Prusty talks about his upcoming research on a podcast

[Osaca]

Yes, you are correct: in mathematics, physics, computer science. But this is not true for medicine or biological sciences. Medrxiv didn't start until June 2019, and Biorxiv earlier in 2013, but had slow growth until 2017.

Yes, especially in medicine there is a lack of understanding what the right thing to do is, but it seems they will get there eventually. It's particularly shameful that ME/CFS and Long-Covid researchers, who have been very public about how many things are wrong with the peer review process and that publishers have too much power, themselves don't want to submit to the Arvix. They are digging their own grave. With the whole fuzz Prusty made with the announcement and publicly stating his concern about journals and editors, not submitting to the Arvix is ridiculous.

The last time I spoke to a ME/CFS researcher, she told me how they had very relevant new findings and that she wants to make them accessible to everbody with their pre-print. When I told her, why don't you just do it, and submit to the Arvix, she looked at me as if she'd just discovered dark matter.

 

[Jackb23]

There is one IgM enriched immunoglobulin available called Pentaglobin.

https://www.transmedpharma.com/our_products/pentaglobin/

When I searched PR for Pentaglobin, only 2 messages came up. Two ME patients tried Pentaglobin and both of them responded extremely well. One of them said, it gave him total remission for two months.

https://forums.phoenixrising.me/thr...atment-by-any-doctor.35949/page-3#post-567065

https://forums.phoenixrising.me/threads/what-happens-with-ivig-therapy.78117/#post-2238885

Sign me up.

 

[Jackb23]

I did a metabolomics study a few years back and my fibronectin was not found to be abnormal. I do not know if they were screening for it, however.

Thread is here: https://forums.phoenixrising.me/threads/mass-spectronomy-testing.61739/#post-1004635

 

[Osaca]

I did a metabolomics study a few years back and my fibronectin was not found to be abnormal. I do not know if they were screening for it, however.

Thread is here: https://forums.phoenixrising.me/threads/mass-spectronomy-testing.61739/#post-1004635

Maybe you can pop the lab that did the test a message and ask them?

 

[Treeman]

I wrote on page 3 of this thread how immunoglobulin therapy (imt) is a know treatment what can resolve fatigue, although it's primary aim is to reduce persistent damaging infections.

I have been diagnosed with hypogammaglobulinamie along with me/CFS. I first got Ill age 6, am now 57 and the diagnosis didn't arrive until age 52. I only began imt 4 months ago after my MP got involved and my daughter was also diagnosed with the same illness after it was triggered by a COVID infection. At this time it's only a 6-12 month trail.

We are now undergoing genetic testing for a primary immune disease.

I'm in the UK and the NHS is only interested in treating with imt if you have persistent damaging and potentially life threatening chest infections.

I use cuvitru which only contains IgG. Prusty mentions using a treatment with IgM, but in grander scheme of this may not be critical.

Even in immune treatment medicine they can't explain how the immune system works. My daughter has a much worse immune level than me with a similar immune response to a vaccine challenge, however I have much worse fatigue. Why? And there are other stories I have seen that are similar, why?

My advice to everyone would be to have immune values checked. You may end up getting the treatment that could unlock good health.

any product of imt could benefit. From memory IgM are the first antibodies to be formed and attack infections, but long term suppression of infections are by IgG, could this be an indication why the 2 previous examples on this forum had initial success with enriched IgM?

I also understand the longer you've been ill the longer it will take to clear the infections and fatigue. So imt is really a long time commitment, however some find it can kick start the immune system back in to life.

so far in my treatment I have lost the persistent throat, nasal and sinus inflammation and my asthma has now gone. It appears to me the asthma was caused by a persistent infection I couldn't clear.

There is a lot of accepted medical research for the immune system, far more than me/CFS , use it and as a first stage get your immune levels checked.

 

[SleepingGirl]

Didn't Prusty make mention that there were current medications/treatments already available to possibly reverse this? I'm not sure if what he has found has fully been dropped or not, I've been following along with the thread but kind of confused if everything has been revealed fully or not. I've finally been able to see a disease specialist so was hoping I could get him to let me try some experimental things but maybe that's just wishful thinking, lol.

 

[Osaca]

Didn't Prusty make mention that there were current medications/treatments already available to possibly reverse this? I'm not sure if what he has found has fully been dropped or not, I've been following along with the thread but kind of confused if everything has been revealed fully or not. I've finally been able to see a disease specialist so was hoping I could get him to let me try some experimental things but maybe that's just wishful thinking, lol.

