New insights into ME/CFS found in Latham female cells

The cause of ME/CFS is unknown, although many people develop symptoms after a long illness. Long COVID, the long-lasting illness after being infected with COVID-19, has many similarities. Tweenham believes her symptoms began after she contracted a mild case of mononucleosis in high school.

“I didn’t fully regain my energy,” she said.

Throughout her late teens and early twenties, Twinam would experience periods of fatigue. As a student and young adult, she dealt with this by having weekend meltdowns. Then, at 28, she was diagnosed with breast cancer. Fatigue and other symptoms have been attributed to the disease and chemotherapy.

“Things have been going downhill ever since,” said Twinum, whose case was previously reported by The Washington Post.

After stopping chemotherapy and appearing to be stable, symptoms returned about 10 years ago. Twinam tried various treatments. She was diagnosed with lupus, poorly differentiated connective tissue disease, and Sjogren’s syndrome. Nothing went anywhere except for a 2015 diagnosis of Li-Fraumeni syndrome, a rare genetic disorder that increases the risk of cancer. His father and brother were also found to carry the gene.

From 2012 to 2015, Twinam returned to school to pursue a master’s degree in public health. She’s been doing research. In December 2016, she was reading an article by Paul Hwang, a scientist at the National Institutes of Health, about cellular metabolism in patients with Li-Fraumeni syndrome. Chronic fatigue has nothing to do with the disease; instead, studies have found that it increases the amount of energy produced. Twinam sent Hwang an email asking if Li-Fraumeni syndrome could have the opposite effect, as it did in her case.

“I didn’t expect him to get back to me,” Twinum said. “He got back to me right away.”

Over the next few years, Twinum visited the National Institutes of Health clinic in Bethesda, Maryland. The day after flying home from her first trip, she received an email.

“I think we might have an explanation,” he said.

According to research published this summer, Twinam’s cells produced too much of a protein called Wiskott-Aldrich syndrome protein family member 3 (WASF3), rather than the factor associated with Li-Fraumeni syndrome. Huang explained to the Times Union in an email that the protein impairs the cells’ ability to produce energy. Hwang said that while WASF3 is not thought to be the cause of ME/CFS, for at least some people with the disease, WASF3 may be a factor in muscles not working properly. Researchers are now studying how to lower WASF3 levels in patients.

“I’m essentially just providing them with cellular material,” Twinum said. “That really led to this possible breakthrough.”

As little as a walk, as tiring as a marathon

According to the CDC, the number of Americans with ME/CFS is believed to be between 836,000 and 2.5 million. Jaime Seltzer, director of science and medical outreach at the advocacy group ME Action Network, believes that number could quadruple in the wake of the pandemic, given the overlap in symptoms and causes of ME/CFS and Long COVID.

ME/CFS is associated with a range of symptoms, including cognitive problems, sleep disturbances and difficulty sitting up straight. One tell-tale sign is post-exertion malaise, where even a small amount of activity can leave a person exhausted for an extended period of time. Twinum likened it to having her limbs turn to cement, or waking up in the middle of the night to find her legs burning after she’d run thousands of meters.

“Going too far doesn’t mean I can run a marathon,” she said. “It could be as simple as me going to the mall.”

Seltzer noted that one in four ME/CFS patients is homebound or bedridden. Only 13% are able to work full-time. Twinam considers herself lucky to have found a job that works part-time and has a flexible schedule. She has not yet received a diagnosis, except for a note left in her file by her rheumatologist. A lack of biomarkers, little research and stigma means most people go undiagnosed.

“People often end up having to quit their jobs and lose relationships,” Seltzer said. “Long before they knew what was going on.”

Overexertion can exacerbate and worsen symptoms. For those suspected of having ME/CFS, ME Action has published guidance on pacing activities.

ME Action communications manager Adriane Tillman said: “You can keep pushing, pushing and bumping so that you never recover from the same baseline.”

Tillman, Seltzer and Hwang all pointed out that this study does not mean the end of ME/CFS. Huang said there may be other factors contributing to fatigue, and COVID-19 patients have not yet been tested. Research into treatments is a current priority, but a specific timeline is unclear.

For Twinam, even this discovery – and subsequent treatment research – came as a relief. Since Washington Post science reporter Brian Varstag first reported the story, she has received messages from others sharing their own stories.

“I think people are very optimistic,” she said. “Maybe there will be a breakthrough.”