Thread by @tessfalor

#IIMEC15 Ron Davis

He's wearing all black, because it's the "uniform of #MECFS". @DafoeWhitney doesn't do well with color, so he's used to wearing black

How do you determine the molecular cause of #MECFS & #LongCOVID?

and how do you treat it?

What happens just before start of #MECFS?

1. viral
2. bacterial or parasite
3. auto accident
4. childbirth
5. vaccination
6. surgery

He thinks innate immunity is the problem and what we should be looking at.

Those initiators also can cause major changes in the microbiome.

Can an altered microbiome cause #MECFS?

When Whitney couldn't eat anymore. Started TPN, conducted metabolic analysis that showed NO metabolites produced by microbiome. There was no change in #MECFS symptoms. After 1.5 yrs installed J tube to feed gut, metabolites changed, no change in symptoms

"The microbiome could cause some symptoms for some patients, but I don't think it causes #MECFS"

Do patients have MS or #MECFS?

Myelin Basic Protein (MBP) digest by catalytic antibiotics from ME and HC

It appears that about 25% of patients have both

@chydorina

Low Dose Abilify

Study by Laurel Crosby - 75% responders, but not double blind. 3 grant applications in now to do double-blind

LDA is thought to increase dopamine

BH4 is required for several metabolic enzymes

Both serotonin and dopamine require BH4

Another reaction might be even more important - arginine to citrulline and generates NO

They will be looking more at BH4. Have to stabilize within 5 minutes.

Patients are usually low in iron, manganese, and copper. Those metals get in cells via transporter DMT1, which doesn't work without NO (that requires BH4)

Genetics
mutations found that can make symptoms worse (not in coding regions)

Search for a pathogen associated with #MECFS
didn't find any new or known pathogens, was very sensitive search for known DNA viruses (same as HC), very sensitive search for parasite - didn't find, very sensitive search for known RNA viruses - developed new methods

20 DNA virus panel - 82% of COVID patients in ICU have an activated virus, mostly EBV

Metabolic trap

when tryptophan gets too high, limits IDO1, can't make kynurenine (substrate inhibition)

The have found several FDA approved drugs that reverse the trap.

Looking at concentration, trying to figure out how to safely give patients those drugs

Low iron can amplify the trap

ATP production

upon infection, IFN alpha is produced and initiates the itaconate pathway in most every cell

itaconate pathway is in mitochondria and decreases ATP production

"I'm optimistic...we're posed for a breakthrough. I think this disease is curable."

"I've talked to patients who have spontaneously gotten over it after being sick for years"