I don't think he held back. I think the paper will be similar to what we heard + the proper data. The data is the important part. He mentioned potential treatments that already exist like IGAMs, Immunadsorption, cell transfusions, antivirals and there's even other things he didn’t mention. When he was talking about potential treatments, it's less about having something that will work, but something that could work if his theory were to be correct. Just imagine he’d found something like a virus having the same mechanism like HIV, permanent nerve damage or some form of demyelination. Then we’d know there wouldn’t exist a treatment. Now we know if his theory were to be correct there would be potential therapies that could address it. However, even in that scenario it would still have to be analysed how far upstream or downstream his theory takes place.

 

[Tsukareta]

I might be misremembering but early on it sounded like he was working closely with specific ( severe ? ) patients and trying to raise the 'missing protein', and that there were some treatments that had previously been effective in ME/CFS. He said it may be possible to raise this protein but it would be a slow process. Is that what you are unhappy about Osaca ? moving of goalpost, overhyping and vague talk. I don't understand the formalities of the scientific publication process. What I can say though is it sounds like they knew about the Fibronectin for a while and held onto that and kept it private.

 

[Osaca]

I might be misremembering but early on it sounded like he was working closely with specific ( severe ? ) patients and trying to raise the 'missing protein', and that there were some treatments that had previously been effective in ME/CFS. He said it may be possible to raise this protein but it would be a slow process. Is that what you are unhappy about Osaca ? moving of goalpost, overhyping and vague talk. I don't understand the formalities of the scientific publication process. What I can say though is it sounds like they knew about the Fibronectin for a while and held onto that and kept it private.

I don't have the impression that he was trying to reintroduce the "missing protein" in specific patients, but interviews are very open for interpretation and our minds start to wonder about what he might be saying. I for example though that the slow process was rather referring to fixing all the downstream issues rather than reintroducing the "missing protein" which would be comparatively quick.

I'm actually not unhappy with anything, apart from the fact there's no preprint, which something everybody should be upset about imo. I'm also not unhappy, that in my impression, a shift happened a bit from Herpesvirus reactivation and mitochondrial fragmentation towards low natural IgM, Fibronectin and acute Covid, it's just something I noticed. So I was wandering if others noticed it too and whether it might be, because he recently got hold of a lot more samples, which seems to be the case. If anything more samples are a great sign. I too do think they knew about Fibronectin for some time and held it private, probably for very good reasons, that is nothing I'm upset about.

 

[serg1942]

After listening to Dr. Prusty's interview I really cannot understand why we are not as the whole ME/CFS community persuing clinical trials with anti-purinergic therapy.

On the following post I have compiled a lot of literature indicating that anti-purinergic therapy seems to revert the abnormalities described by Dr Prusty and Dr Phair as part of their HHV-6/Fibronectin1 and itaconate/IFNa etiopathigenic models for ME/CFS, respectively:

https://forums.phoenixrising.me/thr...d-abnormalities-in-me-cfs.90173/#post-2435206

Note that anti-purinergic agents have shown to inhibit fibronectin1 expression, to increase mitofusin-1 expression, to inhibit viral replication/infection (HHV-6, CMV, HIV, HHV1, sars-cov-2,etc.), to inhibit mitochondrial fragmentation, to restore Kreb's cycle abnormalities and antioxidant status (GSH/GSSG, NADH/NAD+), or even to increase total immunoglobulins.

For sure trying to take filgotinib to inhibit the JAK-STAT signal, an IFNa inhibitor, and a TLR-targeted intervention could work, as proposed by Dr Phair. And similarly IVIgG and immunoadsortion therapy seems reasonable, as proposed by Dr. Prusty. But I can't get my head around the fact that nobody is proposing anti-purinergic therapies, after reviewing the literature.

 

[Jackb23]

Maybe you can pop the lab that did the test a message and ask them?

Just emailed them.

 

[Vlad83]

I don't have the impression that he was trying to reintroduce the "missing protein" in specific patients,

I did get an impression from his earlier interview and tweets that a missing or depleted protein was causing another protein to go up and cause mito fission. All that sounded like cytoplasmic proteins (like Drp1 and something else). But maybe what he really meant was Fibronectin and (n)IgM-FN, with the latter being the "missing protein". It is a bit strange to call antibodies a protein, IMO, but maybe we was just being vague to avoid revealing too much early on.

