The Naviaux Protocol (Remove the Trigger / Refill the Tank / Flip the Switch)

Jesse2233

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Dr Robert Naviaux has suggested a three phased model for reversing the cell danger response (CDR), and recovering ME/CFS patients from a dauer hypometabolic state. I haven't seen it discussed on a dedicated thread, and I thought it was worth delving into.

Note: This is based on Dr Naviaux's 5/25/17 call with the CDC, his 2016 Hypometabolic study, and his theoretical model for future treatment. He is not a practicing clinician, and it's not an approach he's currently recommending.


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The Naviaux Protocol
  1. Remove the trigger. This would presumably mean treating any underlying pathogen (antivirals, antibiotics), treating autoimmunity or autoinflammation (immunosuppressants), unbinding toxins (metals, mold), or avoiding certain environments (mold, chemicals, etc).

  2. Refill the metabolic tank. Naviaux specifically implicates NAD+, NADPH, Glycerol, and Citrulline as key metabolites that rise when nematodes (C. elegans) exit hypo-metabolism (See slide below). On the CDC call he also mentioned that there are hundreds of others that his research data is identifying.

  3. Flip the switch. Naviaux mentioned that he's raising funds for a low dose trail of a drug called suramin in ME/CFS patients (antipuringeric therapy). Suramin is an IV pharmaceutical used in African sleeping sickness that was shown by Naviaux to reverse autism in mice (1a) and more recently in human children (1b).

    I've seen no mention anywhere online of any ME/CFS patient ever trying suramin. Note that it has quite a nasty side effect profile, which is presumably why Naviaux plans to test in low doses.

    Interestingly suramin has also been looked at for treating RNA viruses (2) and cancer (3).
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In practice this protocol might look something like:
  1. Rituximab / Rega Compound 17 (4)

  2. Various supplements

  3. Suramin
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More on suramin from Naviaux's autism study:

Suramin is an APT mediator that triggers the mechanism linked to mitochondria, influences immunity, and has the ability to stabilize locomotor function and coordination, social behavior, normalize brain synapse structure, cell-to-cell signaling, and recover mitochondrial metabolism in mice with autistic-like behaviors and genetics.
And from Wikipedia:

Suramin is also used as a research reagent to inhibit the activation of heterotrimeric G proteins in a variety of GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin, the A1 adenosine receptor, the D2 receptor,[17] the P2 receptor,[18][19] and ryanodine receptors.[20]
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Ref: Slides from Naviaux's CDC call

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Sushi

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Remove the CDR trigger if it's still present. This would presumably mean treating any underlying pathogen (antivirals, antibiotics), unbinding toxins (metals, mold), or avoiding certain environments (mold, chemicals, etc).
Or, it could be an immune trigger to a pathogen that is no longer active, but the immune system is still reacting as if it were.
 

Nickster

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Dr Robert Naviaux has suggested a three phased model for reversing the cell danger response (CDR), and recovering ME/CFS patients from a dauer hypometabolic state. I haven't seen it discussed on a dedicated thread, and I thought it was worth delving into.

Note: This is based on Dr Naviaux's 5/25/17 call with the CDC, his 2016 Hypometabolic study, and his theoretical model for future treatment. He is not a practicing clinician, and it's not an approach he's currently recommending.


--------------

The Naviaux Protocol
  1. Remove the trigger. This would presumably mean treating any underlying pathogen (antivirals, antibiotics), treating autoimmunity or autoinflammation (immunosuppressants), unbinding toxins (metals, mold), or avoiding certain environments (mold, chemicals, etc).

  2. Refill the metabolic tank. Naviaux specifically implicates NAD+, NADPH, Glycerol, and Citrulline as key metabolites that rise when nematodes (C. elegans) exit hypo-metabolism (See slide below). On the CDC call he also mentioned that there are hundreds of others that his research data is identifying.

  3. Flip the switch. Naviaux mentioned that he's raising funds for a low dose trail of a drug called suramin in ME/CFS patients (antipuringeric therapy). Suramin is an IV pharmaceutical used in African sleeping sickness that was shown by Naviaux to reverse autism in mice (1).

    I've seen no mention anywhere online of any ME/CFS patient ever trying suramin. Note that it has quite a nasty side effect profile, which is presumably why Naviaux plans to test in low doses.

    Interestingly suramin has also been looked at for treating RNA viruses (2) and cancer (3).
--------------

In practice this might look something like:
  1. Rituximab / Rega Compound 17 (4)

  2. Various supplements

  3. Suramin
--------------

More on suramin from Naviaux's autism study:



And from Wikipedia:



--------------

Ref: Slides from Naviaux's CDC call

View attachment 21401
View attachment 21402
Thank you for the breakdown. Looking at this it seems very plausible and could work. How does this process get moved forward? Sorry, I try not to be impatient.
 

Alvin2

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I don't think we know enough to be tinkering with things we don't understand.
It could make the problem much worse, not that its not terrible already.
 
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I wonder what would happen if one flipped the switch without removing the trigger
If the original event(s) that started ME, is no longer an active threat, then there is no need to be concerned.
The techniques of how to actually establish "The Who, What, When, Where, Why" of the trigger(s) may take a long time.
So I would assume, for now, the best thing to do is to "refuel" and "flip the switch".
 

