Merged thread
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From the desk of Ronald W. Davis, PhD
Chair of OMF Scientific Advisory Board
ME/CFS Working Group at Stanford Meeting September 8-10, 2021
Summary by Ronald W. Davis, PhD, and Janet L Dafoe, PhD
This was a great meeting and showed a lot of activity and progress in
ME/CFS research in an ever-growing number of groups. Researchers
presented unpublished and often preliminary results. This style of
scientific meeting can greatly accelerate research because scientists
learn new information much earlier. It can often take a year or more
to get a research paper published. Because of the preliminary nature
of the results, it is essential that they remain confidential and not
made public. Therefore, this is a summary without too many details.
The speakers are listed at the end.
There is continued search for a pathogen(s) that can sustain ME/CFS.
Most studies look for DNA or RNA from a pathogen. In addition, EBV and
HHV6 have gained renewed interest for researchers due to evidence of
activation of these viruses in the absence of DNA replication and
amplification.
There were a number of talks about the metabolomics of ME/CFS. This
work is moving from finding lists of metabolites involved in the
disease to investigating various metabolic pathways. A major focus is
on the nitrogen and BH4 pathways. There is a new focus on pathways in
the mitochondria. This is difficult to study because of the small
amount of mitochondrial metabolites in blood samples. However, this
focus may be at the heart of what=E2=80=99s wrong in ME/CFS.
There was new work presented regarding autoantibodies and immune
dysregulation. It is believed this dysregulation is what is causing
autoantibodies to be present. The next question is, =E2=80=9CWhat is causin=
g
the immune dysregulation?=E2=80=9D There was also new work on
neuro-inflammation, which also might result from the immune
dysregulation.
There was a preliminary report of the molecular changes occurring with
PEM. This will be a major endeavor.
A major effort was reported of an extensive genetic analysis from
published and unpublished DNA sequence data looking for single genes
and combinations of genes and any correlations with phenotypes. This
is the first attempt to put together these previously disparate groups
of data, and it was exciting to see. Thus far, the results are
preliminary, but this is a very important investigation.
We heard an update on red cell deformability. In previous work, some
labs have found a difference in red cell deformability between
patients and healthy controls, and one lab found no difference.
However, it was recently discovered that oxygen levels in the blood
have a major impact on deformability. New instruments are being
developed to measure deformability under controlled oxygen levels.
There is a clear difference in deformability between patients and
healthy controls under low blood oxygen levels. Thus, this continues
to provide promise for a fast and inexpensive biomarker and diagnostic
test.
New results on metabolic traps were presented. It is possible that
there are many different metabolic traps and that these traps may be
the cause of a number of chronic diseases. The tryptophan to
kynurenine trap has been the first to be explored as an underlying
cause of ME/CFS. This trap was first demonstrated in a test tube using
purified enzymes, but does it exist in vivo in isolated cells? Yes! It
was demonstrated that yeast with the Human IDO1 gene inserted into it
became trapped when tryptophan was increased in the medium. Work is
now progressing to determine if human cells can be trapped. Using the
yeast system, screening is proceeding for an FDA approved drug that
will reactivate the Human IDO1 enzyme and get the cell out of the
trap. In addition, a new trap or energy bypass in mitochondria was
presented that could explain the low energy in patients and PEM.
In between the presentations, there was a significant amount of time
for questions, discussions, brainstorming and the forming of
collaborations. It felt like the research on ME/CFS has reached a new
level, and it engendered an ever growing spirit of hope for eventual
treatments and a cure.
Participants:
Christopher Armstrong, Rahaf Assil, Lucinda Bateman, Jonas Bergquist,
Joseph Breen, Lily Chu,Jane Collins, Laurel Crosby, Janet Dafoe, Mark
Davis, Ron Davis, Kenny de Meirleir, Mary Dimmock, Donna Felsenstein,
Jennifer Frankovich, Keith Geraghty, Arnaud Germain, Anna Gil, Ludovic
Giloteaux, Eric Gordon, Michael Gresser, Andrew Crimson, Paul Guyre,
Rebecca Hamlin, Maureen Hanson, Ashley Haugen, Craig Heller, Katrina
Hong, Mady Hornig, Li-Yuan Hung, Fereshteh Jahaniani, Michael Jensen,
Sharada Kalanidhi, David Kaufman, Betsy Keller, Ryan Kellog, Vinod
Khosla, Seoyeon Kim, Nancy Klimas, Kevin Kramer, Crystal Lantz, Joshua
Leisk, Susan Levine, Alan Light, Kathleen Light, Ami Mac, Jessica
Maya, Roya Mazrouei, Neil McGregor, Alain Moreau, Karl Morten, Adam
O=E2=80=99Neal, Anna Okumu, Robert Phair, Bhupesh Prusty, Anand
Ramasubramanian, Amit Saha, Carmen Scheibenbogen, Liisa Selin, Jaime
Seltzer, Amrit Shahzad, Peidong Shen, Richard Simpson, Michael Snyder,
Rivka Solomon, Franziska Sotzny, Linda Tannenbaum, Ronald Tompkins,
David Tuller, Marielle van Kooten, Vanessa Velasco, Jiandi Wan, John
Whiting, Vicky Whittemore, Julie Whilhelmy, Wenzhong Xiao, Sitong Zhou
We are all extremely grateful to all the funders of this research,
including NIH, OMF, Vinod Khosla, international funders, and the
awesome generosity of patients and their loved ones. As usual, the
progress of this research is always slower than it potentially could
be due to limited funds. Donations are so deeply appreciated!
And don't forget: Donations received from now until November 30, 2021
will be TRIPLE matched up to $600,000. So if you donate $10, you
really donate $30!
Donate Now
https://www.omf.ngo/?form=3DTripleTuesday2021
More ways to donate
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from tom kindlon, public