Lizzie Mooney is 12 years old. She is tall for her age with long blond hair. She likes to wear Chicago Bears pajama bottoms and a hoodie. She’s funny, making up games and teasing her siblings.
Lizzie excels in reading and math. She spends time crafting and watches science shows with her parents at night. But it’s hard for her to make it downstairs to the TV room. She can’t go to school. In fact, she might only leave her house once a week.
For the past three years, Lizzie has been sick.
The government estimates that as many as 1 million to 2.5 million Americans have the same disease as Lizzie: myalgic encephalomyelitis, or ME. Despite these numbers, you probably haven’t heard of ME. What you might have heard of instead is chronic fatigue syndrome, or CFS. This euphemism for ME conjures an image of someone who just doesn’t feel like getting out of bed.
For many ME patients, getting out of bed would be the highlight of their week or month. About 25 percent of patients are housebound, in rooms with the blinds drawn and noises muffled. Patients’ bodies are sensitive to all kinds of stimulation; they suffer from gastrointestinal problems, inability to sleep, chronic pain and the disease’s trademarks: cognitive dysfunction and post-exertional malaise, or PEM. Many patients describe PEM as a crash. Something as simple as a short walk can severely worsen a patient’s symptoms, leaving them bedridden, unable to recover, for weeks or months. There’s no telling how long the crash will last. Imagine having to decide between taking a shower and making yourself lunch. It could be your only activity for the week. Patients with ME have reported lower quality-of-life scores than patients with terminal cancer and heart disease.
Yet federal funding for ME research remains at a fraction of what is spent on each of these. In fact, research funding for ME remains less than what the government spends on headaches or hay fever. Multiple sclerosis funding is 12 times the funding for ME, but an estimated 400,000 patients in the U.S. have MS, fewer than half the number who have ME even according to the most conservative estimate.
When Lizzie got sick, her mother, Amy Mooney, took her to their primary care physician, who diagnosed Lizzie with a mononucleosislike illness. Lizzie spent the next four months in bed. Mooney took her to infectious disease doctors, rheumatologists, neurologists and gastroenterologists, but no one could make a diagnosis.
“The most painful moment was when an infectious disease doctor took me into the hallway,” Amy Mooney said. “He said, ‘Congratulations. Her blood work is completely normal. Nothing is wrong with her.’ In the patient room, they were asking Lizzie if we have a healthy family life: Do we have abusive family situations?
Are we going through a divorce?
“The physician at the pediatric hospital wrote a note to the school saying it was safe for her to go to school,” Mooney said. “‘Get her back to school. Kids with cancer go to school.’”
Lizzie hasn’t been to school since she was nine. She works at home with a private tutor when she can.
For decades, the search for pathogenic underpinnings for ME came up empty, and the disease was attributed to psychological causes. Stigma, skepticism and limited funding have fueled what advocates characterize as a vicious cycle that’s left a big hole in ME research. But advances in our understanding of the gut microbiome, cell-mediated immunity, mitochondrial dysfunction and dozens of other variables may open the door to new approaches to understanding and treating the disease.
While ME’s existence is no longer controversial, within the ME community, federal funding for ME research is. In recent years, the National Institutes of Health has spent between $5 million and $8 million a year on ME research. In 2017, the NIH earmarked $7 million for a first-time ME research collaboration of four centers. But some advocates say the government should be dedicating more than 50 times that amount.
Steps in the right direction?
Among those advocates is journalist Hillary Johnson, who says billions of dollars would be an appropriate figure.
Johnson spent almost a decade during the 1980s and 1990s researching the befuddling lack of interest in ME by government entities such as the Centers for Disease Control and Prevention and the NIH. She compiled her findings into a book, “Osler’s Web.”
In her book, Johnson chronicles the ’80s as a time when the CDC actively buried ME research and funding. She also casts Stephen Straus, a senior investigator in the Laboratory of Clinical Investigation at the NIH’s National Institute of Allergy and Infectious Diseases, or NIAID, from 1991 to 1999, as the chief villain. Straus published a number of studies on ME, some of which psychologized the disease. Straus went on to become the first director of the National Center for Complementary and Alternative Medicine. When he died in 2007, he was warmly remembered by his colleagues and was lauded by the NIH for what was then still called chronic fatigue research.
Joseph Breen is the current chief of the immunoregulation section in the Division of Allergy, Immunology and Transplantation at the NIAID. “Fortunately, perspectives about the disease have changed,” Breen said. “Researchers now have the tools to explore possible etiologies of ME/CFS and future studies should be revealing, especially those with larger cohorts, initiated early after disease onset and with longitudinal follow-up.”
The NIH announcement in September of four grants totaling more than $7 million for fiscal year 2017, and continuing for the next five years, signifies a step in official ME recognition. The new NIH grants will support three collaborative research centers and a data-management coordinating center for ME research. One grant is going to researchers at Cornell University led by principal investigator and American Society for Biochemistry and Molecular Biology member Maureen Hanson. A 2016 study in Hanson’s lab found that ME patients’ microbiomes have significantly lower microbial diversity and a higher incidence of pro-inflammatory species than in healthy controls.
Hanson’s work also branches into fatty acid and lipid metabolism. Her lab produced a 2017 paper on a study that found significant disturbances in numerous fatty acid and amino acid metabolism pathways. Levels of energy-related metabolites, such as ATP and ADP, were significantly lower in ME patients. Acetylcarnosine and taurine, important to muscle tissues, also were less abundant. Hanson and her colleagues at Cornell will use the new NIH grant to study post-exertional malaise using neuroimaging, metabolomics and single-cell RNA sequencing.
The researchers will take blood samples before and after the study participants ride stationary bicycles on two consecutive days.
To determine why ME patients usually can’t replicate their initial performances, the researchers will search their blood samples for biomarkers.
Hanson’s specific role in the project will be to study extracellular vesicles, which transport materials between cells. In healthy people, exercise induces release of these vesicles, which may mediate the beneficial effects of physical activity.
“This is going to be an important study to carry out — at the time we wrote our proposal, there were no published studies about extracellular vesicles in ME,” Hanson said.
If patients can fall into severe PEM after even basic activities, how could Hanson’s team find ME patients willing to do two days of exercise testing?
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