Alvin2

The good news is patients don't die the bad news..
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If the original event(s) that started ME, is no longer an active threat, then there is no need to be concerned.
The techniques of how to actually establish "The Who, What, When, Where, Why" of the trigger(s) may take a long time.
So I would assume, for now, the best thing to do is to "refuel" and "flip the switch".
I would want to know why ME/CFS is happening before playing with it, if its a legitimate protection mechanism that is protecting us from something that we currently have then shutting it off could kill us.
 
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I don't think we know enough to be tinkering with things we don't understand.
It could make the problem much worse, not that its not terrible already.
Yes, this is very true. This may be the case for some already? You would need to find a qualified doctor with many years of experience to take you on the journey.
 

CFS_for_19_years

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I wonder what would happen if one flipped the switch without removing the trigger
After a brief time of greatly improved health, there might be a relapse. I'm basing this on the fact that several of us here have posted about spontaneous 100% remissions, only to then go back to the previous level of functioning. My reversal back to health came after an acupuncture treatment, and I was totally well for a few days, only to slip back to my usual sick self :(
 

Alvin2

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Yes, this is very true. This may be the case for some already? You would need to find a qualified doctor with many years of experience to take you on the journey.
I think we need to understand how this starts, what it is and how the treatment works, because if they are correct and its a physiological response then we should not blindly play with it.
For example if its caused by a protein secreted by an intestinal microbiome imbalance then a fix may involve killing the offending bacteria and if not enough taking a reset pill. Then again if its an immune malfunction playing with it could lead to a fatal autoimmunity reaction
That said some people do spontaneously recover and some go through periods of recovery and relapse, so this does give us hope that treatment is possible (though it may also mean that it is an active protection mechanism which could be good news, shut off the cause, trigger turns itself off), but i prefer to play with data rather then fire.
 

halcyon

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The Naviaux Protocol
  1. Remove the trigger. This would presumably mean treating any underlying pathogen (antivirals, antibiotics), treating autoimmunity or autoinflammation (immunosuppressants), unbinding toxins (metals, mold), or avoiding certain environments (mold, chemicals, etc).

  2. Refill the metabolic tank. Naviaux specifically implicates NAD+, NADPH, Glycerol, and Citrulline as key metabolites that rise when nematodes (C. elegans) exit hypo-metabolism (See slide below). On the CDC call he also mentioned that there are hundreds of others that his research data is identifying.

  3. Flip the switch. Naviaux mentioned that he's raising funds for a low dose trail of a drug called suramin in ME/CFS patients (antipuringeric therapy). Suramin is an IV pharmaceutical used in African sleeping sickness that was shown by Naviaux to reverse autism in mice (1).
Looking at the patients who have recovered on drugs used in controlled trials, steps 2 and 3 don't seem to be necessary. Some recover completely on rituximab, ampligen, or interferon alpha. You might argue that the people that don't recover require step 2 and 3, but I doubt that. I think that the ones that fail on these treatments fail on step 1 alone.
 
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I wonder what would happen if one flipped the switch without removing the trigger
If you flip it with Suramin, you get a transient effect, apparently. In the autism study, all the kids go back to more or less how they were after six weeks, as the suramin is eliminated from their body and falls below a certain low threshold

Naviaux mentions this in the study limitations section:

Parents reported that the rate of new behavioral and developmental improvements continued to increase for the first 3 weeks after the single dose of suramin, as blood levels of suramin fell from 12 to 4 μmol/L, then gradually decreased toward baseline over the next 3 weeks, as blood levels fell further from 4 to 1.5 μmol/L. This pattern of response suggested a threshold effect at about 4 μmol/L that could not have been predicted on the basis of what was known about suramin before this study, and outcomes were not measured at 3 weeks.

In circumstances where suramin was toxic, it was kept at levels many magntiudes higher than that threshold for extended periods

The side-effect profile of high-dose suramin (150–270 μmol/L) is known from cancer chemotherapy studies.[32] The side-effect profile from medium-dose suramin (50–100 μmol/L) is known from African sleeping sickness studies.
 
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My use of whey protein (alongside all my usual supps and also d-ribose) has had a profound effect on me.

It might count as refilling the tank under this way of looking at things.

As for triggers, I think there are three levels, all nested within each other. The initial insult; things that make your symptoms worse (e.g. certain environments, chemicals, foods); and of course, exercise itself. Removing the initial insult is not possible (assuming it is not a chronic infection) but removing the other things might be.
 

Jesse2233

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If you flip it with Suramin, you get a transient effect, apparently. In the autism study, all the kids go back to more or less how they were after six weeks, as the suramin is eliminated from their body and falls below a certain low threshold

Naviaux mentions this in the study limitations section:

Parents reported that the rate of new behavioral and developmental improvements continued to increase for the first 3 weeks after the single dose of suramin, as blood levels of suramin fell from 12 to 4 μmol/L, then gradually decreased toward baseline over the next 3 weeks, as blood levels fell further from 4 to 1.5 μmol/L. This pattern of response suggested a threshold effect at about 4 μmol/L that could not have been predicted on the basis of what was known about suramin before this study, and outcomes were not measured at 3 weeks.

In circumstances where suramin was toxic, it was kept at levels many magntiudes higher than that threshold for extended periods

The side-effect profile of high-dose suramin (150–270 μmol/L) is known from cancer chemotherapy studies.[32] The side-effect profile from medium-dose suramin (50–100 μmol/L) is known from African sleeping sickness studies.
Yes, in that case it may be necessary to take low dose suramin long term