Chris Armstrong PhD (biochemistry and molecular biology) was there at the beginning of the metabolomics field in chronic fatigue syndrome (ME/CFS). In fact, Armstrong was the lead author of the first ME/CFS metabolomics study published in 2012.
I asked him how he got started in ME/CFS. He said ME/CFS was a good fit for him in a number of ways. For one, he was interested in the role of energy metabolism in chronic disease – a field that has only grown in importance in ME/CFS over the past ten years – and which occupies his thinking more and more.
Metabolomics, with its focus on what’s happening in the metabolism right now, potentially provides an excellent way to get at the functional underpinnings of disease. Our metabolism, for instance, shifts all the time, in response to exertion or infection or digestion – making metabolomics a good fit for studying the energy metabolism problems in ME/CFS and symptoms like PEM.
After a couple of years working with Ron Davis and the Open Medicine Foundation in the US, Armstrong said he welcomed his return to Australia to open, in collaboration with EMERGE Australia, the 5th Open Medicine Foundation-funded research center. He’s got access to all the equipment he needs, he’s been successful in government and philanthropic grant applications, the cost of doing research is relatively less expensive, and the formation of the Australian ME/CFS Biobank was another plus.
The idea is to do more with less, and right now Armstrong actually has more. In fact, Armstrong has been on something of a roll regarding getting his ME/CFS grant applications funded. Scouring the ground for possible funding, Armstrong somehow landed grants from more than 5 different funding sources (federal/state sources, philanthropy) and is now, get this, collaborating on 15-20 separate studies. The new Australian ME/CFS research center may be new, but it is already very busy.
The “Crash Course” Studies
A longitudinal study that tracks how metabolites change over time in response to good/bad days in ME/CFS has been on Armstrong’s wish list for years. Armstrong predicts that the study will help uncover some of the biological underpinnings that are driving key symptoms such as post-exertional malaise.
Finger-prick blood and urine samples in combination with wearables (to assess sleep, activity, blood pressure and heart rhythm) and surveys will enable researchers to find out which parts of ME/CFS patients’ metabolism go screwy when they crash. Those, in turn, will provide a roadmap they can use to dig deeper, hopefully, into the core problems in ME/CFS. They expect to have preliminary data available by next year.
Armstrong is currently collaborating with the multiple teams to initiate a longitudinal study on pediatric ME/CFS patients in Melbourne and a 3-month adult study called the “Crash Course” that follows ME/CFS, Long COVID, and Chronic Lyme disease at Stanford.
Another study will attempt to determine fundamental elements ME/CFS patients’ cells may be missing/ hungering for. ME/CFS patients’ and healthy controls’ cells will be put in different media and then tracked. Armstrong and his team will then add in their compounds of choice – such as big players in energy metabolism like hydroxybutyrate, glutamine, glucose – tag them – and then, in an effort to see where the breakdown in energy metabolism occurs – follow them.
An ME/CFS cell that starts sucking up one kind of media could inform us about a compound that is, in a very fundamental way, missing in our cells.
An ME/CFS cell that feeds voraciously on all sorts of substrates, on the other hand, might be working overtime simply to stay alive. It’s possible, in other words, that our cells are starving in a field of plenty. In an effort to compensate for a broken energy production system, they may be taking in more resources than usual. That would jive with findings from the early metabolomic studies which uncovered a similar profile to that seen in starvation. Armstrong reported that the “starvation” finding seems to be holding up and corroborates well with Fisher’s recent finding of inefficient ATP production in ME/CFS.
Looking For Waldo
Thanks to a nice donation, Armstrong is also following up on a unique hypothesis in ME/CFS that could explain those energy production problems. In fact, Armstrong’s “Looking for Waldo” study appears to be the first of its kind done in any disease.
It probably comes as no surprise that excess ammonia can be a problem. When a dysfunctional liver fails to break down nitrogen, excess ammonia can produce neuroinflammation and encephalopathy. Nobody, until now, has applied the excess ammonia issue to cells.
Armstrong glommed onto his cellular ammonia accumulation hypothesis when metabolomic studies suggested that people with ME/CFS were using amino acids for fuel at a faster rate than healthy controls.
Amino acids are usually used for fuel at an elevated rate during a stress response or starvation. When you’re starving, for instance, your body will save your carbohydrates to make sure your brain and immune system are getting them. The rest of your body will use fats and amino acids in greater proportions. The long-term use of amino acids for energy will reduce digestive enzyme production and break down muscles and connective tissues.
For some reason, people with ME/CFS also appear to be preferentially turning to amino acids to power their cells. That presents a potential problem because amino acids have this pesky nitrogen atom attached to them that needs to be taken care of. The body usually eliminates the nitrogen from amino acids in a variety of “safe” forms, but the ME/CFS metabolomic studies are not finding as much of these “safe” forms as expected.
That suggests that all that nitrogen is being eliminated all right – but in “unsafe” forms such as ammonia or peroxynitrite – two highly reactive compounds that can wreak havoc in our cellular energy production system.
In this novel study, Armstrong is tracking the molecules in cells to see what happens to nitrogen as it passes through the energy production systems found in ME/CFS. These cells will be grown and monitored in more stressful and less stressful conditions. The way these cells use amino acids, sugars, and fats for energy production will be compared between the ME/CFS and healthy participants.
Do the Eyes Have it? The Ocular Motor Project
The Ocular Motor Project falls into the “Isn’t technology great?” or “What will they think of next?” categories. Whether or not the eyes are windows to the soul may be debated, but they can certainly function as windows to our health.
It turns out that humans devote an unusually large part of our brains (50-80%) to visual processing. Simply the act of following a dot across a screen requires that multiple systems work together properly. It takes, for instance, sensory processing to direct the eyes to move, muscles to move them, pupil dilation/contraction to adjust to the light present, etc.
Tracking anything that complicated can reveal a lot about neurological and other diseases. This is the first time, though, it’s being applied in ME/CFS. The project is already producing some very interesting findings indicating that some sort of pathology is present. Armstrong and collaborators hope to develop their findings into a diagnostic or objective marker for ME/CFS and its symptoms.
The tool may even be able to pick up the early fatigability and exertion intolerance that occurs as the eyes (and brains) of people with ME/CFS tire over time. Thus far, Armstrong is finding, in contrast to healthy controls, that the eyes of people with ME/CFS get worse over time at following that dot – leading to the possibility that the Ocular Motor Project could lead to the first easy test for exertion intolerance.
Chris Armstrong and the 5th Open Medicine Foundation-funded research center in Australia are on something of a roll. Armstrong is continuing his focus on energy metabolism as he and his team try to understand the metabolic underpinnings of ME/CFS. If all goes well, we should learn more about why people with ME/CFS are so susceptible to crashes, why their cells may be starving (and what they are starving for), and if excess ammonia is wreaking havoc on cellular energy production. Plus, the eye study could potentially provide a cheap and accessible diagnostic test.
HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT