Salugenesis and the Cell Danger Response: Dr. Robert Naviaux

[Mohawk1995]

I have been in the medical field for 30+ years as a Physical Therapist and although I am quite familiar with the "healing process", I have not yet heard this term and how it relates to Chronic Disease states such as ME/CFS. His thinking centers on two things:

• That Chronic Disease states need to be looked at different. Specifically more as an inability of the body to return back through each of the 3 healing stages (Salugenesis). More specifically that it gets stuck in the process at one stage or the other. Usually the Beginning Phase or Middle Phase. And that this correlates with "3 development forms of Mitochondria that undergo programmed interconversion when a cell is injured or stressed".
• As a result, to continue to treat a Chronic Disease State with Acute Disease based treatments is counterproductive (sound familiar for those who suffer with ME/CFS). He advocates a seperate "Book of Medicine" specifically aimed at Chronic Disease States and specifically as they relate to the Cell Danger Response and it's impact on Salugenesis.

This would align with the thinking which places emphasis on ME/CFS being a "protective response gone wrong" and the ramifications of Mitochondrial dysregulation. Namely a lack of focused energy to facilitate the Salugenesis process and disrupt all cycles and systems that depend on energy (ie everything!).

Here is a graphic from his lecture:

Dr Robert Naviaux, "Metabolic Features of Chronic Fatigue Syndrome", NIH ME Conference in April 2019

Here is Youtube link to this talk:

 

[Davsey27]

Good post I think the CDR may be a very solid and plausible explanation in many cases

 

[Pyrrhus]

It's so great when scientists with no personal relation to ME, like Bob Naviaux, take an interest in ME.

We need more people like him looking at ME from a new perspective.

Just a heads-up though: Naviaux's "Cell Danger Response" theory is not accepted by the rest of the immunology community. Some people don't even consider it to be coherent enough to constitute a testable theory...

 

[Mohawk1995]

Just a heads-up though: Naviaux's "Cell Danger Response" theory is not accepted by the rest of the immunology community. Some people don't even consider it to be coherent enough to constitute a testable theory...

I have worked in Healthcare for over 30 years and I really don't put a lot of stock into what the rest of the Medical Community thinks about a certain theory. We in medicine have gotten it wrong so many times especially in the world of chronic diseases and chronic pain. I get that we want Double Blinded Randomized Control studies to support everything we do, but in reality that is not really practicing "Evidence Based Medicine". I think I will start another thread about that topic alone because it is not being correctly practiced according to the original definition of EBM.

 

[Pyrrhus]

I get that we want Double Blinded Randomized Control studies to support everything we do, but in reality that is not really practicing "Evidence Based Medicine"

As a devout Bayesian, I say Amen to that!

 

[leokitten]

Just a heads-up though: Naviaux's "Cell Danger Response" theory is not accepted by the rest of the immunology community. Some people don't even consider it to be coherent enough to constitute a testable theory...

To me this is the big gotcha with CDR. It surprised me when doing a literature search that no one is publishing on it other than Naviaux. And if his theory is correct it’s part of our basic cellular physiology so I wonder why have no other researchers in the entire world described or seen this?

I could be totally wrong, but usually theories about fundamental cellular function as commonplace as this don’t spring out of thin air from one lonely physician.

Well I should mention though that the Prusty HHV-6 2020 paper with Naviaux did cell line experiments and found mitochondrial and other cellular changes which they say is part of the CDR when they exposed cells to CFS serum with supposed HHV-6 proteins.

 

[leokitten]

I have worked in Healthcare for over 30 years and I really don't put a lot of stock into what the rest of the Medical Community thinks about a certain theory. We in medicine have gotten it wrong so many times especially in the world of chronic diseases and chronic pain. I get that we want Double Blinded Randomized Control studies to support everything we do, but in reality that is not really practicing "Evidence Based Medicine". I think I will start another thread about that topic alone because it is not being correctly practiced according to the original definition of EBM.

The problem to me is not the medical community, medicine, physicians, and medical scientists generally aren’t doing cellular biology. What concerns me more is the entire molecular and cellular biology community not already discovering the CDR. Bench science should’ve discovered this.

 

[Pyrrhus]

To me this is the big gotcha with CDR. It surprised me when doing a literature search that no one is publishing on it other than Naviaux. And if his theory is correct it’s part of our basic cellular physiology so I wonder why have no other researchers in the entire world described or seen this?

