Cort Johnson from the Health Rising blog looks at the work of two researchers, with projects currently funded by ME Research UK, who are innovating in their respective fields as they tackle some of the big questions in ME/CFS.
Creative beyond its means
What kinds of researchers tackle the neglected but fascinating field of ME/CFS? The answer to this question also provides an answer to another question – why does the field often seem to be creative beyond its means?
When I asked Jarred Younger why, of all the fields available to him, he chose chronic pain and fatigue to focus on, he stated that it was the place he felt he could make the biggest difference. The fact that it is also largely neglected was immaterial for him. Confident in his ability to make a difference, he moved forward – and that has made all the difference.
ME/CFS has never been the field of choice for the cautious, paint-by-numbers type of researcher. It’s more a field for pioneers and fresh thinkers. Just being part of it requires some boldness, and with that boldness often comes creativity and the willingness to swing out.
Two ME/CFS researchers, Jarred Younger and Bhupesh Prusty, both of whom are currently being funded by MERUK, provide examples of scientists who have been willing to swing out, and in doing so may be opening opportunities not just for ME/CFS but for other diseases as well.
Jarred Younger – the technology innovator
Eight years ago, Younger left one of the top medical schools in the USA at Stanford University to run his own Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama at Birmingham. Since then, he’s embarked on a novel course of ME/CFS research that could impact the world of neuroscience.
He was the first to attempt to use magnetic resonance imaging to produce heat maps of the brain (thermography), to determine whether inflammation is present, and he is in the middle of a large multi-year NIH grant to determine if this approach works. If it does, Younger will have invented a way to study neuroinflammation that’s considerably cheaper, more accurate and safer than current methods, and he will have done it while focused primarily on ME/CFS.
As novel as Younger’s thermography approach is, it’s simple compared to his next trick – finding a way to determine if immune cells from the bodies of ME/CFS patients are making their way to their brains.
ME Research UK probably couldn’t have imagined when it agreed to fund Younger’s study five years ago that it would take this long to come to fruition. But that’s what happens when every part of an effort is new. Younger had to find new ways to take out the white blood cells, separate them, put a radiotracer inside them, put them back in, have them go on about their business as usual, and then measure them. The study was so fraught with potential complications that it took five years for it to get past regulatory hurdles in the USA.
Finding immune cells from the body in the brains of ME/CFS patients could explain a lot. They don’t belong there, and don’t get asked in unless something has gone really wrong. And when these cells get to the brain they act like bulls in a china shop. Sure, they might be able to knock out an invader but the cost would be high indeed. Alternatively, they could be sneaking into the brain via leaks in the blood-brain barrier.
However they might get there, finding these immune cells in the brains of ME/CFS patients would indicate that a “severe pathological inflammation” has taken place. That finding would undoubtedly revolutionise how we think of ME/CFS.
Younger recently tested his technique in healthy controls and has found that it works. The next step is to apply it in ME/CFS patients, and we are all excitedly waiting for his findings.
Bhupesh Prusty – the innovative thinker
As Jarred Younger has pushed our technological boundaries, Bhupesh Prusty has been redefining how we think about ME/CFS, and potentially how we think about viral diseases.
The effect viruses have on the body has traditionally been linked to ‘viral load’ – the amount of virus present. If viral loads are not increased the virus is generally thought not to be a problem. That’s posed something of a conundrum in ME/CFS where viruses clearly trigger the disease but viral loads tend to be low.
Prusty’s 2018 study, though, threw the viral load idea on its head by showing that, even before they begin to replicate, herpesviruses may be producing small bits of RNA that are fragmenting the mitochondria in the cells. Suddenly it seemed possible for even a seemingly latent virus to produce an energy crash.
Earlier, Bob Naviaux had come up with a similar hypothesis which proposed that virally infected cells in ME/CFS had shut down their mitochondria, leaving them in a hypometabolic state. In 2020, Prusty and Naviaux teamed up in a laboratory experiment to show that virally infected cells might be flooding the serum of ME/CFS patients with an unknown factor that is able to fragment the mitochondria of other cells and put them into an antiviral state.
The following year, ME Research UK jumped in, funding Prusty in his efforts to identify the mysterious factor(s) in ME/CFS patients’ serum that appears to be knocking out the mitochondria of other cells. Prusty appears to have made progress – and not just with the mitochondria.
In his recent talk at the Charité conference in Germany and the Invest in ME Conference in London, he focused on two factors – a substance called fibronectin and IgM antibodies – which he believes together could help explain the mitochondrial as well as the blood vessel and clotting problems found in ME/CFS.
Walter Koroshetz, the director of the massive National Institute of Neurological Disorders and Stroke (NINDS) in the NIH in the USA, has said that he doesn’t believe the answer to ME/CFS is going to come from the NIH. It wasn’t clear why he said that, but one suspects it may have something to do with creativity going to die in large organisations.
Small, focused organisations like ME Research UK are perfect, though, at filling that creativity gap and igniting sparks that have the potential to cast a whole new light on ME/CFS. May it be so.