Health rising blog post, by Cort Johnson, 8 September: Molecular Underpinnings of ME/CFS Explored at the Open Medicine Foundation Symposium

“This is not a disease that can be solved by one person. It needs a community, and lots of expertise. I will work with anybody to do this.” Ron Davis

…It’s always humbling being in the presence of researchers talking about their research. The vast majority of conversation went right over my head.

The Working Sessions and the Symposium

“It takes a village to solve a disease and you’ve created a really great village.” Bob Naviaux to Janet Dafoe during the Working Group sessions.

Ron Davis
Ron Davis started off the session in typical Ron Davis fashion stating that because we really don’t know where to look, we’re looking in as many places as we can.

Davis is very focused on cellular energy production, but is keeping his options open. He’s apparently seen too many sure things go by the wayside to do anything but that. The first step is to look everywhere.

Davis went over the “nano-needle” his lab has produced and its finding of increased cell impedance when ME/CFS cells are put under stress. Those high impedance levels suggest that ME/CFS patients’ cells are unable to meet their energy demands when put under stress.

Perhaps the most striking clue Davis has uncovered thus far is the ability of plasma from ME/CFS patients to make healthy controls’ cells look like ME/CFS cells when stressed, and the ability of plasma from healthy controls to rejuvenate ME/CFS patients’ cells. Davis has found that pyruvate, a substance which bypasses glycolysis, and ATP – a signaling molecule (outside the cell) – makes ME/CFS patients cells look healthy again. (Warning: loading up your body with pyruvate and/or ATP could make you very, very sick.)

Davis has began filtering substances out of ME/CFS patients’ plasma in an attempt to isolate the offending factor. (Note that the problem could also be a missing factor – something missing in ME/CFS patients’ blood.) The first stab indicated that the substance or compound was likely a large molecule; the next that it may be an antibody or something attached to an antibody. That’s an intriguing finding given Mark Davis’ belief that ME/CFS is probably an autoimmune disease.

Severe Patient Big Data Project Findings
Thus far the massive project has identified 14 genes that are possibly implicated in ME/CFS, including one highly suspect gene that had damaging mutations in every severe patient but not in a single healthy control.

Davis, as usual, expressed caution; that gene – which affects serotonin processing and regulatory T-cells – could be associated with severity but may not be causing ME/CFS; i.e. ME/CFS might simply be worse in people with these mutations. Either way, if the finding holds up, it’s a clue – an arrow pointing at an area of dysfunction.

Problems with that gene could conceivably make it difficult to halt the proliferation of T-cells – ultimately putting ME/CFS patients at risk for an autoimmune disease.

Davis also clicked through a number of dead ends: cell free DNA, viruses, new pathogens, mitochondrial DNA concentrations – all of these have been normal in the severe ME/CFS patients. Some of the tests Davis included in the Severe Patient Big Data study he thought unlikely to find answers. So why include them? Because Davis is doing his due diligence – he’s searching everywhere and he’s not rejecting anything without getting data on it.

OMIC’s studies like the Severe Patient Big Data study and the Snyder study (see below) are big, expensive, complex projects but Davis said the genome project and others have shown that they’re actually quite cost-effective. (Certainly more cost-effective than a series of smaller, poorly integrated studies that sniff around the edges of a disease).

Davis’ Working Group talk sparked a lot of interest. Chris Armstrong asked if those stressed ME/CFS cells happened to be swelling. Davis didn’t know but emphasized that they did not appear to be dying. Bob Naviaux suggested adding glucose and using a glucometer to assess glucose levels in the plasma.

The nano-needle test is fast and cheap, but much more work is needed before it can be considered a diagnostic test for chronic fatigue syndrome (ME/CFS).

Read more from the Symposium

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