Overall I must say I was disappointed and underwhelmed with his latest info from Cambridge. He had created high expectations by his initial announcements. Now it sounds like they "may" have found something very important (high fibronectin and (n)IgM depletion) but this appears very preliminary.

For example

1) That (n)IgM-FN regulates fibronectin is still a hypothesis
2) That (n)IgM-FN is in fact a natural IgM is still a guess
3) What causes (n)IgM depletion is still unknown
4) Why FN is not integrating into immune complexes is still unknown
5) Consequences of #4 above are still unknown
6) Whether IgM infusions will fix fibronectin and immune complex issues is still unknown

Overall his initial statement that a drug already exists and is being tried in ME/CFS and works "beautifully" now seems like an overstatement.

 

[Vlad83]

But that said, I actually would not mind trying IgM infusion, especially since it already exists. However I would think (n)IgM level would need to be checked fist, and such a test is not yet available as far as I can tell.

 

[Osaca]

Now it sounds like they "may" have found something very important (high fibronectin and (n)IgM depletion) but this appears very preliminary.

I can understand why some people will feel disappointed. I think a very neutral listener will probably feel like he overpromised. However, anything he would have presented would have always just been a hypothesis. The deciding question is whether he has the data to back up his hypothesis and whether it can be replicated. Then things can be taken further from there. Progress from there onwards might then be very quick or very slow and still take centuries. One never knows.

ME/CFS most likely won't be solved overnight. We don't know what causes the disease, we don't understand a single of its mechanisms properly, we don't even have a single meaningful measurement. Prusty's hypothesis can be a start to explaining a lot of these things, or also not, but it is unlikely for any theory to hit the nail on the head the first try, given our complete lack of knowledge of the disease.

For me the question shouldn't be whether he solved the disease, but rather whether he provided a stepping stone to solve it.

 

[Osaca]

After listening to Dr. Prusty's interview I really cannot understand why we are not as the whole ME/CFS community persuing clinical trials with anti-purinergic therapy.

One of the reasons on my behalf to not yet advocate for clinical trials with anti-purinergic therapy is because Prusty and Phair/Davis haven’t released any data yet or more to say things are still being finalised. For me that is the fundament to advocate for any trial. It’s hard for me to advocate for something based on an acquired murine model of autism on the basis of no data. Other than that I adore all the efforts you’re putting into this and I know you have extensively looked into it. I hope once the data becomes available a thorough discussion will be had. Perhaps it’s possible to reach out to Naviaux to ask him why he doesn’t seem to believe that anti-purinergic therapy would be too relevant for ME/CFS?

Regarding the the IFNa shunt, does anybody know if new measurements were presented in Cambridge and how the JAK-STAT trials are going? The only data I’ve seen were the plasma IFNa concentrations Phair presented in the videos half a year ago (I only read “IFNa in ME is four times higher than healthy controls” but don’t know much more about these measurements).

 

[serg1942]

One of the reasons on my behalf to not yet advocate for clinical trials with anti-purinergic therapy is because Prusty and Phair/Davis haven’t released any data yet or more to say things are still being finalised. For me that is the fundament to advocate for any trial. It’s hard for me to advocate for something based on an acquired murine model of autism on the basis of no data. Other than that I adore all the efforts you’re putting into this and I know you have extensively looked into it. I hope once the data becomes available a thorough discussion will be had. Perhaps it’s possible to reach out to Naviaux to ask him why he doesn’t seem to believe that anti-purinergic therapy would be too relevant for ME/CFS?

Regarding the the IFNa shunt, does anybody know if new measurements were presented in Cambridge and how the JAK-STAT trials are going? The only data I’ve seen were the plasma IFNa concentrations Phair presented in the videos half a year ago (I only read “IFNa in ME is four times higher than healthy controls” but don’t know much more about these measurements).

Thank you for your answer!

Well, autistic children taking just one dose of suramin in one study, showed significant improvements, and autistic children taking suramin for 3 months in a second study, showed over 50% of overall improvement. Also, the kids from the first study did replicate most of the metabolites normalization previously seen in mice. This is huge in my opinion, specially when anti-purinergic therapy has demonstrated in different studies to correct many of the abnormalities demonstrated to occur in ME/CFS until now.

