Open Medicine Foundation (OMF)

We also managed to get a US Defense grant for this project. We're excited about this project, had to set it up as a clinical trial, so a lot more regulations than anticipated but we begin recruiting in Feb 2025.

 

https://www.youtube.com/watch?v=aUl2cSZ9fUg

 

I really enjoy taking notes on videos and summarizing, so here's for the above video:

Main takeaways

• Ron Davis discusses a project at OMF focused on the study of neutrophils in ME/CFS.
• A researcher at OMF named Vanessa is helping design a system for efficient, accurate study of neutrophils (components of the innate immune system), which have not been studied much, as they can not be easily stored.
• They are creating devices and software to automatically track and analyze neutrophils as they move, and collaborating with Michelle James who is able to provide a steady stream of patient samples.
• Some preliminary testing showed that ME/CFS neutrophils move slower than controls, but this needs to be confirmed.
• They hope to be able to analyze many aspects of different blood cells as well.
• Data from this neutrophil project could potentially be used for diagnostics. If they find useful markers, a test could be made very cheaply.

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Discussing Neutrophil Assessment Project, and talking about a researcher at OMF named Vanessa who is leading this project.

Gives some background on neutrophils: These cells are part of the innate immune system. They are found in the blood and tissues, surveying for danger, including bacterial infections. One function is that they can explode near a bacterial infection to trap bacteria in a web of DNA. This is one reason they are difficult to study, since they can be easily activated and made to self-destruct.

Another reason they are difficult to study: Researchers typically store neutrophils by freezing them, but this destroys them. Thus researchers are essentially studying an altered form of the cells, which means they may be missing important clues. Vanessa wanted to find a better method of study.

Vanessa's method involves making the cells move through a filter using chemical attractants, which means only live, functional cells make it through. They worked with a mathematician (Sharda?) to create programs to automatically track these neutrophils as they move, which is much easier than standard, slow manual methods.

They are also collaborating with a researcher named Michelle James, who is able to provide a steady stream of fresh blood samples, which are necessary since neutrophils can't be frozen and stored.

One of the early findings, which they need to confirm, was that ME/CFS neutrophils move slower toward an attractant, which could potentially be useful for diagnostics.

Also collaborating with Jiandi Wan at UC Davis, who is creating a device to measure the impedance of red blood cells, and the time it takes them to cross a channel. This could potentially be a very inexpensive diagnostic tool (around $1 per test). Neutrophils could potentially be tested in the same way.

They basically have everything set up for neutrophil testing, and plan to proceed with data collection. Initially neutrophil study will be very exploratory and all-encompassing in nature, since neutrophils have not been studied much. The hope is for diagnostic markers, but there is a chance of treatment leads.

The limiting factor is mainly getting samples from patients. They try to make sample collection outside the lab possible for patients concerned about infections.

Vanessa is also working on making the device provide more general reports about blood, such as counts of different cells, but done automatically, which in the past has been done manually.

Davis shares his belief about the value of these science updates: Publication of study data can take an extremely long time, and patients "need to know that people are working pretty hard, and there's some really good scientists that are working on this."

 

And yet we see @Jonathan Edwards putting up his paper on Queios for comment and Chris Ponting putting DecodeME preprints up. Are we seeing anything at all from OMF? Wouldn't it be a good idea to put preliminary versions of papers up so that they can get comments and strengthen the papers, and get the info properly out there for other scientists without delay?

 

Main takeaways

• Armstrong's lab thinks there may be links between neuroinflammation, hormone production, and cerebral blood flow in ME/CFS, long COVID, and POTS, so they are measuring all of these in one study. They are looking at astroglia-based neuroinflammation, which has not yet been studied in these populations.
• They are particularly interested in looking for alterations in glumatate or glutamate receptors around the hypothalamus, which may be affecting hormones. They'll also measure hormones outside the brain.
• There will also be a minor exertion component, using a hand grip strength device while doing brain imaging, to see if there are changes in blood hormones or metabolic markers after exertion, and whether cerebral blood flow is affected during or immediately after exertion.

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Danielle Meadows interviews Chris Armstrong about an ongoing study using neuroimaging in long COVID, ME/CFS, and POTS to look at cerebral blood flow and neuroinflammation. Also they want to study involvement of the HPA axis, which includes the hypothalamus that produces a variety of hormones, and these hormones have had some evidence of being dysregulated in ME/CFS and LC. They want to see if altered blood flow or neuroinflammation is affecting the hypothalamus, causing these hormone issues.

