Bhupesh Prusty: "we are on a perfect path for identifying potential transferable factors in ME/CFS blood that can cause mito dysfunction..." GoFundMe

[stefanosstef]

https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.21521

Ilexgenin A inhibits mitochondrial fission and promote Drp1 degradation by Nrf2‐induced PSMB5 in endothelial cells
Previous studies have demonstrated that Ilexgenin A (IA) obtained from Ilex hainanensis Merr. could improve AS development

Ilex hainanensis Merr. is used as a chinese herbal medicine.
Is this available in TCM shops ?

Look for or Shan-Lv or Shan-Lu tea.You can buy it.It's not so easy to be sure it's the same because the Chinese like to keep adding words to their teas so it may have shan lu but contain 5 other words in it and I can't understand if there are different subspecies or it's the same or if they are referring to a mix of herbs.

Edit:I believe this is the correct one
https://caffeinee.com/products/best...nti-aging-qing-shan-lv-shui-full-buds-tee-the

 

[Canned]

It all comes down to get your hands on SS31/Elamipretide or the other one i found recently P110/Mdivi-1. They both show very good and encouraging lab results. We just need them in human Cfs trail as soon as possible now. I was asking Dr. Prusty about Mdivi-1. He already tested it!

Ahh i wish he told us more about the results of the test.. but the fact that he is already testing drugs is Great!

I just read this paper:Paper

SS-31 Peptide Reverses the Mitochondrial Fragmentation Present in Fibroblasts From Patients With DCMA, a Mitochondrial Cardiomyopathy

Isnt the mitochondrial fragmentation exactly what prusty finds to be wrong with our mitos?

 

[MonkeyMan]

Look for, or Shan-Lv or Shan-Lu tea.

Ummm, @stefanosstef, you may want to change that link for Shan-Lv-Cha ... quickly!!

 

[Badpack]

Ummm, @stefanosstef, you may want to change that link for Shan-Lv-Cha ... quickly!!

just some casual porn, what about it haha

 

[Rufous McKinney]

Where are you getting that figure from? There's no way that 2% of the population have real ME, it's fraudulent figures like that which trivialize ME.

Its just some number....like all the numbers....I just read a review paper that used range of numbers...up to 3.78 %.

We continue to be told the vast majority are undiagnosed...and we wait for diagnostics we are told- work.

I'm not trying to trivialize anything.

 

[raghav]

Ilexgenin A has ability to regulate lipid profile and protect the liver against high fat diet (HFD) -induced impairment. 2. Ilexgenin A ameliorates hepatic insulin signaling and gluconeogenesis by regulating lipolysis in white adipose tissue (WAT). 3. Ilexgenin A exerts anti-inflammation and anti-angiogenesis effects through inhibition of STAT3 and PI3K pathways and exhibits synergistic effects with Sorafenib on hepatoma growth. 4. Ilexgenin A has anti-atherosclerotic activity, it shows reduction of atherosclerosis in apolipoprotein E deficient mice. 5. Ilexgenin A inhibits endoplasmic reticulum stress and ameliorates endothelial dysfunction via suppression of TXNIP/NLRP3 inflammasome activation in an AMPK dependent manner, it is useful in the management of cardiovascular diseases in obesity. 6. Ilexgenin A could be regarded as a promising agent for the treatment of melanoma, it exerts anti-melanoma activity by arresting the cell cycle at G0/G1 and regulating IL-6 and TNF-α production.

So it looks like Ilexgenin A is able to get into most tissues. It seems to be doing good all over the body. Does it cross the blood brain barrier ? Anyway we have to see what the optimal dosage is. Because we dont want to completely decimate DRP1. If a molecule is present in the body by nature usually it will be regulated to be within a range. So if we decimate DRP1 100 % then that might not be good. It may cause uncontrolled multiplication of mitochondria. Just my guess. So we have to see what is the safe dosage. I see from literature that it can be taken orally. They have administered it orally in mice.

I will dig up material on the chinese tea. But from what I read from the information posted by @stefanosstef it contains Ilexgenin A (triterpenoids) along with four other constituents. But since it is promoted as an anti aging tea it is worth trying it. Best way is to go to your nearest TCM doctor and tell him /her that you want this tea and how it is to be prepared and the dosage. Should it be taken on an empty stomach and how many times a day. You know the drill. @perrier You may want to pursue this line. Because Ilogenin A is very potent so lets not hurry and try it. The tea seems safer. Its available on ebay also. I think 250 gms costs around 55 usd. So should not be a problem.

