebselen--an in vivo immune response modifier

Of note, TNF-Alpha was a key cytokine in the Dr. Bao studies.

-- In rodents at least, it's a voltage-gated calcium channel blocker (this would have vascular effects)

-- In rodents, it affects some potassium channels as well (this was an acute rodent study as well) but the only study in people (it was a diabetic vascular study in patients that did not have neuropathy or retinopathy), showed it did not have an effect. This at least shows that, in chronic diabetes, it does not have a restorative vascular effect (which is very specific and not in the scope of what Sound Pharmaceuticals is trying to do).

-- It affects the NMDA receptor and dampens Glutamate hyperexcitabilty effects through multiple mechanisms (redox effects? lipoperoxidase effects?)

-- It also may have anti-depressive effects similar (but reportedly safer) than lithium due to inhibitory effects on inositol monophosphatase:

A safe lithium mimetic for bipolar disorder

-- It also may affect acetylcholinesterase activity (like Huperzine A being studied in China for age-related hearing loss related tinnitus):

Pre-treatment with ebselen and vitamin E modulate acetylcholinesterase activity: interaction with demyelinating agents

If all of this seems confusing, it is because it is. I have never personally seen a drug with so many different targets.

It's one reason this drug has so much potential but also perhaps why it should only be tried as a last resort for people who are at the complete end of their rope until we get more safety data (even if so far, it looks good).

I want to add too, for anyone trying this on their own. More is not always better in terms of efficacy. In fact, the 400 mg group did much better than the 600 mg group in this study:

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial

 

Thanks for the excellent summary of Ebselen.

Apologies if this has already been answered, but for those who want to try Ebselen, is it available? If so, where can I get it please?

 

You have to contract a lab to make it for you. In the US, they only sell to "research labs" but China can be less strict about this. I would get an outside lab to test anything you get from China.

I don't know which lab to recommend.

If you could possibly wait, their drug is pretty far along in trials.

 

If the safety profile continues to be good, do you think it's a good idea to get at least one round (28 days, 400 mg)?

 

That's up to you to research and decide yourself.