They reference an ongoing study on neuroinflammation by Jonas Bergquist. Bergquist's study is looking at microglia neuroinflammation using a marker called TSPO. Conversely, Armstrong's study is looking at a tracer called SMBT-1, which would show inflammation on astroglia (AKA astrocytes). This type of inflammation has never been studied in ME/CFS or LC.

Armstrong is also using MRS (magnetic resonance spectroscopy) to look at levels of neurotransmitters, such as glutamate, around the hypothalamus, which may be causing dysregulation in this region. They will also measure peripheral hormone levels, to see if they relate to these neurotransmitter levels.

Also tracking a tracer of blood to measure blood flow through the brain.

The driving force behind this project is one of Armstrong's PhD students, Ellen (sp?), who has developed a hypothesis about glutamate receptors being altered in the brain, and possibly playing some role in brain dysregulation. Otherwise, they also just want to find links between neuroinflammation, blood flow, and hormones.

Study will also have participants do hand grip exercises while in the scanner to see if there is some alteration in blood flow due to exertion. Also they will look at blood before and after this minor exertion, in case there are any meaningful differences.

Currently awaiting ethics approval, but plan to provide details on enrollment through OMF and StudyME. [So sign up if you want to be notified about enrollment in this or other studies!]

 

Thank you! I struggle a bit with videos (I rarely even watch TV), so to have a summary is a real gift.

 

Thank you, really useful summaries.

 

Announcement from OMF:

The Heart of the Matter

• OMF has received funding to start an ME/CFS biomarker study, called BioQuest.
• The goal of BioQuest is to identify a biomarker for ME/CFS that can be evaluated through a blood test and differentiate it from similar conditions.
• The study team plans to measure over 10,000 proteins and metabolites in blood samples of up to 1,200 patients and controls that have already been collected and stored.
• Additional funding is needed to ensure we can test all collected samples.

BioQuest: An ME/CFS Biomarker Study
We are excited to announce that, thanks to our generous donors, we have successfully secured $800,000—one-third of our goal—that will allow us to initiate a large-scale ME/CFS biomarker study (BioQuest)!

The lack of a diagnostic test for ME/CFS is a widely acknowledged problem for both patients and healthcare providers. Symptom-based diagnosis can not only be subjective, but overlap with other conditions, ultimately delaying diagnosis and clinical management of the disease. Therefore, the goal of BioQuest is to identify a biochemical signature for ME/CFS that can be conveniently evaluated through a blood test and would differentiate ME/CFS from other similar conditions.

Open Medicine Foundation is uniquely poised to conduct this study, with access to up to 1,200 patient and contrast control samples—including multiple sclerosis, fibromyalgia, and autoimmune disorders—that are already collected and stored. In this study, the team will measure over 10,000 proteins and metabolites in these blood samples. Then, using bioinformatic and artificial intelligence techniques, they will try to identify a 5-20 protein/metabolite biomarker that is unique to ME/CFS.

With the initial funding we received, the study team can proceed with finalizing the study design and obtaining the necessary approvals (the first stage of the research process) to begin testing a portion of the already collected samples.

Link

 

Thank you @forestglip. Really helpful.

 

Hopefully this biomarker will indeed be "unique" and hopefully it will not be unique between ME/CFS patients and healthy controls only.

 

From their end of year newsletter:

Coming in 2025: Science Wednesdays

Starting January 1, 2025, OMF will be introducing Science Wednesdays. Every Wednesday (based on United States time zones), tune in to our social media to read a little bit about pieces of science, research, and technology that connect to OMF’s ME/CFS and Long COVID research projects.

 

"Open Medicine Foundation (OMF) is proud to announce the addition of two distinguished experts to our esteemed Scientific Advisory Board (SAB): Dr. Michelle James and Dr. David Kaufman."

Read more here

 

Michelle James is great.

https://med.stanford.edu/profiles/michelle-james

You could search this forum for comments on Kaufman

 

New Publication: Targeted Analysis of Seven Selected Tryptophan-Melatonin Metabolites

The ME/CFS Collaborative Center at Uppsala published a paper on their new methodology: ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), which can separate and quantify tryptophan metabolites with good precision and in under ten minutes.

 

Full Article: Targeted analysis of seven selected tryptophan-melatonin metabolites: Simultaneous quantification of plasma analytes using fast and sensitive UHPLC-MS/MS

Abstract
Tryptophan-derived metabolites, a group of neurotransmitters essential for various brain functions, play key roles in regulating mood, movement, sleep, and cognition. However, the comprehensive characterisation of tryptophan-melatonin pathway metabolites is challenging due to factors such as their structural diversity, chemical complexity, low concentrations, and instability of these metabolites.

