The ICanCME Collaborative Conference on Myalgic Encephalomyelitis (ME) is a virtual conference driven by people with ME and their loved ones held between November 4th and November 6th. The conference is fully virtual and free to make it more accessible to people with ME. For the play-by-play, I posted live alongside the talks.

The third day of talks focused around the theme of “Collective Deep Thinking in ME Research Design.” To make it succinct, I summarize the main points of the talks below. For more details, you can view my thread on X or BlueSky.

Todd Davenport, Professor at University of the Pacific | Critical Thinking in Research Design

Davenport starts his talk with some background on ME research so far.

Although there’s a rapidly growing increase in the number of ME cases worldwide, research funding for the disease is poor and there aren’t any approved biomarker tests or treatments. Long COVID boosted interest and research funding into ME as well, but a lot of that funding has now gone away.

Many people infected with SARS-CoV-2 develop ME. “I don’t think all Long COVID is ME, but there is ME in Long COVID,” said Davenport. Based on some studies he references, about one in four people with Long COVID also qualify for ME.

Why has there been so little progress? Many researchers aren’t looking at post-exertional malaise (PEM). Most studies of ME between 2018 and 2023 used definitions of the disease that don’t require PEM. When you use these definitions, you end up with bad research, like the PACE trial, where many of the participants might not even have ME.

Next is evaluating PEM. “It’s science and art,” Davenport explained. The DSQ-PEM questionnaire and supplementary questions can screen in patients into trials with PEM but isn’t fit as an outcome measure. FUNCAP and PAQ, which are developed with PEM in mind may be useful to track outcomes in trials.

His talk also focused on the importance of finding subgroups that respond to specific treatment, and validating them. The subgroup analysis you want to do needs to be laid out beforehand, rather than fiddling with data until you find something. Then, these would need to be validated in other populations.

Once these are validated, we can run larger and more efficient trials but we need to ensure they are equitable, accessible, and inclusive across disease severities.

Jacqueline Becker, Clinical Neuropsychologist at Mount Sinai | Cognitive Testing in ME

Becker talked about the importance of proper neurocognitive testing. The holy grail is developing tools that capture what patients experience accurately.

Many people with ME or Long COVID report cognitive problems, but they’re sometimes hard to spot on typical tests. She thinks it is important to take a look at all the cognitive domains, including attention, language, memory, and executive function. Sometimes memory problems aren't caused by problems with memory, but issues with other cognitive domains. For example, getting fatigued really easily could affect the memory rather than the memory being faulty itself. But it takes more time and effort to do this.

Importantly, normal cognitive test results doesn’t mean there’s nothing wrong. Many tests aren’t designed to detect subtle impairments. Someone who tests normal may have declined substantially since developing ME.

Alain Moreau, Professor at University of Montréal | Precision Medicine for ME

Moreau conducts “deep phenotyping” on people with ME to look for different proteins in the blood that might provide clues about what’s driving the disease.

He believes that a “post-hoc molecular autopsy” where researchers look to see whether there is a subset of patients where a treatment worked is important. Like many other researchers, he expects that there will be biomarkers that stratify patients.

Moreau discussed some examples of findings his team has found. There’s the PREDICT-ME blood test that discriminates between fibromyalgia and ME with high accuracy, and other work that stratified patients through other proteins like SMPDL3B and haptoglobin.

In his view, you need to find groups of patients with elevated biomarkers and test whether drugs that normalize them treat the symptoms. However, we don’t know that these proteins are driving the disease or if they’re the body’s response to ME.

David Putrino, Director at ICahn School of Medicine at Mount Sinai | Adaptive Clinical Trials and Accessibility in Research Design

Putrino also discussed the importance of stratifying patients in trials. After trying out treatments in small numbers of patients, responder analysis might help find a working treatment.

He brought up the example of daratumumab. In a pilot of 10 patients with ME, the drug which acts on B cells. In people who had higher levels of another immune cell, called the Natural Killer cell, the drug appeared to work. That provided the basis for the researchers to set up a larger Phase 2 trial in people with ME who have higher numbers of Natural Killer cells.

Putrino also thinks that adaptive trials make a lot of sense. They’re expensive and hard to run because they involve multiple simultaneous study arms testing multiple interventions or combinations of treatments. After a little while, researchers can see whether any of the treatments are futile, and drop those arms of the study. This could make finding treatments for the right subpopulation faster.

