Sanna Stella
Stacy Wescott/TNS via Getty Images
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Stacy Wescott/TNS via Getty Images
Sanna Stella
Stacy Wescott/TNS via Getty Images
Long before the world heard of the lingering coronavirus, Sanna Stella experienced firsthand how a simple respiratory infection could turn into a chronic disease.
In 2014, Stella, a therapist in the Chicago area, suffered from debilitating fatigue caused by bronchitis.
Within a month, she could barely walk from the couch to the kitchen table. Eventually, Stella learned that she had Chronic Fatigue Syndrome, now called Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, or simply ME/CFS.
Patients may experience a variety of symptoms, including extreme fatigue, brain fog, and post-exercise fatigue (worsening of symptoms after exercise). There is no FDA-approved treatment for the disease, which affects more than 4 million people in the United States.
Even with a formal diagnosis, Stella's daily reality changed little. “She was very frustrated and angry that she would be stuck in bed and no one would be able to do anything,” she said.
She decided to focus her energy on advancing understanding of the disease. So when she was selected to participate in an ambitious study led by the National Institutes of Health, Stella was determined to take part, even though she knew it would be physically taxing. I made it.
“Everything was pretty tough,” she says. “After her first four or five days, we could only test her on a stretcher, but I wanted to be able to contribute to our progress.”
Seven years later, the study was finally published in a journal. nature communications this week. This book provides an unusually comprehensive look at the biological abnormalities that can occur in ME/CFS, spanning the brain, gut, immune system, and autonomic nervous system.
A deep look into a long-ignored disease
The findings emphasize that symptoms cannot be explained by physical deterioration or psychological factors, said lead author Dr. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke.
“We can strongly say that's not the case. There are real biological differences,” he says.
The results confirm much of what those in the field already know, but this data-rich snapshot of the disease is a sign of how deeply we are investigating the disease and testing potential treatments. stands out because it has the potential to bring new momentum to the
Dr. Nancy Klimas calls this the most thorough evaluation of any disease she has ever seen in clinical research.
“This is great research,” says Klimas, director of the Institute for Neuroimmune Medicine at Nova Southeastern University in Florida. “This is the kind of data set that could actually lead to clinical trials. [for new treatments] And that's what our patients want most. ”
The study, which began in 2016, was interrupted by the coronavirus pandemic, slowing progress and limiting the number of participants, with only 17 ME/CFS patients ultimately participating.
Still, because of the overlap between ME/CFS and long-term coronavirus symptoms, the findings may actually garner more attention than they otherwise would.
The exact root cause of ME/CFS is unknown, but there are many theories. Many, but not all, cases appear to develop in the aftermath of an acute infection, such as with the Epstein-Barr virus or other bugs.
Maureen Hanson, a professor of molecular biology and genetics at Cornell University, said research has stalled for decades, vilified as “purely psychological,” and to date, few clinical trials have been conducted. It is said that this has not been done.
Better understanding of the immune system 'at war'
The NIH intramural study involved more than 75 scientists and cost millions of dollars to complete.
Participants were carefully selected from a pool of over 200 patients to ensure the correct diagnosis was obtained and traced back to infection. Detailed psychological and medical evaluations were also performed.
Enrollees spent several weeks at the NIH Clinical Center in Bethesda, Maryland, undergoing a battery of tests ranging from muscle biopsies to time spent in a tightly controlled metabolic chamber.
The authors conclude that ME/CFS is primarily a brain disorder, likely caused by immune dysfunction and changes in the gut microbiota.
Dr. Anthony Comaroff, who studies ME/CFS at Harvard Medical School, says this is completely consistent with existing research.
The study provides compelling evidence that the immune system is chronically activated, he said, adding, “It's almost as if we're fighting a long war with foreign microbes, one that we can't quite win.” “It's like we're in a war that had to go on.”
Nass and his co-authors say the findings suggest that antigens, leftovers from infections, continue to confuse the immune system. This “chronic antigenic stimulation” triggers a series of physiological events that ultimately manifest as symptoms.
This is a theory based on work by researchers like Hanson who have found evidence of T-cell dysfunction, or “fatigue,” when these immune cells are continuously exposed to the same antigen. It is a malfunction that can occur.
“When they're exhausted, they can't do their job of fighting pathogens, which is an important consequence of chronic infection,” Dr. Hanson says.
She says this theory has gained traction in both ME/CFS and long-term COVID-19, but there are other possibilities as well. The infection may cause an autoimmune response or cause problems with the immune system in some way.
“It's probably all three things happening,” she says.
understand fatigue
The study also takes a closer look at how dysfunction in the brain and nervous system helps explain cognitive and physical symptoms such as fatigue.
Many people with ME/CFS “have learned that if you take it too far, you'll relapse,” Klimas says.
Spinal fluid samples revealed abnormally low levels of certain neurotransmitters, such as dopamine, and other molecules involved in regulating the nervous system, suggesting that these deficiencies are associated with the symptoms. found.
The researchers also looked at differences in brain activity during repeated tests of physical tasks, in this case grip strength.
Brain regions involved in fatigue perception and effort generation were less active in ME/CFS patients.
“Their brain is saying, 'No, don't do it.' It's not a spontaneous phenomenon,” Nass says.
This is a new observation that shows that brain abnormalities can make it difficult for ME/CFS patients to exert physical or mental effort, Comaroff said.
“It's like trying to swim against the current,” he says.
Limitations and future direction
Despite the vast amount of data collected, the small number of participants in the study and its strict inclusion criteria mean that the results do not necessarily generalize to the broader ME/CFS patient population. Masu.
First, participants had to be healthy enough to travel and undergo extensive testing.
“These patients are not necessarily as sick as many ME/CFS patients,” says Dr. Lucinda Bateman, medical director of the Bateman Horn Center in Utah, which treats ME/CFS patients.
Bateman said the study was well-executed and comprehensive, but nothing groundbreaking. But she hopes the data can serve as a “foundation” for future research.
There were also some notable gaps in what the study found. For example, there was no evidence of autoimmunity recorded elsewhere.
Given its small size, it's difficult to conclude that “what this study didn't find doesn't actually exist,” Komarov said.
Ms Bateman said she was disappointed that the team did not perform additional exercise tests that could have revealed more post-exercise fatigue. It is an escalation of the disease that develops days after the patient overdoes it.
“That's what makes people not want to put in the effort,” she says. “We know that if we take that test again the next day, we won't be able to match our performance on that test with the same amount of physiological effort.”. ”
Seeds for future therapeutic trials
Now that the long-awaited study results have been released, the question for many patients is: what to do next?
The NIH team has proposed immune checkpoint inhibitors, a type of anti-cancer drug, as one option that could be investigated for ME/CFS.
Nass noted that the NIH has already begun clinical trials of intravenous immunoglobulin (IVIG) in patients with long-term COVID-19 infection, which could also help research on ME/CFS. Says.
Although these symptoms have striking similarities, Hanson believes the two cannot be considered completely interchangeable.
“We need to study long-term coronaviruses as a group and ME/CFS as a group and compare these two groups, not just mix them together,” she says.
She and Bateman are helping design a roadmap to set federal research priorities for ME/CFS, an effort she hopes will lead to more funding for clinical trials.
“There is a real urgency to start clinical trials for people who have had the disease for decades, many of whom have lost most of their adult lives to this disease,” she says.