My understanding is that the immunology community already recognizes intracellular immune defenses to be a de facto third branch of immunology. Whereas older immunology textbooks only discussed the cellular branch of the immune system (innate or adaptive immune cells) as well as the extracellular branch (innate or adaptive humoral components), the intracellular branch of the immune system (PAMPs, DAMPs, TLRs, etc.) is still relatively new.

As far as I can tell, "Cell Danger Response" theory may be just a mitochondria-centric rephrasing of this recognized de facto intracellular branch of the immune system. But I may have misinterpreted Naviaux here...

 

[leokitten]

My understanding is that the immunology community already recognizes intracellular immune defenses to be a de facto third branch of immunology. Whereas older immunology textbooks only discussed the cellular branch of the immune system (innate or adaptive immune cells) as well as the extracellular branch (innate or adaptive humoral components), the intracellular branch of the immune system (PAMPs, DAMPs, TLRs, etc.) is still relatively new.

As far as I can tell, "Cell Danger Response" theory may be just a mitochondria-centric rephrasing of this recognized de facto intracellular branch of the immune system. But I may have misinterpreted Naviaux here...

Thanks for the clarification, so this makes more sense and it’s doesn’t seem like as much of a huge leap from current knowledge as I thought.

 

[leokitten]

My understanding is that the immunology community already recognizes intracellular immune defenses to be a de facto third branch of immunology. Whereas older immunology textbooks only discussed the cellular branch of the immune system (innate or adaptive immune cells) as well as the extracellular branch (innate or adaptive humoral components), the intracellular branch of the immune system (PAMPs, DAMPs, TLRs, etc.) is still relatively new.

As far as I can tell, "Cell Danger Response" theory may be just a mitochondria-centric rephrasing of this recognized de facto intracellular branch of the immune system. But I may have misinterpreted Naviaux here...

From my (very cursory) reading, mitochondria are already central figures in the biology of DAMPs in the literature. Still trying to figure out what Naviaux is saying that is so different, maybe the details of the cellular response itself?

 

[Mohawk1995]

I could be totally wrong, but usually theories about fundamental cellular function as commonplace as this don’t spring out of thin air from one lonely physician.

You would think that, but in some ways unless you go looking for something you won't find it. As an example, just 3-4 years ago scientists discovered that there is a lymphatic system in the brain. This is not a cellular phenomenon but a complex system embedded in the meninges. The discovery basically refuted the concept of a blood brain barrier which had been accepted as fact for many years.

So I am confident, that many other scientists have seen the signs of CDR and just did not pursue digging deeper because their minds were not as open to the concept. There is this mistaken idea that scientists are not biased by their own thinking when in fact all are. It is just those that are aware that they are and put measures into place to account for it that are the true objective scientists. There are not many of those.

Here is a link to the Lymph study synopsis:
https://www.nih.gov/news-events/nih...d that our brains,brain and the immune system.

Interestingly, it is very likely that this system plays a key role in ME/CFS and the shut down of energy production from the CDR has a negative impact on clearing the "waste" from the brain. This then resulting in slowing the filtering of Cytokines and perpetuating brain fog.

 

[Mohawk1995]

From my (very cursory) reading, mitochondria are already central figures in the biology of DAMPs in the literature. Still trying to figure out what Naviaux is saying that is so different, maybe the details of the cellular response itself?

I think the difference is that Naviaux is a rare scientist who has a very in depth knowledge of cellular physiology and at the same time is able to see the systemic and functional outcome of the CDR. To someone less complex (me) in thinking or knowledge, it is simple. You shut down energy production/conversion systemically in the body and everything is impacted by it. Everything. If this is the result of a protective response and is sustained, the logical conclusion would be a disease that looks like ME/CFS.

Maybe my thinking is too small?

 

[Mohawk1995]

Medicine as a science is traditionally poor in looking at systemic or multi-system issues because it is so focused on finding THE Diagnosis. Most if not all issues in the body are rarely that isolated. It is typically the case of this AND this AND this..... Doesn't fit the text books and absolutely does not fit reimbursement schemes.

 

[Wishful]

The discovery basically refuted the concept of a blood brain barrier which had been accepted as fact for many years.

Has it? The BBB is still there, protecting our brains from things trying to cross from the blood vessels. The BBB does have mechanisms for opening the proper amount at the proper times to allow waste to travel out. The meningeal lymph network seems like just another plumbing system that the BBB can open to.

BTW, while checking that, I found that the 'new' lymph network is not a new discovery, but rather a rediscovery of an 18th century discovery. That researcher's findings got poo-poo'ed because it went against 'what everyone knew' and also because no one else had the skill to duplicate his experiment (freezing mercury in the network I think).

