By Erin Allday
A Stanford scientist has developed what could be the first simple blood test for chronic fatigue syndrome, a puzzling and often disabling illness that can take years to diagnose and is still largely misunderstood by mainstream medicine.
The diagnostic test is built on Stanford biochemist Ron Davis’ discovery of a biological marker that distinguishes people with chronic fatigue syndrome from those who are healthy. A description of the biomarker and how it might be used was published Monday in the Proceedings of the National Academy of Sciences.
Assuming his results hold up under further study, the biomarker would be a critical breakthrough in research into the disease. It could make diagnosis of chronic fatigue syndrome much easier and help scientists develop treatments for the illness. And perhaps just as important, the biomarker provides further validation to a disease that has long been brushed aside or even labeled as imaginary.
Davis’ initial study was small, involving only 40 people, and he will need to reproduce his results in much larger trials before he can make the blood test widely available. But patients and scientists in the field said they were enthusiastic about the work so far.
“It’s a major milestone. If it holds up in larger numbers, this could be a transformative advance,” said Robert Naviaux, a genetics professor at UC San Diego who is familiar with the Stanford work but was not involved in the biomarker research.
Chronic fatigue syndrome is thought to affect several million people in the United States, though some reports suggest as many as 90 percent of people who have it have not been diagnosed. The illness can cause severe fatigue, to the point that many people go years without being able to leave their beds and even more are unable to work or have normal social lives.
In addition to the fatigue, symptoms can include chronic pain, problems with memory and concentration, gastrointestinal issues and extreme sensitivity to light, sound and smell. Multiple organ systems can be affected at once. One of the most common effects is known as post-exertional malaise, in which people suffer a severe worsening of symptoms after physical activity.
The disease is formally called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); the former half is a reference to muscle pain associated with inflammation of the nervous system. Though chronic fatigue syndrome is the name most commonly associated with the illness, many patients, doctors and scientists avoid it because they say it makes light of the debilitating nature of the symptoms.
There are no drug treatments for chronic fatigue syndrome. Indeed, Davis hopes that his diagnostic test could help scientists screen for drugs that may alleviate symptoms or cure the disease outright. It would also make it easier for doctors to identify participants for clinical trials, which could speed up research into the cause of the disease and the best ways to treat it.
But the greatest advantage of a diagnostic tool would be for patients, many of whom endure years of frustration and misdiagnosis before finding out what’s wrong with them. Davis’ findings would allow doctors and other providers to diagnose patients within hours based on a blood test, instead of sifting through a subjective array of symptoms.
Jaime Seltzer, who works with the patient advocacy group ME Action, was diagnosed with the syndrome relatively quickly about five years ago because she knew others who had the disease and she recognized the symptoms. But she said many people not only wait years for a diagnosis, but are told in the meantime that their symptoms are in their heads, or that they can improve with exercise.
“And that’s literally the worst advice you can give someone with ME,” Seltzer said, given that post-exertional malaise is such a common symptom of the disease.
“It’s absolutely mind-blowing,” she said. “But a biomarker can and will change that.”
Chronic fatigue syndrome currently is diagnosed through a checklist of symptoms. It’s not a difficult diagnosis, said Maureen Hanson, a professor of molecular biology and genetics at Cornell University who helped develop the list. But many primary care doctors aren’t familiar with the symptoms or still aren’t convinced that the syndrome is real.
“Most people with this disease see four or five physicians before they’re diagnosed,” Hanson said. “If there was a simple blood test to find out, to give an objective piece of data rather than a list of symptoms, that would be helpful to get an accurate diagnosis.”
The biomarker that Davis found is based on how immune cells respond to stress. In his studies, Davis collected blood from participants, then filtered the blood to a sample that contained only immune cells and plasma. He exposed the sample to salt, which is a stress to cells, requiring them to exert energy to retain an appropriate sodium balance.
The stressed sample was then passed through a microchip about the size of a postage stamp, which used electric current to indirectly measure energy exertion. Less exertion meant the cells were having little trouble maintaining the sodium balance, and more exertion meant they were struggling.
Davis found that the test correctly associated high energy expenditure with the 20 participants who were already known to have chronic fatigue syndrome. Blood samples taken from 20 healthy people had notably lower energy exertion.
His research, which cost roughly $200,000, was funded almost entirely by a patient advocacy foundation. And Davis himself is a deeply invested patient advocate — his son has had chronic fatigue syndrome for nearly a decade, and has been bed-bound for almost all that time.
“He’s 35. He’s already lost a good part of his life,” Davis said. “The good news is he’s not getting worse. But I worry about him going downhill and that I won’t figure this out before he dies.”
As excited as he is to have found a biological marker of the disease, “we still need to know exactly what’s causing it,” Davis said. “Then you can know how to treat it. You can cure it.”