Washington – When Amanda Twinam was diagnosed with breast cancer at 28, she began to understand the cause of the fatigue that had plagued her for decades., she underwent a mastectomy and underwent chemotherapy. The chemotherapy drugs made her sick and triggered seizures, forcing her to see a rheumatologist.
In blood tests, experts found markers of autoimmune disease, but none of the possible diagnoses quite fit Amanda’s case. “My main complaint is fatigue; in fact, sometimes that’s my only problem,” Amanda says. When she was in high school, she probably contracted mononucleosis, which left her exhausted for months. “But no one knew how to tell me what to do,” he recalls.
In 2015, after further research, they discovered that Amanda was a carrier of a genetic predisposition to cancer called Li-Fraumeni syndrome.. Soon after, Amanda discovered a second breast cancer and underwent a second mastectomy. But she knew there was something more important…
Today Amanda turns 44 years old. In his 40s, he began to have difficulty walking and standing. She had to quit her full-time job as a lawyer in Albany, New York, and take a part-time job: she couldn’t handle the legal cases she was responsible for, couldn’t raise her young daughter, and couldn’t care for her illness.
“I was a person with diminishing functions. I couldn’t explain what was happening to me, and it was driving me crazy,” Amanda recalled. “The doctors didn’t know what to do with me.” ” so He spent several years trying to understand the causes of his persistent fatigue, neuropathy, muscle weakness and other problems.
Their tireless efforts have led to a new scientific discovery from the National Institutes of Health (NIH) and a series of promising new studies that could help others suffering from chronic fatigue, including those suffering the long-term effects of COVID-19.
“We’re very excited about trying drugs” to treat the problem Amanda identified, said Paul Wang, an NIH researcher who led the study.
Amanda developed warning signs of an unknown chronic illness after developing suspected mononucleosis in high school. She feels like she never fully recovered. An important clue: When I was in college, I didn’t experience an endorphin rush after working out. Instead, “I felt like a rag.”as he told his friends.
During two bouts with breast cancer, Twinam decided to go back to school to get a master’s degree in public health. She wanted to understand what was happening to her by understanding the science of biostatistics. “When I got a 10 on my biology midterm, I was more excited than I was when I passed the final,” he admits.
In 2016, she read an article written by Huang about Li-Fraumeni syndrome, which aroused her interest. The article describes problems with mitochondria, the famous powerhouses of cell biology, the small tube-like structures within cells that generate the energy our bodies use.
Huang’s lab found that the mitochondria of people with this cancer-susceptible syndrome produce excess energy, which cancer cells use to multiply and metastasize. Amanda began to wonder if her unique form of Li-Fraumeni syndrome might be causing the opposite problem: a lack of energy.
Amanda sent a message to Huang The title proved crucial: “I read with interest your recent article on the inhibition of mitochondrial respiration in a mouse model of Li-Fraumeni syndrome.”
Huang, who runs the lab at the National Heart, Lung, and Blood Institute, responded the next day: “Yes, I agree with you that Li-Fraumeni syndrome may alter your metabolism and cause the following symptoms: Fatigue.
Huang was wrong: Amanda’s lack of energy had nothing to do with Li-Fraumeni syndrome. But to come to this conclusion, Huang and his colleagues spent years of laboratory work, including developing genetically modified “Amanda mice.”.
“Amanda Twinum’s presence was a challenge,” Huang said. So we started digging. “
In 2017, Huang took Amanda to Bethesda Hospital. In a series of studies conducted on her, a strange result emerged: After a brief period of physical activity, Amanda’s calf muscles took a long time to replenish energy-carrying molecules. In other patients with Li-Fraumeni syndrome, the molecule regenerated in an average of 35 seconds. Amanda took more than twice as long: 80 seconds. “We’ve never seen delays like this,” Huang said.
Out of confusion, he brought Amanda’s brother and father to Maryland because both were carriers of the Li-Fraumeni syndrome gene. But in the power generation test, both showed a rapid energy rebound that was different from hers. Neither of them complained of severe fatigue.
The exception remains Amanda.
Huang now has compelling evidence that Amanda’s energy problems—both at a cellular and functional level—are caused by something else. But what?
Around the same time, in 2017, Huang accidentally received another email. NIH researcher Brian Walitt, Ph.D. I heard Huang was studying energy production within mitochondria.
Wallett is interested in the topic because he is organizing an in-depth study of a small number of patients diagnosed with chronic fatigue syndrome admitted to an NIH research hospital. Also called myalgic encephalomyelitis or ME/CFS.
This information piqued Mr. Huang’s curiosity: What if Amanda, a patient with an unusual cancer syndrome, also suffered from a disease like ME/CFS that causes chronic fatigue?
He then began thorough biochemical research. He found that cells taken from Amanda’s skin seemed to produce excess amounts of a protein called WASF3. While studying the inside of Amanda’s mitochondria, Huang and his colleagues finally saw something surprising: a stick wedged between the spokes of a bicycle wheel. Excess protein can actually interfere with the gears of energy production.
Mitochondria produce energy through the process of cellular respiration, which converts oxygen and glucose into energy-carrying molecules. At the center of this chemical chain reaction is a biochemical giant called the mitochondrial supercomplex.
Amanda’s overproduction of protein severely clogged this supercomplex. “It actually brought everything to a crashing halt,” Huang said.
Extensive laboratory work confirmed and extended this finding. In cell culture dishes, excess WASF3 reduces cellular energy production, while inhibiting cell proliferation produces more energy. Like Amanda, the mice that produced too much protein quickly pooped what they ate and spent about half the time on the wheel as normal mice.
Finally, a chance opportunity expanded Hwang’s research from a single patient to an entire patient population: He obtained muscle tissue from Walitt’s patients with chronic fatigue (ME/CFS).
Nine of the 14 people had similar levels of WASF3 to Amanda, and on average, their levels of the protein were higher than those of healthy volunteers. Although the sample size was small, the findings suggest that suppressed energy production is prevalent in ME/CFS patients.
The investigation that began with Amanda’s case culminated in August with an article by Huang and colleagues in The New York Times. science magazine Proceedings of the National Academy of Sciences. Scientists working in the small field of ME/CFS are excited about the discovery, which suggests a potential and much-needed treatment strategy.
ME/CFS is common—2.5 million Americans have the disease, according to a 2015 report from the Institute of Medicine—but it’s also often misunderstood.
Research in this area has been poorly funded, and diagnosis is often delayed or never reached at all. Studies show that up to half of patients with long-term COVID-19 infection meet this diagnosis, and the epidemic has caused a sharp increase in the number of ME/CFS patients. There is no blood test to identify the disease, and there is no Food and Drug Administration-approved treatment, let alone a cure. Approximately 25% of people with ME/CFS are bedridden.
“What motivates me most right now is developing treatments for this disease,” Huang said. His small lab of four scientists is planning a clinical trial of a recently launched drug to treat another disease.
“In medicine, the most surprising discoveries sometimes come from individual patient cases,” the scientist said.
As for Amanda, who has been feeling unwell for decades without a proper diagnosis, she believes her personal story has finally been legitimized and featured in a major scientific journal..
“There’s a big difference between cancer and chronic fatigue syndrome, and her rheumatologist eventually added that diagnosis to her medical history,” Amanda said. When you have cancer, everyone believes you, but No one believes you when you say you have chronic fatigue syndrome. Now I can finally say: This is not psychological, I am not a storyteller! “Now we have a scientific explanation.”
(Translated by Jaime Alambide)