Also, I've been 2 decades reading papers and I don't think I have ever read an almost complete cure of any chronically ill murine model. And seen that the autistic mice gets practically cured at a metabolic, immunological and biochemistry level, this indicates in my opinion that this pathophysiological mechanism seems to be central. And remember that all metabolic alterations observed in autism are practically identical in ME/CFS.

Why do you say that Naviaux thinks that this pathway is not relevant to ME/CFS? He actually published recently a very thorough paper where he goes in detail on how the purinergic pathway is key in ME/CFS:

https://www.sciencedirect.com/science/article/pii/S1567724923000351?via=ihub

I understand the caution though. I just want to share the result of my research in case it is helpful. I'll love to see the unpublished data!

 

[Osaca]

Thank you for your answer!

No problem at all. I fully understand that you've looked at this topic intensly and probably more intensively than anybody on this forum. Regarding my Naviaux statement: I definitely have to correct that then, as I haven't read his newer study (only a short summary) and made the false conclusion that he would have otherwise insisted more on something that he essentially already knew 30 years ago (which he seems to do in this paper at least, does he suggest an anti-purinergic therapy as well?).

I suppose Naviaux would then indeed be a good person to discuss this with.

 

[bigtiired]

I may be interpreting everything wrong but would a monoclonal antibody lowering fibronectin help, while we search for what could be causing the decrease of IgM fibronectin antibodies?

ChatGpt (take with a grain of salt):
Tocilizumab: Tocilizumab, which targets the interleukin-6 receptor (IL-6R), can indirectly impact fibronectin levels. IL-6 is known to stimulate fibronectin production, and by blocking IL-6 signaling, tocilizumab can potentially reduce fibronectin synthesis.

Secondly, another potential treatment could be IvIG, but for that to work, wouldn't it have to have the IgM fibronectin antibodies? Do any current therapies have this? How would you confirm that say PENTAGLOBIN has the correct IgM antibodies>

I was wondering if anyone had any thoughts on this, or if I am totally off base for thinking lowering IL-6 thus indirectly lowering fibronectin is the wrong way to go about this.

I was wondering if this is how LDN is helping, by lowering IL-6 and then as a consequence lowering fibronectin?

I also saw that LDA might have this same effect too of lowering IL-6. Could this be why these medications help?

Again I am interested in Tocilizumab as it can lower IL-6 in turn lowering fibronectin. There are some good studies on fatigue in RA patients when using Tocilizumab. I can't find much when searching for chronic fatigue patients. Has anyone in the CFS community tried Tocilizumab?

 

[Oliver3]

After listening to Dr. Prusty's interview I really cannot understand why we are not as the whole ME/CFS community persuing clinical trials with anti-purinergic therapy.

On the following post I have compiled a lot of literature indicating that anti-purinergic therapy seems to revert the abnormalities described by Dr Prusty and Dr Phair as part of their HHV-6/Fibronectin1 and itaconate/IFNa etiopathigenic models for ME/CFS, respectively:

https://forums.phoenixrising.me/thr...d-abnormalities-in-me-cfs.90173/#post-2435206

Note that anti-purinergic agents have shown to inhibit fibronectin1 expression, to increase mitofusin-1 expression, to inhibit viral replication/infection (HHV-6, CMV, HIV, HHV1, sars-cov-2,etc.), to inhibit mitochondrial fragmentation, to restore Kreb's cycle abnormalities and antioxidant status (GSH/GSSG, NADH/NAD+), or even to increase total immunoglobulins.

For sure trying to take filgotinib to inhibit the JAK-STAT signal, an IFNa inhibitor, and a TLR-targeted intervention could work, as proposed by Dr Phair. And similarly IVIgG and immunoadsortion therapy seems reasonable, as proposed by Dr. Prusty. But I can't get my head around the fact that nobody is proposing anti-purinergic therapies, after reviewing the literature.

I honestly think that it's akin to the cigarette industry suppressing the smoking data.
I remember there was an antipurigenic treatment being developed by a scientist at Bristol or Southampton university for blood pressure and it was anti purigenic. This was around 2017/8 I think. It just went quiet after he was interviewed talking very confidently about his findings.
Wish I could remember the name of the doc

 

[Sizzle]

Did I just found a connection with the clotting and platelets theory ?