UK launches drug trial to tackle fatigue in long covid and ME/CFS

[godlovesatrier]

https://www.theguardian.com/society...drug-trial-tackle-fatigue-long-covid-patients

Let's hope this is as good as it looks! Any drug is better than no drug if it works.

The first trial of a drug to target the fatigue and muscle weakness experienced by more than half of people with long Covid has been launched in the UK. It is also the first drug trial in long Covid patients who were not hospitalised during their initial infection.

The drug, called AXA1125, targets cellular power plants called mitochondria, which it is thought could be dysfunctional in the subset of long Covid patients with severe fatigue. If successful, it could pave the way for similar trials in patients with other forms of post-viral fatigue, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

 

[Treeman]

Cool ,

 

[godlovesatrier]

To be honest I thought it was a joke. I'm amazed we've hit the mainstream so soon. Sincerely hope the trials don't absolutely flunk. Any drug we can try makes doctors and all sorts of medical people THINK about the disease. It opens a huge conversation around fatigue - even if it's only one symptom. Fingers crossed.

 

[gregh286]

Sounds really fantastic focus on mitochondria function.

 

[gregh286]

The study will compare the effects of AXA1125, an orally active mixture of amino acids.

A super duper protein shake

 

[godlovesatrier]

It's aminos?! Bloody hell hope it's more than that.

I can't take bcaas anymore. They cause terrible anxiety. Glycine and choline however definitely ameliorate fatigue in combination with pacing and loads of other things.

Well that's poured water on my enthusiasm if it's aminos. But the conversation will still be had which is very important. Progress is slow sadly.

 

[gregh286]

Seems so
https://me-pedia.org/wiki/AXA1125

5 aminoz and our aul friend NAC.
Big trial for a protein shake. Jesus what next.

 

[Wishful]

Notice this part: "which it is thought could be dysfunctional". To me that sounds like they have no idea whether limited ATP production is the cause of the fatigue. Boosting ATP production sounds good for countering fatigue, and they have nothing else to offer, so they'll push this. I haven't seen any reasonable evidence that ATP production is limited in ME, so I'm not expecting this drug to work.

 

[godlovesatrier]

There's that too. I just hoped it might give severe patients a tiny bit of life back. Not so sure now.

 

[ZeroGravitas]

Well that's poured water on my enthusiasm if it's aminos. But the conversation will still be had which is very important.

It is kinda wild seeing these things pop up in the national press. And yeah, they say it's not expectected to be curative "I don’t think this one drug will be the solution to everything", so modest expectations at best.

But I wouldn't be too down on "just aminos". I mean, they can be 'burned' for energy directly, and assist in using the other macro-nutrients. But the *relative* balance of intake can be very potent, in modifying the environment cells find themselves in. And various metabolomics studies showed pwMEcfs have substantially reduced levels of many AAs in serum (I've seen this myself in a test).

Axcella show findings of significantly altering immune system signalling and RNA expression (part of their information sheet linked by MEpedia):

https://me-pedia.org/wiki/AXA1125 5 aminoz and our aul friend NAC.

Right, was about to link MEpedia myself; it's also called LIVRQNac and the five amino acids are "arginine, glutamine, isoleucine, leucine, and valine" plus "N-acetylcysteine (NAC)"

In May, for their phase 2b trial for "nonalcoholic steatohepatitis (NASH)", they're talking about administering...: "[...] either 45.2 or 67.8 grams per day of AXA1125 or a matched placebo in two divided doses for 48 weeks [...]" Which is, I think, almost an entire RDA of protein (dry weight)! So really drastically changing one's balance of metabolites.

Personally, I can't tolerate glutamine or NAC in regular doses (maybe liver detoxification; just causes next day fatigue like histamine). And I'm also very sensitive to just a few mg of Tyrosine (in making dopamine -> adrenaline, etc, I assume). So, those quantities seem daunting.

