Montreal researchers link protein to chronic fatigue

Montreal Gazette

22-07-2025

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A Université de Montréal professor and his team believe they have made a breakthrough discovery about a poorly understood illness that affects thousands of Quebecers and has significant ties to long COVID.
In a recently published study, Dr. Alain Moreau identifies a potential new biomarker and therapeutic target for myalgic encephalomyelitis (ME/CFS), once known as chronic fatigue syndrome.
It's an advancement he says could revolutionize the diagnosis and treatment of the illness.
'It is very, very encouraging,' Moreau said in an interview, explaining the findings were 10 years in the making. 'We believe it can bring a lot of hope to patients.'
ME/CFS is a complex disorder often triggered by viral infection. It can strike a person's muscular, nervous and immune systems and can become disabling, with many patients unable to work or confined to bed as a result.
Though it can attack the body in different ways, its cardinal symptom is what's known as 'post-exertional malaise' — a worsening of symptoms, or appearance of new ones, after minimal physical or mental exertion.
Moreau's study focused on a protein known as SMPDL3B.
Though usually found attached to cell membranes, where it plays a role in controlling the immune system's response, it can also become detached and found in blood plasma.
The study identified that people with ME/CFS have elevated levels of the soluble form of the protein in their plasma. The higher the levels, the more severe their symptoms.
Those elevated levels could be caused by a specific enzyme, PI-PLC, that detaches the protein from the cell membrane and disrupts immune regulation.
Critically, Moreau said, there are known diabetes drugs that can inhibit PI-PLC's activity.
'In other words,' Moreau said, 'this discovery shows that two medications currently in use — two molecules that are now even produced in generic formats — may be of interest for the treatment of myalgic encephalomyelitis.'
The study also identified that the levels of SMPDL3B found in people's plasma is influenced by estrogen, which could explain why women are so disproportionately affected by ME/CFS and why some experience an improvement in symptoms with age.
The study included a cohort of 249 ME/CFS patients from Quebec, all recruited before the COVID-19 pandemic, and was tested against a cohort of 141 Norwegian patients.
'We reached exactly the same conclusion in both: that elevated levels of soluble form was associated with symptom severity and also that women had much higher levels,' Moreau said.
The study was first published in the Journal of Translational Medicine earlier this month. Moreau stressed that randomized clinical trials are needed to confirm and apply the findings moving forward.
Potential for long COVID patients
While promising for ME/CFS patients, Moreau believes the findings could also have important implications for long COVID patients, who often experience similar symptoms.
The link between the two illnesses first started emerging after the early waves of the pandemic. As people shared stories of persistent COVID symptoms that worsened after exertion, ME/CFS patients recognized what they were going through.
Today, it's believed that nearly half of the people suffering from long COVID meet the diagnostic criteria for ME/CFS. In both cases, women are disproportionately affected.
While the number of ME/CFS patients in Quebec used to be estimated at 70,000, Moreau believes that post-pandemic, it is now likely more than 100,000 people.
He hopes the findings can be encouraging to people suffering from both conditions.
'We are trying to contribute to the research and make a difference,' he said.