Lawyer’s ‘dogged efforts’ led to scientific discovery that could help with chronic fatigue

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Personal Lives Lawyer's 'dogged efforts' led to scientific discovery that could help with chronic fatigue

By Debra Cassens Weiss

September 21, 2023, 11:03 am CDT

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“Amazing findings in medicine are sometimes based on one patient,” said Paul Hwang, a researcher at the National Institutes of Health. Image from Shutterstock.

A lawyer who had to reduce her workload because of fatigue, neuropathy and muscular weakness embarked on a quest to discover what was wrong with her.

Albany, New York, lawyer Amanda Twinam had initial problems with fatigue after mononucleosis in high school. She also had two bouts with breast cancer, a marker for autoimmune disorders in her blood and a genetic cancer disorder called Li-Fraumeni syndrome, the Washington Post reports.

Twinam, who also had a master’s degree in public health, spent years trying to figure out the reason for her problems.

“Her dogged efforts led to a new scientific discovery at the National Institutes of Health and a promising new line of research that may end up helping many other people with chronically fatiguing illnesses, possibly including long COVID,” the Washington Post reports.

Twinam’s quest led her to a journal article about Li-Fraumeni syndrome in 2016 written by Paul Hwang, a researcher at the National Institutes of Health. The article said cellular mitochondria produce too much energy in people with Li-Fraumeni syndrome.

Twinam wondered whether her cells had the opposite problem—producing too little energy—because of some kind of variation in her Li-Fraumeni syndrome. She wrote to Hwang, who responded that it could be possible.

It turned out that Twinam’s fatigue problem wasn’t connected to Li-Fraumeni syndrome. But Hwang did find in a battery of tests that Twinam’s calf muscle took a long time to replenish energy. A biochemical analysis found that Twinam’s skin cells were producing too much of a protein called WASF3.

“Zooming inside Twinam’s mitochondria,” the Washington Post explained, “Hwang and colleagues eventually saw something stunning: Like a stick jammed into bicycle spokes, the overabundant protein was literally gumming up the gears of energy production.”

Hwang and another researcher then obtained muscle tissue from chronic fatigue syndrome patients that were part of a different NIH study. Nine out of 14 also had too much WASF3.

“Although the sample size is small,” the Washington Post reports, “the finding suggests that this energy-squashing problem is widespread” in chronic fatigue syndrome, also known as myalgic encephalomyelitis.

Hwang’s laboratory is planning a clinical trial of a new drug for another disease to see whether it will help.

“Amazing findings in medicine are sometimes based on one patient,” Hwang told the Washington Post.

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