 

[sebaaa]

Dear @perrier and @MonkeyMan I am also in a sinking boat so I know what it feels like. Lets make it happen. Lets hound Prusty till he gives in and releases the list of transfer factors and diagnostic tests for the same. I know he is trying to get some mileage out of it. But he is not greedy, that much I am able to say from his emails and tweets. He just wants a way out of HHV-6 research to go into a better paying job (From his tweet where he says Professors in US draw 1-2 million USD per annum whereas the researchers under them who do the actual work get hardly 200k per annum) Lets see how best we can help him in raising his profile. I know after my above tweet he will completely stop replying to my mails. Thats ok. For our collective good I am ready to accept that.

He got an offer to work under a reputed professor in US but the pay was lesser than what he is currently drawing in Germany. He has a wife and kids. So migrating to US on a lesser pay is not worth it even though he will get an elevated status. Lets hope he gets a good enough offer. But we will keep trying to put pressure on him to release the details. In the meantime lets try to raise his profile on social media and hope for the best.

I've also been trying to get something out of him. I've been emailing him to disclose the FDA pre-approved drugs that could apparently treat the unknown "fatigue factors", and also what clinical trials with one of these drugs would cost. I was thinking that maybe I could help with the funding depending on the cost. Get philanthropic associations involved or just philanthropists.

If the phase II and III trials succeed, then you'd make millions and potentially hundreds of millions. Just 2-3 million people in the US alone begging for a cure, and if you'd make 10$ of profit on your drug then that's already a huge ROI. And no marketing budget would really be required since the message of a cure spreads like wildfire just like it did in Norway with the Rituximab trials. I also emailed Dr. Naviaux, but neither one has yet to reply.

 

[MonkeyMan]

Lord knows I'm as desperate for a clinical solution -- i.e., a drug -- as anyone here. 35 years and counting that I've been battling ME/CFS. But I'm a bit concerned by some of the posts here that seem to be implying we should push Dr Prusty about this or about that. Dr Prusty is our ally, and he has been very open, generous, and communicative about his work. So let's not antagonize him or make him feel like he needs to withdraw from communications with desperate patients.

 

[Lisa108]

I'd rather wait and see Dr. Prusty's work being published in a good journal, than have him rush it out now.

 

[Rufous McKinney]

Best way is to go to your nearest TCM doctor and tell him /her that you want this tea and how it is to be prepared and the dosage.

I am conferring with my TCM expert...on whether this is safe for me to take...stay tuned!

Not once: has something I've read about online- been appropriate for me to take. So even this Ilex- there may be other herbs which have a similar result...so I'm curious what my TCM expert will say!

 

[Mary]

I am conferring with my TCM expert...on whether this is safe for me to take...stay tuned!

Not once: has something I've read about online- been appropriate for me to take. So even this Ilex- there may be other herbs which have a similar result...so I'm curious what my TCM expert will say!

Let us know what they say!

 

[stefanosstef]

Sorry fellas!Must have been the autocorrect!

 

[Badpack]

https://diabetes.diabetesjournals.org/content/66/1/193.figures-only

Any diabetic patients here that use Metformin and can tell if they fell better with their fatigue after taking it ?

 

[Badpack]

I bought a handful of kuding tea. Should be here next week. Lets see if a simple tea can heal a now 6y long disease haha

 

[raghav]

https://diabetes.diabetesjournals.org/content/66/1/193.figures-only

Any diabetic patients here that use Metformin and can tell if they fell better with their fatigue after taking it ?

I tried metformin and the first dose itself I crashed. I am diabetic on insulin.

A breakthrough study showed that metformin selectively inhibits complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain and, as a result, decreases NADH oxidation, reduces the proton gradient across the inner mitochondrial membrane, and reduces oxygen consumption rate (El-Mir et al., 2000[7]).

What does this mean ? Does it increase ATP production or reduce it ?

 

[Rufous McKinney]

I googled: your question and perhaps this is more understandable ....

