Chronic Fatigue Syndrome (CFS) is a complex and persistent condition that causes extreme fatigue, which doesn’t improve with rest and often worsens with physical activity. This exhaustion is severe enough to interfere with basic daily tasks such as cooking, showering, or getting dressed. In addition to fatigue, people with CFS may experience muscle and joint pain, memory issues, headaches, sleep disturbances, and heightened sensitivity to light or sound.
Despite affecting an estimated 3.3 million people in the United States, according to the Centers for Disease Control and Prevention (CDC), the cause and cure for CFS remain unknown. There is no specific test to diagnose the condition either.
A recent breakthrough in research is providing hope for better understanding and diagnosing CFS. An international team of scientists, led by Cheng, has received funding from the National Institutes of Health to investigate changes at the molecular and cellular levels in muscle tissue. Their goal is to find potential diagnostic tools and treatments for CFS, as well as related conditions like long COVID.
Cheng notes that CFS and long COVID share several symptoms, with muscle pain being one of the most common. Collaborator Tiziana Pietrangelo, a researcher from Università degli Studi “G. d’Annunzio” Chieti – Pescara in Italy, has studied CFS for over a decade. She has discovered that people with CFS show elevated oxidative stress in their muscle tissue, which may explain why their muscles become easily fatigued.
The team is taking a multidisciplinary approach to identify biological markers in muscle tissue that could help diagnose and treat both CFS and long COVID. Pietrangelo will focus on the physiology of skeletal muscle and muscle stem cells, examining how oxidative stress affects their function. Stefano Cagnin, a professor at the University of Padova in Italy, will investigate gene expression in muscle fibers and stem cells, comparing healthy individuals with those suffering from CFS to uncover any molecular changes linked to the condition.
Cheng will examine the electrical activity of skeletal muscle stem cells. Using a technology called broadband electrical sensing, which she co-developed, she will assess characteristics at the cellular level to determine whether a cell is healthy or diseased. “We aim to see if these electrical signatures are specific enough to diagnose the disease,” Cheng says.
Electrical measurements may provide a valuable, cost-effective diagnostic tool, but researchers must first establish how these electrical changes align with molecular abnormalities, a task that other team members are working on.
This research is breaking new ground in several ways. Cheng points out that while previous studies on CFS have looked at various tissues, organs, and systems, her team is among the first to focus specifically on changes in skeletal muscle stem cells. By using a multidisciplinary approach, the team is examining the disease from the molecular, subcellular, and cellular levels.
The long-term goal is to create noninvasive diagnostic tools. Cheng explains, “For example, using an electrode at a specific frequency might allow us to detect abnormal activity in muscle tissue, which could serve as an early indicator of CFS.”
In addition to improving diagnostics, the team hopes to identify the molecular changes driving CFS, potentially opening the door to new therapeutic strategies. These could help reduce oxidative stress and ease symptoms for patients.
Although these advancements are still a long way off, they offer hope for the millions who have struggled with a disease that has long been misunderstood. Cheng emphasizes, “Because CFS was poorly understood, people with the condition were sometimes labeled as lazy or told their symptoms were imagined. The rise of long COVID has made people more aware that these symptoms are real and can follow a viral infection. We’re excited to contribute to this change in perspective and help patients restore their health.”
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