For decades sufferers of Myalgic Encephalomyelitis (ME), commonly known as Chronic Fatigue Syndrome (CFS), were labelled as “depressed” or “told that the symptoms were in their head”. But two four-year studies by Otago’s Emeritus Professor Warren Tate, and Dr Aniruddha Chatterjee, published recently in the journals Clinical Epigenetics and the Journal of Translational Medicine, have proved otherwise.
“This current research is the culmination of a range of molecular studies on a small group of very well clinically characterised group of patients using the principles of personalised medicine. We have found many changes in important physiological and biochemical pathways and systems compared with healthy controls. These changes can explain the diverse symptoms experienced, and the ongoing disease course,” Professor Tate says.
“They are definitely organic rather than psychological changes and are indicative of a complex disease involving many physiological systems of the body.
“Our studies have shown unequivocally this is not a psychosomatic illness.”
ME/CFS is a poorly understood lifelong debilitating disease estimated to affect between one per cent and seven per cent of the world’s population, he says.
The symptoms include severe fatigue, post-exertional malaise, cognitive and sleep dysfunctions and additional symptoms that are often so severe they leave patients house or bed bound. About 75 per cent of cases move with time to a chronic phase of the illness that is still debilitating. The absence of effective therapies means it remains with them for life.
The two recently published studies, run simultaneously, aimed to explain the pervasive lowered energy that is a core symptom of the disease, why patients suffer so many effects related to the brain and nervous system, and why sufferers seem to be in a “state of hibernation” with a lower rate of biochemical activity.
They found the “powerhouse of the cell”, the mitochondrion – responsible for making most of the energy required for our functions – has many of its components produced in higher amounts, and some in lower amounts in ME/CFS patients.
“These results suggest that this part of the cell was in a state of not being able to produce enough energy and was trying to compensate for that by producing more of the factory components. This speaks to a lowered energy in patients and can contribute to the pervasive fatigue.”
To try to explain why CFS patients might be functioning “rather like a hibernating animal”, researchers examined in detail the dynamic DNA code – called the epigenetic code. It determines, through adding and taking off chemical methylation tags on the DNA, the activity of all the body’s genes.
Professor Tate says he is privileged to collaborate with Dr Chatterjee – a world leading expert in epigenetic analysis.
“By using cutting edge sequencing technology for analysis, we discovered changes in the dynamic epigenetic code that could explain why ME/CFS patients function at a much lower level than their healthy peers. We also found changes that explain many of the neurological symptoms as the study highlighted genes involved in a part of the brain called the hypothalamus and subsequently a pathway that leads to the production of the body’s main stress hormone, cortisol. Low cortisol in CFS patients can lead also to low energy, and fatigue.”
For Professor Tate, the research is deeply personal and the findings the culmination of long experience with the disease.
“Following a bout of glandular fever, my then 14-year-old daughter had a sudden dramatic decline in health that today we know resulted from the onset of ME/CFS. As a family we have lived with this ongoing illness now for 30 years.
“From the beginning I became aware that this disease was not well recognised nor understood by health practitioners within mainstream medicine, and was even denied as a real physical illness by some. However, from both the origins, personal observations of my daughter’s symptoms and course of the illness, I was convinced that ME/CFS had a biological basis and was not psychologically or socially based as some were claiming. I embarked on research in the last decade with this conviction to find evidence in patients of the underlying biology,” he says.
“With my family experience of ME/CFS, I have a passion to improve the circumstances of those affected with this illness by explaining their debilitating symptoms, and ultimately have a hope of finding therapeutic avenues that might mitigate the severity of their illness.”
Being an “unexplained” illness with diverse opinions among the medical community about its nature, ME/CFS research has been hard to fund from mainstream investments agencies. Most of the funding for this research came from ME/CFS-affected families.
“Affected families have had to search for options to help with their condition with little effective help from health and social services in New Zealand and elsewhere,” Professor Tate says.
“New Zealand patients, and those who have enthusiastically agreed to be part of our study groups, have shown much gratitude that attention is being paid to understand their condition with some hope for future improvement of their life-long journey with the illness.
“Our providing information on the extent of the disturbed biochemistry and physiology in ME/CFS patients is an important step not only in understanding the disease but also for designing smart therapeutic options to alleviate the symptoms. Ultimately the goal is trying to find strategies to reverse what is a life-long condition. The canvass of this disease is no longer blank.”
For more information, contact:
Emeritus Professor Warren Tate
Department of Biochemistry
University of Otago
Mobile 021 392 314
Dr Aniruddha Chatterjee
Department of Pathology
University of Otago
Phone 03 479 7172
University of Otago
Phone 03 479 4969
Mobile 021 279 4969