Ronald Tompkins is also Chief Medical Officer of the Open Medicine Foundation and co-director of the OMF-sponsored ME/CFS Collaboration at the Harvard-Affiliated Hospitals, Harvard Medical School, Massachusetts General Hospital.
He has had 450 research papers published in medical and engineering journals. His research in genomics and proteomics role in inflammation and metabolism underscore his research into the underlying mechanisms of ME/CFS.
Professor Tompkins took time out from his busy schedule to be interviewed about his research into ME and other issues related to the illness.
How did you get involved in the field of ME research?
As a trauma surgeon and investigator, I have been interested in inflammation and metabolism my entire career. As I became exposed to patients with ME/CFS, it became clear to me that both these phenomena were heavily involved and active in the disease. I was impressed at the number of previously very active young people whose lives were being destroyed by the effects of inflammation and abnormalities in metabolism. My longtime colleague and friend, Ron Davis introduced me to the disease and I recognized how poorly the medical profession was handling this disease and I then became very interested. I got involved with the Open Medicine Foundation and have become committed.
Can you tell us about some of your current research into ME?
There are many investigators at Mass General Hospital (MGH), Brigham & Women’s Hospital (BWH), and Beth Israel Deaconess Medical Center (BIDMC), all Harvard-affiliated Hospital, who are actively engaged in ME research. At MGH, we are interested in the “neuroinflammation” that involves the brain and contributes to the “brain fog”, circadian rhythm, dysautonomia, and other problems with ME. We are also experienced in skeletal muscle structure and function that might contribute to the post-exertional malaise, and lastly, we are also very actively involved to better understand the small fiber neuropathy (SFN) that contributes to the dysautonomia and pain involved with ME. At the BWH, there are active studies about the fatigue component particularly as it relates to the cardio-pulmonary origins of the disease. There is also tremendous interest in the SFN component of ME. Lastly, at BIDMC, investigators experienced in sleep research are interested to better understand why sleep is so problematic and non-refreshing.
There is ample evidence to suggest that low grade inflammation of the brain is present in people with ME/CFS. Does this inflammation get worse when a persons symptoms flare up? To what degree is this inflammation responsible for the symptoms that people with ME/CFS suffer from?
Certainly the neuroinflammation is an important component in ME. At MGH, we have two world class neuroimaging facilities at the Martinos Center and the Gordon Center. At the Martinos center, we have multiple dual instruments (MR/PET imaging instruments) that are critical to study neuroinflammation with high precision. We are actively engaged in such studies to begin to answer your questions. Right now, we have suspicions but we would hope to soon have answers for your questions. More importantly over time, hopefully we might have treatments that might begin to attenuate or mitigate these effects.
Can you explain what preload failure (PLF) is? How might PLF affect the symptoms of people with ME/CFS?
Dr. Systrom has described a finding of preload failure (PLF). There are two forms (high flow and low flow). Please see a further description of this on our website (endmecfs.mgh.harvard.edu). Preload heart failure means that at peak exercise, the heart fails to meet the cardiovascular needs imposed by the exercise. Preload means that basically, the venous return was not augmented to the extent that normally occurs to generate the increased cardiac output required by the higher demand of the exercise. In healthy volunteers, the venous return to the heart increases with exercise and this generally comes from a reduced compliance or capacitance in large veins, which is most often facilitated by increase sympathetic tone. It does not appear to happen naturally in ME in the low flow phenotype of PLF.
The high flow phenotype, theoretically there might be two types: those with a peripheral shunt and those with poor extraction. These are two different etiologies and would likely require two different treatment strategies. We would love to begin to study both these possibilities and we seek funding to do so.
One of the central features of ME/CFS is post exertion malaise. Do scientists have any idea why people with ME/CFS have a delayed recovery from physical/mental activity?
We do not. We do know a tremendous amount about how skeletal muscle responds to significant stress in the case of severe injury. It is possible that the stress response in ME is maladaptive and expresses similar abnormalities that are seen with serious injury. We are actively pursuing this possibility. It could simply be that the reparative mechanisms are delayed in ME and there might be targets that we can identify to develop drug treatments to correct these abnormalities.
What can public health authorities do to help improve the life outcomes for people with ME/CFS?
First to recognize ME as a disease and create a priority to better understand the disease and the magnitude of the impact of this disease. Secondly, support activities to develop outcome measures to more accurately determine the impact of this disease on an individual’s quality of life and to collect these data to derive a societal level of impact of the disease. None of this is occurring at the moment.
