Chronic fatigue syndrome is arguably one of the most misunderstood conditions in medicine. Between 1 million and 4 million people suffer from the disabling disorder, yet it's often not recognized by physicians as a real disease.
Jose Montoya, MD, a professor of infectious disease, is a leading specialist in the field. He has been treating patients for more than a decade and has been studying the underlying mechanisms of the disease, which is also referred to as myalgic encephalomyelitis, or ME/CFS.
Recently, Montoya and Mark Davis, PhD, director of Stanford's Institute for Immunity, Transplantation and Infection, published a study linking the disease to variations in 17 immune system proteins, suggesting that inflammation is a powerful driver of the condition. The findings could help in the diagnosis and treatment of this mysterious disorder. Montoya was interviewed by Stanford Medicine News about the latest research.
Q: You have worked with many CFS patients over the years. How does the disease impact their lives?
Montoya: It devastates their lives. It ruins their occupational, educational, social and productive activities. It turns upside down any hopes and happiness.
Q: What did you and your colleagues find in the latest study?
About seven years ago, we decided to design a study to answer the question of what the disease is. We knew we had to get a study with a significant sample size. We consulted with statisticians, and with their recommendation we came up with a sample size of 200 patients and 400 healthy controls. We analyzed their blood samples and found that there were 17 cytokines that track the severity of the illness and the patient's symptoms. Of these, 13 are pro-inflammatory. A cytokine is a small protein that the immune system uses to communicate with other cells. These cytokines can be protective, but they can also be harmful. That's where the issue is — it's a double-edged sword.
Q: What are the implications of the study?
Montoya: This is telling the world that we have finally a biological correlate for these patients' symptoms. These patients are not crazy. Our findings validate their symptoms — that their illness is real and has a biological basis. Now we know that this is something real, ingrained in the biology of the body and the immune system, that explains why these patients are so sick, we could end up with a blood test, but equally or more exciting, we can find drugs to conquer the disease.
Q: As someone who has worked in this field for so long, it must be very gratifying to have found some clear biological underpinnings for this mysterious illness.
Montoya: I was ecstatic. It was a sunny morning in California. We have the routine of meeting weekly to review new results. When I saw that, that was like a eureka moment. It was clear to me that morning that we had something big in our hands. We were able to measure something in the blood, and it was tracking the symptoms.
Q: How might the study impact treatment?
Montoya: In a major way, possibly. People had suspected inflammation as the main driver of the disease, but the conventional tests had been normal. We now have other ways to measure inflammation that were not available five years ago, thanks to the efforts of Mark Davis and others. Now we can use those techniques to look for drugs and therapies that treat that inflammation.
Q: Could this lead to the development of a diagnostic test, and if so, how long might that take?
Montoya: That is something we are working on — a panel of tests that will tell that this patient unquestionably has the disease. Taking into account everything that goes on in the laboratory, I expect that to take one and a half to two years.
Q: What has been the response to the study?
Montoya: It's been huge — more than I anticipated. We have been receiving hundreds of emails a weekfrom patients, patient advocates, media and others. The one thing I was not expecting was the press coverage. It went truly wild. I don't like the spotlight. But that gave me the hope that these reports might be seen by groups working on drugs that precisely treat the inflammation. We are starting to see that. We are getting emails from pharmaceutical companies that say they have compounds that may counteract that inflammation. That would be exciting because that could lead to the first-ever targeted treatment for this disease.
We knew scientifically that this was a significant leap forward, but the important thing is, can we find that drug? There are other inflammatory diseases that have treatments that are effective, like lupus and rheumatoid arthritis. So now that the study has established it's inflammatory, we can look for those drugs that treat inflammation. I could die happy if I knew that was the door that was opened.