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ME/Chronic Fatigue Syndrome Takes Center Stage on First Afternoon of Personalized Medicine World Conference (PMWC) 2017 at Duke

A very moving and informative session on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was held in the mid-afternoon of Day 1 (May 24) at the Personalized Medicine World Conference (PMWC) 2017 at Duke. ME/CFS has been described by NIH Director Francis Collins as “the mysterious illness science has yet to unravel,” and, in this session, three compelling speakers sought to describe the disease, indicate where we are today in terms of research and knowledge of the disease, and suggest where we need to go in the future. The three speakers were session chair Zaher Nahle, PhD, MPA, Chief Scientific Officer and Vice President for Research at the Solve ME/CFS Initiative (SMCI) ( research & advocacy organization; Anthony L. Komaroff (photo), MD, Professor of Medicine, Harvard Medical School, and Senior Physician, Brigham and Women’s Hospital; and John Nicols, MBA, CEO of Codexis (, a protein-engineering company. Mr. Nicols’ wife Marcy, who was in the audience, has had ME/CFS for 25 years. Dr. Komaroff has cared for and studied patients with ME/CFS for 35 years, and is a member of the SMCI Research Advisory Council. Dr. Nahle oversees the research and scientific portfolio at the SMCI that includes the peer-review grant program for external investigators, specialized biobanking, and patient registry platforms, as well as numerous medical education initiatives for patients and healthcare professionals. He also directs a specialized investment program with medical centers, government agencies, and industry partners to spark innovation and accelerate the discovery process in the ME/CFS disease space. Dr. Nahle began the session by expressing his heartfelt gratitude to the PMWC for hosting this session on a very neglected disease. He then briefly outlined what is known about the disease today. He said that ME/CFS affects an estimated 836,000 to 2.5 million people in the United States and that the disease affects an estimated four times as many women as men. 25% of ME/CFS patients are largely bed-bound and the average age of disease onset is 33-34. Dr. Nahle added that an estimated 91% of cases are undiagnosed and almost all diagnosed cases are initially misdiagnosed multiple times. He noted that there are no FDA-approved drugs for ME/CFS and it is currently not a trackable disease by the FDA.

[Editor’s Note: “Seabiscuit” author Laura Hillebrand and actress Morgan Fairchild both have ME/CFS.]

Dr. Nahle said that a 2015 Institute of Medicine Report
( established new clinical criteria for the diagnosis of ME/CFS. This report has moved ME/CFS from a disease that could only be diagnosed by exclusion (that is the elimination of other diseases that had similar symptoms) to a disease that can be diagnosed from a combination of symptoms.

The symptoms typically include various combinations of the following: post-exertional malaise (PEM) (where any moderate exercise or mental effort is followed by the need to spend days or weeks in bed), extreme exhaustion, unremitting pain, non-restorative sleep, brain fog/cognitive impairment, joint pain, inflamed lymph nodes, persistent sore throat, severe headaches, neurological abnormalities, gastrourinary and gastrointestinal complications, irritability and mood swings, and sensitivity to light, sound, odors, chemicals, food, and medications.

The question has long been asked if there are biologic abnormalities underlying ME/CFS and Dr. Nahle’s answer is a definite “Yes,” and Dr. Komaroff would later describe compelling evidence to demonstrate this.

Dr. Nahle noted the many challenges facing ME/CFS patients and advocates today. These include widespread misformation about the disease, a lack of researchers, insignificant funding, lack of FDA-approved drugs, insurance-related difficulties, a hard career path for researchers, and the lack of any feasible biomarkers.

He also cited a severe knowledge gap for the disease that he illustrated with a graph of the growth in numbers of research publications on autism, Alzheimer’s disease, and multiple sclerosis, while the number of publications on ME/CFS has remained low and flat. He also noted that knowledge of the “natural history” of the disease (e.g., data on onset, duration, severity, recovery, deficits, comorbidities, etc.) is still obscure.

He did note a few positive developments, which included a recent increase in scientific and advocacy efforts and increasing efforts of determined stakeholders, including patients and families, advocacy organizations like the SMCI, interested academic entities, and upcoming ME/CFS consortiums and data management centers.

In closing his session-opening remarks, Dr. Nahle sought to dispel three common myths associated with ME/CFS. Myth #1, he said, is that “your blood test came back normal.” He noted that sensitive metabolite analysis by the company Metabolon has revealed serious abnormalities in ME/CFS blood samples. Myth #2 is that “you look normal.” The fact is, he said, that the quality of life for patients with ME/CFS ranks the lowest for any debilitating disease, including diabetes and cancer. Myth #3 is that ME/CFS is caused by depression/anxiety when the facts show that ME/CFS have multiple biological characteristics different from those with depression/anxiety and that depression/anxiety is the most common finding secondary to complex chronic diseases.


Next, Dr. Nahle introduced Dr. Komaroff to describe the substantial evidence for objective biological abnormalities in ME/CFS.

Dr. Komaroff first discussed evidence for central nervous system involvement in ME/CFS for which the data is the most numerous. He cited neuroendocrine (cortisol) findings and deficiencies in cognition (patients often report not thinking as well). He noted that autonomic dysfunction is seen in 30%-80% of patients and that MRIs typically show multiple abnormalities, including reduced white matter and gray matter. He further stated that PET scans often show immune cell activation and neuroinflammation. EEGs, he said, can show distinctive spectral coherence.