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147388/

Cancer Metab. 2014; 2: 12.
Published online 2014 Aug 28. doi: 10.1186/2049-3002-2-12
PMCID: PMC4147388
PMID: 25184038
Metformin directly acts on mitochondria to alter cellular bioenergetics
Sylvia Andrzejewski,1,2 Simon-Pierre Gravel,1,2 Michael Pollak,3,4,5 and Julie St-Pierre

1,2

Results
We show that metformin decreases mitochondrial respiration, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, cells treated with metformin become energetically inefficient, and display increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle. Conflicting prior studies proposed mitochondrial complex I or various cytosolic targets for metformin action, but we show that the compound limits respiration and citric acid cycle activity in isolated mitochondria, indicating that at least for these effects, the mitochondrion is the primary target. Finally, we demonstrate that cancer cells exposed to metformin display a greater compensatory increase in aerobic glycolysis than nontransformed cells, highlighting their metabolic vulnerability. Prevention of this compensatory metabolic event in cancer cells significantly impairs survival.
Conclusions
Together, these results demonstrate that metformin directly acts on mitochondria to limit respiration and that the sensitivity of cells to metformin is dependent on their ability to cope with energetic stress.

****

Meanwhile...I"m not convinced I can explain this...sounds like LESS mitochondrial activity changes how glucose is used...

glub glub

 

[sebaaa]

Lord knows I'm as desperate for a clinical solution -- i.e., a drug -- as anyone here. 35 years and counting that I've been battling ME/CFS. But I'm a bit concerned by some of the posts here that seem to be implying we should push Dr Prusty about this or about that. Dr Prusty is our ally, and he has been very open, generous, and communicative about his work. So let's not antagonize him or make him feel like he needs to withdraw from communications with desperate patients.

I 100% agree. I just really hope that something useful comes out of this, and that maybe there would be some regular updates or a deadline on when we should expect results, especially now that Covid-19 is affecting research.

I asked him exactly that and from then on he stopped replying to my mails.

He responded to my inquiry about FDA pre-approved drugs. It's not really anything that we don't know. He said "We are testing many potential drugs including Copaxone, Suramin, Mdivi-1 [in vitro]."

From what I understand is that people had already tried Suramin for CFS/ME. It was in another thread. Also, I'm sure p110, Dynasore, and Ilexgenin A also fit into that list since they also inhibit mitochondrial fission like Mdivi-1. At least according to the research. So hopefully he also tries those out.

 

[MonkeyMan]

He responded to my inquiry about FDA pre-approved drugs. It's not really anything that we don't know. He said "We are testing many potential drugs including Copaxone, Suramin, Mdivi-1 [in vitro]."

From what I understand is that people had already tried Suramin for CFS/ME. It was in another thread. Also, I'm sure p110, Dynasore, and Ilexgenin A also fit into that list since they also inhibit mitochondrial fission like Mdivi-1. At least according to the research. So hopefully he also tries those out.

And elamipretide too! That's 7 different agents that inhibit mitochondrial fission! I believe at least two of these have been tested and shown to inhibit impedance in the nanoneedle. If these were all shown to inhibit impedance, wouldn't that be almost proof that Dr Prusty has identified what the problem is?

@Janet Dafoe (Rose49), @Ben H - Is Ron aware of these agents and planning to test them using the nanoneedle?

 

[Badpack]

@MonkeyMan would be really sweet to know what Ron is up to right now and if the new machine is up and running. He talked about it for months now that its just an engineering problem and cheap to make, but he never gave an update. Is Janet answering here at all ? Oct 9, 2018 I wrote a PM to Janet and she never answered.

If more of those agents really normalise the impedance it could really be big. Ofc the next question is who is responsible for the fission. But in the mean time we could treat the symptoms and try to live a normal life again till the rests is figured out.

 

[Badpack]

I watched Dr. Prustys old speech again from the NIH ME research conference in April 2019. There he states that Drp1 isnt responsible for the mitochondrial fragmentation. This would mean inhibiting it with Ilexgenin A and mdivi-1 shouldnt work or help us. In the latest speech he doesnt pick it up again. So that leaves only SS31/Elamipretide. Because it stabilises the mitochondria without the need of Drp1. Another reason to finally get my hands on it.