In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) methodology with electrospray ionisation for the simultaneous separation and quantification of tryptophan metabolites in human plasma. The analytical calibration ranges in plasma were 0.50–200 ng/mL for serotonin, 0.01–5 ng/mL for N-acetylserotonin, 0.01–20 ng/mL for tryptamine, 0.01–20 ng/mL for 6-sulfatoxymelatonin, 0.01–20 ng/mL for 6-hydroxymelatonin, 0.01–100 ng/mL for melatonin, and 0.10–20 ng/mL for N-acetyltryptamine, with correlation coefficients ranging from 0.954 for N-acetyltryptamine to 0.997 for tryptamine.

The intraday and interday precision remained consistently below 15 % for all analytes. Most analytes met the accuracy criteria, except for N-acetyltryptamine at the lowest quality control level (0.2 ng/mL), where the intraday and interday accuracy were 22.4 % and 17.4 %, respectively.

In conclusion, this novel method allows for rapid identification of tryptophan-melatonin pathway intermediates in less than ten minutes, including seven distinct melatonin-related analytes. This suggests that it may find use in everyday clinical and scientific endeavours.
LINK

 

Discussion thread for study, Targeted analysis of seven selected tryptophan-melatonin metabolites: Simultaneous quantification of plasma analytes …, 2025, Kaleta+

 

I seem to remember Ron Davis getting a sizeable grant to do genetic work on ME/CFS? Am I misremembering this or did something get published?

 

The only genetics paper i remember is the SIPS one from a very small number of patients. No capacity to hunt it down now apologies.

 

Science lesson in the OMF newsletter:

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Words like metabolomics and proteomics are thrown around a lot in the ME/CFS research world, especially because the results from these kinds of analyses have the potential to contribute to a better understanding of what’s really going on in ME/CFS and to identify a biomarker for the disease. For this month’s research process email, I therefore want to dive into the metabolomics world (we’ll plan to cover proteomics at another time).

The Heart of the Matter

• Metabolomics is the study of small molecules called metabolites in biological samples.
• Measuring metabolites involved in a specific metabolic pathway can help identify when that pathway isn’t performing its function properly. Using metabolomics to study energy metabolism is particularly relevant in ME/CFS, when energy production is faulty.
• Metabolite levels are typically measured through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).
• The OMF Melbourne ME/CFS Collaboration often focuses on metabolic studies, including one trying to understand the metabolic differences between ME/CFS and two of its common comorbidities: irritable bowel syndrome (IBS) and fibromyalgia.

What is Metabolomics?
Metabolomics is the study of small molecules called metabolites in biological samples. Studying these molecules helps us understand what the body is actually able to do.

What is a metabolic pathway?
A metabolic pathway is a series of chemical reactions that perform a specific function (e.g., produce energy). A chemical reaction takes one or more molecules (reactants) and turns them into another molecule (product). The reactants and products in a metabolic pathway are called metabolites. Therefore, metabolomics is a way of measuring what chemical reactions are taking place, or how a metabolic pathway is behaving.

How is metabolomics used in ME/CFS research?
Take energy metabolism as an example of where metabolomics tells an important story in ME/CFS and related conditions. There are three major metabolic pathways that produce energy in the form of ATP: glycolysis, the TCA cycle, and OXPHOS. Glycolysis, for example, takes glucose (the reactant) and turns it into pyruvate (a product), creating ATP along the way. This metabolic pathway might not work properly in ME/CFS, though. Performing metabolomics to measure the metabolites, or the reactants and products, involved in glycolysis can tell us if the pathway is behaving abnormally.

How do you measure metabolites?
Metabolomics is typically measured through two techniques: nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). NMR spectroscopy sends radio waves into a sample and measures how the molecules in the sample interact with those waves. Different molecules interact with the waves differently, so the signal that’s produced helps identify specific molecules in that sample. In MS, the sample is modified so the molecules become positively charged. They are then moved through a device using an electric or magnetic field. The molecules will separate based on the ratio of their size to how positively charged they are, therefore helping identify which molecules are in the sample.

The OMF Melbourne ME/CFS Collaboration often focuses on metabolic studies, which typically include NMR and MS metabolomics analyses. One such study tries to understand the metabolic differences between ME/CFS and two of its common comorbidities: irritable bowel syndrome (IBS) and fibromyalgia. To read more about this study, click here.