He noted that muscle acidosis (lowering of pH) is seen during exercise and that lactic acid is sometimes seen in spinal fluid of ME/CFS patients.

He then discussed the “energy metabolism hypothesis” which maintains that the energy problems seen at the level of the ME/CFS patient may reflect an energy problem at the cellular level, and scores of studies in the literature have investigated this, he said. He noted that the levels of most metabolites are actually reduced in concentration in ME/CFS patients, similar to what is seen in hibernation and also in Dauer state of the C. elegans worm, which is a state of stasis that permits the worm to survive harsh conditions. He also noted defects affecting the energy molecule NADPH and the enzyme pyruvate dehydrogenase that interacts with NADPH.

Dr. Komaroff mentioned ME/CFS-associated immune abnormalities, including chronic activation of CD8+ cells and a down-regulation of natural killer cell function. There is also evidence for auto antibodies targeted against neuronal nervous system cells.

He then discussed the role of infectious agents in the disease, particularly given the oft-reported history of patients saying the ME/CFS came on suddenly, and seemed to have started as a simple flu or cold. Dr. Komaroff said that there is solid evidence that some cases of ME/CFS can, in fact, be triggered by infection. He gave the example of herpes virus that can’t be eliminated and that might cause a low-grade inflammation of the brain that has been posited as being involved in the etiology of ME/CFS.

Dr. Komaroff closed by mentioning the possible role of the microbiome where imbalances have been found in ME/CFS, and the suggestion that bacterial products could get into the circulation, activate systemic immunity, and then pass through the blood-brain barrier to activate the innate immune response in the brain. He suggested that brain-immune system-gut interactions might be involved in ME/CFS.


The next speaker, John Nicols, has a profoundly personal connection with ME/CFS as his wife Marcy has had the disease for 25 years. John, who is the CEO and President of the protein-engineering company Codexis and also the Vice Chair of the SMCI Board of Directors, said that since his wife developed ME/CFS, she has operated at just 20%-50% of her previous activity/energy level. Sometimes, for important events, he said, Marcy can get herself up to 80% for the event, but inevitably pays a huge down-time price afterwards.

John emphasized how widespread ME/CFS actually is, with current estimates making it more prevalent than Parkinson’s disease, HIV/AIDs, Crohn’s disease, and hemophilia—and given the huge estimated percentage (91%) of undiagnosed cases—the likelihood that it is as common as Alzheimer’s.

He noted the importance of trying to identify a relevant target and his belief that the existence of disease subsets is a surety, given the different flavors of symptoms.

He closed by stating that we are “on the cusp of a huge opportunity” in ME/CFS.


Then there was time for discussion with the audience and a woman named Janet, who is an ME/CFS patient, spoke movingly about her situation. She had been a hard-charging engineer who regularly hopped red-eye flights all over the world and she described herself as an extreme Type A personality. But then she developed ME/CFS and everything changed. Her life became quite limited and she became depressed. She lives just 18 miles away from where the PMWC meeting was being held at Duke, but the effort for her to get herself to this session was enormous and would likely take a great toll afterwards. Her story was eye-opening and sad for the audience.

But her story also prompted a very interesting question which was whether over-exerting Type A personalities might somehow be more prone to ME/CFS. Dr. Komaroff responded that in his long experience, he believed that, in fact, such personalities are more highly represented among ME/CFS patients, and furthermore, that patients with ME/CFS frequently report that they were very athletic before they developed ME/CFS.

Dr. Komaroff noted there had been examples in animal models and in race horses, where high levels of activity had been linked to a sudden loss of energy.

Another question was on the overlap of fibromyalgia and ME/CFS. Dr. Komaroff said there is no doubt that the diseases share similarities, and early on, he and others thought they might be the same disease. He noted that there may be some underlying biological differences, but that the diseases are “awfully similar.” He said that three drugs have been approved by the FDA for the treatment of fibromyalgia, but there have been no trials of these drugs in ME/CFS.

Another questioner wondered about the preponderance of women over men with ME/CFS. In response, Dr. Komaroff noted that most autoimmune diseases are more prevalent in women and this is Iikely due to the differences in sex hormones, and that this would lend support to a role for autoimmunity in ME/CFS. He also noted, however, that men, by nature, are less likely to seek help in conditions like ME/CFS so the current sex estimates might be skewed more toward females for that reason.

The session was highly informative, stimulating, and moving, and the need to bring more attention and research to the area of ME/CFS is paramount.


In a related event, the PMWC organizers had arranged a tour of the company Metabolon that took place at the end of the meeting. During this tour, it was mentioned that Metabolon is working with the SMCI to analyze metabolites in ME/CFS patients and that early analysis has demonstrated a lower-than-normal level of molybdenum in ME/CFS patients.

[Solve ME/CFS Initiative] [PMWC 2017 Duke] [BioQuick News story #1 on PMWC 2017 Duke] [BioQuick News story #2 on PMWC 2017 Duke] [BioQuick News story on ME/CFS]