 

[Mohawk1995]

Has it? The BBB is still there, protecting our brains from things trying to cross from the blood vessels. The BBB does have mechanisms for opening the proper amount at the proper times to allow waste to travel out. The meningeal lymph network seems like just another plumbing system that the BBB can open to.

It refuted the "concept" that the BBB is an exclusive barrier that does not allow for immune responses against antigens originating from the CNS. This does not mean that the mechanism called the Blood Brain Barrier is not a physiological entity. It just suggest that it would be best described as a highly selective "Blood Brain Filter". The thinking that the Brain is "immune priviliged" is the concept that this "discovery" appears to refute.

BTW, while checking that, I found that the 'new' lymph network is not a new discovery, but rather a rediscovery of an 18th century discovery. That researcher's findings got poo-poo'ed because it went against 'what everyone knew' and also because no one else had the skill to duplicate his experiment (freezing mercury in the network I think).

You are correct in that "discovery" of meningeal lymphatic vessels appears to be credited to Paolo Mascagni in 1787. It was not widely accepted most likely because there was not the same context as there is today with the advances in Neuroscience made in the past 20-30 years. Specifically our understanding of Neuro-immune features and Neuro-inflammatory responses. Context is a key element in research that seems to be dismissed very easily by those who think dogmatically.

Interestingly, of the articles I read that refute this being a "recent discovery", 90%+ were written by Italian researchers. Coincidence to Mascagni being Italian? I think not!

 

[Pyrrhus]

I wonder if there might be some confusion here between lymph drainage in the meninges and lymph drainage in the interior of the brain. Lymph drainage in the meninges has been known for a while, but it was not considered a "true" lymphatic system, since the meninges is only on the surface of the brain and does not penetrate the interior of the brain. What might be "new" is the discovery of lymph drainage in the interior of the brain.

It refuted the "concept" that the BBB is an exclusive barrier that does not allow for immune responses against antigens originating from the CNS. This does not mean that the mechanism called the Blood Brain Barrier is not a physiological entity. It just suggest that it would be best described as a highly selective "Blood Brain Filter". The thinking that the Brain is "immune priviliged" is the concept that this "discovery" appears to refute.

I'm afraid I have trouble seeing how the discovery of lymph drainage in the interior of the brain refutes our conception of the blood-brain barrier. The blood-brain-barrier has always been known as a semi-permeable filter that occasionally lets blood-borne immune cells through, although rarely. The reason that the central nervous system is considered "immune-privileged" refers to the fact that the blood-brain-barrier only rarely lets blood-borne immune cells through, while the tissue barriers around other organs in the body are much more permeable to blood-borne immune cells.

 

[Mohawk1995]

I'm afraid I have trouble seeing how the discovery of lymph drainage in the interior of the brain refutes our conception of the blood-brain barrier. The blood-brain-barrier has always been known as a semi-permeable filter that occasionally lets blood-borne immune cells through, although rarely. The reason that the central nervous system is considered "immune-privileged" refers to the fact that the blood-brain-barrier only rarely lets blood-borne immune cells through, while the tissue barriers around other organs in the body are much more permeable to blood-borne immune cells.

You would be surprised at how the Blood Brain Barrier concept has been used in Medicine. You are obviously more astute than most and your clarification on lymph drainage on the interior of the brain being what is "new" is better said than I can. The key point is that many in Medicine have and still believe in an actual complete Blood Brain "Barrier" and the recent research appears to put even more holes in that concept. Well said btw.

 

[Rufous McKinney]

You shut down energy production/conversion systemically in the body and everything is impacted by it. Everything.

I think this is a major point that some seem to miss. We use energy for EVERYTHING. And the body shuts down systems when- its not available. And so we are in this chronic state of- deprivation.

The notion that our lymph system was not in our brains...seems pretty ridiculous. We also potentially have another system- a type of vascular system thats connective tissue and sends signals...that acupuncture speaks to.

 

[leokitten]

I think it just refuted the concept that the brain was an immune privileged area like inside your eye or in men the testes. No only did they discover the drainage areas it is understood now that T cells do cross over the BBB when signaled that they are needed.

 

[Mohawk1995]

I think this is a major point that some seem to miss. We use energy for EVERYTHING. And the body shuts down systems when- its not available. And so we are in this chronic state of- deprivation.

Literally the Elephant in the Room! We get caught up in all of the Metabolic, Viral, Stress and Functional features of ME/CFS that it is easy to forget it is all about energy first and protection second. The combination of a dysregulated system that is energy depleted (with minimal capacity if any to rebound) and at the same time in a super vigilant state of protection.