Putrino also advocated for new technology that monitors activity, glucose, cytokines and other factors as ways to track patients throughout these trials. He doesn’t think its necessary to run a 2-day cardiopulmonary test to induce PEM (though I haven’t seen a lot of clinical trials actually doing that). He also thinks its important to bank biosamples. Someone might want to reanalyze data in the future and find something the original researchers missed.

Michael VanElzakker, Assistant Professor at Harvard Medical School | Neuroinflammation in ME

VanElzakker focused on neuroimaging findings in healthy controls, Long COVID and ME. His team looked at the brain’s immune cells, the microglia, which change their shape entering an activated state after infection.

In various research studies, he and other researchers have found higher levels of activated microglia across different regions of the brain and brainstem. Some of the activation is correlated to impairments in top-down cognitive tasks that might explain difficulties with concentration.

They also looked at white blood cells called neutrophils from these participants. In ME, but not in Long COVID, they showed 5 percent more movement toward bacteria. It is unclear what this small difference means. They also spotted differences between Long COVID and ME in the the pupillary response to light.

Carrie Anna McGinn and Trudy Flynn | Patient Engagement in ME Research

McGinn and Flynn provided a crash course in patient engagement. Proper patient engagement goes beyond including them as a token. It involves meaningfully including them in the research process to design and shape trials.

As a partner, patients should have shared power with researchers. Their lived experience and expertise can contribute to make research better. And they should be fairly compensated for their contributions. Patient partnership reduces the potential harms to participants, demonstrates respect, and cultivates inclusion and accessibility.

Dr. Daisy Fung | Addressing Ableism/Internalized Ableism in Research and Clinical Settings

Fung’s talk involved a lot of basic definitions of disability and ableism. She emphasized that disability and disabled are neutral terms, that disability is dynamic and fluctuates, and due to ableism, many people mask their symptoms day-to-day.

Masking occurs in part because of ableism, which assigns values to people’s bodies and minds based on societally constructed ideas of normalcy, productivity, intelligence, excellence, fitness. These ideas, as the speaker explained, are rooted in eugenics, anti-Blackness, misogyny, colonialism, imperialism, and capitalism. Importantly, “you do not have to be disabled to experience ableism,” since it functions as a system that assigns value to people based on perception and assumption.

Fung defined the idea of internalized ableism and obsession, which occurs when disabled people start to have ableist beliefs, and sometimes reflect it onto others in the disabled community. She also talked about the intersectionality of privilege and identity, and how doctors and researchers need to understand these factors when they’re interacting with patients and participants.

When “the wrong people are asking the wrong questions, and wrong guidelines come out as a result,” Fung said. Using diabetes research as an example, she noted that studies focus on compliance rather than understanding patient experiences or desires. Disabled people remain excluded from health education and research, perpetuating discrimination by peers and professors — and ultimately undermining both care quality and research quality.

Fung also connected these ideas to social media and why patients might self-diagnose. “TikTok trends exist because patients are turned away by our own profession and society,” Fung said.

So how can clinicians and researchers take these factors into account? Clinicians were encouraged to ask patients what accommodations they need: turn down bright lights, record sessions, offer virtual or shorter appointments, eliminate punitive cancellation policies. “Be flexible, different is not worse.” She ended with a reminder that advocacy is part of a doctor’s work. “It’s okay to say I don’t know, but we need to follow it up.”

Tess Falor and Isabel Burnett-Ramirez, Renegade Research | Patient Driven Lactate Research in ME

Falor and Burnett-Ramirez discussed the findings of #TheAcidTest. People in the patient community read research about differences in lactate across ME. Lactate produced as a by-product when the body is breaking down glucose in an oxygen-starved environment. Lactate buildup is the reason we feel sore after working out.

At rest people have low levels of lactate (<2 mmol/L). The patient-led project aimed to test whether there were differences in lactate at baseline and whether it correlated to symptoms. They ordered lactate meters, mailed them out around the world.

Using home finger-prick devices, participants collected samples right after waking and one hour after a light breakfast. For some, this was the first sort of test they’ve done that showed any abnormality. Todd Davenport organized the IRB and survey infrastructure, enabling people to securely upload results and answer questions. The study also allowed for patients who had severe forms of ME to participate. They found that on “bad days”, the levels of lactate were elevated.

The team is currently writing up the study, and is looking toward running more decentralized trials, as well as testing interventions that could normalize lactate levels and potentially treat symptoms.

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I'm a science and health journalist who is disappointed and fed up with the lack of news coverage surrounding Long COVID, ME/CFS, chronic illness, and disability issues in Canada. I decided to start this newsletter to provide a home for the news stories that don’t get coverage in Canada’s news ecosystem, which lacks outlets for good, science-based reporting.