 

[BrightCandle]

That is a lot of amino acids. I certainly feel somewhat better on higher protein intake but I doubt I get that remotely that much from meat protein alone. I have used EAA and BCAAs and not found much benefit but I never tried these sorts of quantities.

 

[ZeroGravitas]

► Oh, and I came to the forum to see if I could search up talk of a treatment like this from a few years ago...? Maybe there was a Cort blog, etc? Different company? Somewhat different mix of AAs probably.

► Then, regarding NAC, MedCram has talked about it repeatedly as a targeted treatment for acute Covid (I went into much more detail in this thread). Where he was theorising (back in May last year) that the virus's destruction of ACE2 surface protein destroys their anti-oxidant function. So for the rate limiting substrate in making glutatione (the master antioxidant) NAC is very relevant.

Also, NAC itself, helping to break down excess clots in circulation; MedCram was talking about von Willibrand's factor well before all this HELP aphoresis stuff. That might also be relevant to ME/CFS, if Dr Asad Khan is right to in asserting we have excess micro-clots too. I'm very dubious of that being the be-all, but am aware of a tendancy towards thicker blood and clotting (having failed to fill a tiny home blood test vial today, after lancing my hand 4 times...).

 

[BrightCandle]

This is a lot of EAA to take in. That is more than a scoop of the stuff and that is twice a day. Its vile stuff, one of the reasons I never stuck with it is even a protein shake can't mask the distinctive flavor. By the looks of things their formulation is very similar to an EAA mix I have so unless they work out how to make that palattable they are going to have some drop outs from that trial!

PS Yuck! Do not mix raspberry protein shake and EAA, it just makes it worse.

 

[godlovesatrier]

I can't tolerate glutamine or tyrosine either. They just amp me up make me violent and give me terrible anxiety. Glutamine gives me really dreadful chest pain.

So I totally get those reactions. I really hope this thing there working on works though.

But yes 45 to 60 grams is a lot! Wonder what it breaks down as individually.

I take 6g nac per day and 45g glycine. About 600mg choline as well. Could prob take more choline but since I stopped lion's mane don't suffer with depression anymore.

 

[BrightCandle]

arginine, glutamine, isoleucine, leucine, and valine

Bulk EAA mix contains Leucine, Valine and Isoleucine (plus other aminos) but its missing the glutimine and arginine. Its also disgusting.
Bulk BCAA contrains Leucine, Isoleucine and Valine as well also missing glutamine and aginine.

Applied Nutrition BCAAs adds Glutamine but the citrulline and malate and other components are not wanted.

So I think its plausible at least we might be able to find a powder mix of BCAAs that contains the same mix of ingredients although its unlikely to be ideal and as limited as that in the trial OR you could take something like the Bulk BCAA and add onto it L-glutamine and L-arginine in pill or powder forms. I think its perfectly doable anyway, I'll keep looking and if I find something that looks better than that then I'll post back.

 

[ZeroGravitas]

45g glycine

4.5g, you mean, right..?

Its also disgusting.

Yeah, I'd liken bulk BCAA to clothes detergent powder; no idea how one could physically consume that quantity of the awful hydrophobic stuff...

 

[mitoMAN]

this is most likely a fail trial. Ingredients are common supplements, sadly.

 

[andyguitar]

The Guardian must have been having a slow day for news to write about this!

 

[godlovesatrier]

Slight mistake on the glycine sorry! See below. It sustains glucose release to our muscles. If I don't take it a crash is more severe. If I do take it it's cut back dramatically.

5g glycine 4 X a day so 15g a day.

But I'm also taking 2500mg beta glucans twice a day so 5g beta glucans per day.

Once you can tolerate large doses it's worth taking them to sustain the good effects.

But I've got a cold and I feel like shit and have had most symptoms flare so aminos for me would never be enough.

 

[godlovesatrier]

@andyguitar indeed! They are always terrible these days. Bastion of nothing...

I'm watching Fifth Estate in despair...