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OMF: New Metabolomics Study Begins (Davis, Naviaux)

mango

Senior Member
Messages
905
Now that the ME/CFS Severely Ill-BIG DATA Study is fully underway, we want to perform multiple investigations at the same time. Because of the many recent small and large donations, we can start another research project now without waiting.

We are very excited to announce an amazing new collaboration with Dr. Robert Naviaux and our very own Dr. Ronald Davis, director of our ME/CFS Scientific Advisory Board. As previously announced, Dr. Naviaux (of the University of California, San Diego, School of Medicine) also joined our Advisory Board and brings remarkable knowledge in metabolomics and mitochrondia.

In addition to Dr. Naviaux and Dr. Davis, the new study is being conducted in collaboration with Dr. Paul Cheney and Dr. Eric Gordon’s team. Dr. Davis will correlate the metabolic findings with genetic results.

What is Metabolomics: Simply put, it’s the study of metabolites, which are chemicals produced as cells carry out their functions. When you know what a body’s cells are producing, you can find out how the cells are functioning, whether normally or abnormally. And if it’s not functioning normally, you can see what aspect of the cells’ activities are defective by measuring the metabolites.

Read the following for more details from Robert K. Naviaux, MD, PhD.: [...]

http://www.openmedicinefoundation.org/2016/05/17/new-metabolomics-study-begins/
 

A.B.

Senior Member
Messages
3,780
Dr. Eric Gordon, his team in Northern California and I recently completed a metabolomics study of over 80 participants, half with ME/CFS and half normal controls. The results showed that there was a chemical signature in ME/CFS that might ultimately be used to help physicians diagnose and treat the disease.

The results were so exciting that we have expanded our pursuit and have launched a validation study in a completely independent group of over 100 participants (already chosen and ready to go), half with ME/CFS and half normal controls from across the US and Canada. A grant from OMF will make this new study possible.

Sounds good. Both the biomarker candidate, and the validation study being launched immediately.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Imagine a treatment that just flips a switch, and boom, you're back to your old fully capable self! OMG!!!

I can barely dream of something like that!

Piece will be on #MEAction tomorrow AM. This is the best news we've had in a long while.

Did you guys see that someone donated nearly half a million dollars to fund this? One. Person. Or entity, but still. Whoever you are, thank you so much.
 
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Sasha

Fine, thank you
Messages
17,863
Location
UK
I really feel like they should give us the first letter of the metabolite so we can have some fun guessing in the meantime.

A...apple!

It says "a chemical signature" so maybe it's more than one?

I've absolutely no idea what I'm talking about, though. :)
 

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
I've read about Naviaux's cell danger response theory before but didn't realise that the mitochondria were so deeply implicated.
Naviaux said:
Mitochondria also have another key function: They stand guard over the cell, ready to defend it when things go wrong. When a virus attacks, or a toxin is detected, mitochondria stop what they were doing, change their shape and cellular locations, and take up arms to help defend the cell. Mitochondria then send messages in the form of metabolites to the nucleus of the cell and to neighboring cells to signal the danger so gene expression can be changed and neighboring cells can prepare for battle. Different signals are sent when the danger has passed to alert the cell that healing can proceed.

Recent scientific discoveries in our lab have shown that several different chronic complex diseases can result when this “cell danger response” (CDR) gets stuck in the “on” position for too long. When the CDR gets stuck, normal healing can’t proceed.  If this happens, it could theoretically lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

See also:
http://www.sciencedirect.com/science/article/pii/S1567724913002390
Abstract
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation.

The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal.

When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results.

Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development.

An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.

[I've broken the abstract into paragraphs]
 
Messages
2,087
I really feel like they should give us the first letter of the metabolite so we can have some fun guessing in the meantime.

A...apple!

Didn't we play that game with the lipkin study - was that related to this in any way ?
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,402
Location
Toronto, Canada
Maybe i am just in denial, but i really believe it's possible. Natural remissions happen all the time, so the human body is capable of recovering from this.

I concur.

I recovered from my first 2 bouts (8 mos and then 2 months) of ME. This third bout has been almost 18 months, but I still believe (most days) that I will recover and get back to my life.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
They stand guard over the cell, ready to defend it when things go wrong. When a virus attacks, or a toxin is detected, mitochondria stop what they were doing, change their shape and cellular locations, and take up arms to help defend the cell.

Whut.

I've never heard that mitochondria were involved in cellular defense in any way, shape or form. I *taught* this, and while I went beyond "powerhouse of the cell" simplicity, I never had any idea that mitos did this.

Anyway, if one goes by the review article @Scarecrow links, Naviaux's premise is that the metabolites that are dysfunctional are 'p' for 'purines'... purine metabolism is wonky. Purines are adenine and guanine -- the adenine that's the 'a' in ATP.

When ATP synthesis, nucleotide metabolism, and associated purinergic signaling are disturbed, a coordinated set of cellular responses is triggered that evolved to help the cell defend itself from microbial attack or physical harm. Elements of this cell danger response (CDR) have been given many names that reflect the level and tools of analysis used to study it. The CDR includes the:
These can be understood as a unified, and functionally coordinated response by considering the CDR in its most fundamental and most ancient role; to improve cell and host survival after viral attack. The acute CDR produces at least 8 functional changes:
  1. it shifts cellular metabolism from net polymer synthesis to monomer synthesis to prevent the hijacking and assembly of cellular resources by intracellular pathogens
  2. it stiffens the membranes of the cell and circumscribes an area of damage to limit pathogen egress
  3. releases antiviral and antimicrobial chemicals into the pericellular environment
  4. increases autophagy and mitochondrial fission to remove intracellular pathogens
  5. changes DNA methylation and histone modification to alter gene expression
  6. mobilizes endogenous retroviruses and other mobile genetic elements like the long interspersed nuclear elements (LINEs) to produce genetic variations
  7. warns neighboring cells and distant effector cells of the danger
  8. alters the behavior of the host to prevent the spread of infection to kin and sleep patterns to facilitate healing (Fig. 1).
Significant shifting of the layout, but no words were altered (maybe I removed an 'and'.)

1-s2.0-S1567724913002390-gr1.jpg

(This is Figure 1.)

I'm tired, but I'm really sick tonight, so, yeah. I had the time to do this. :ill::sleep: <--- latter one is in my imagination.