New research centre for ME at Uppsala University
18 June 2019
Today, between 10,000 and 40,000 people in Sweden are suffering from myalgic encephalomyelitis or ME. In the search for a cure for the complex disease, a new research centre is being built up in Uppsala under the leadership of Professor Jonas Bergquist. “In the last three years, we have gained a molecular understanding of the disease that have previously only been seen as a syndrome or a collection of unclear symptoms.”
There is currently no cure for the disease previously referred to as chronic fatigue syndrome, CFS. The name alludes to the victims' testimonies of overwhelming fatigue, something that was believed to be due to burnout syndrome. But as other diseases have been excluded and it has been found that the patients' condition does not improve with rest, the picture of ME has been revised.
One who has researched the reasons behind the enigmatic disease for over 10 years is Jonas Bergquist, professor of analytical chemistry and neurochemistry at the Biomedical Centre at Uppsala University. His research team investigates whether some biomarkers in ME patients' cerebrospinal fluid can detect on-going neuroinflammation.
“Our research shows that it is an interesting process that we can measure in the pattern of protein change. Although the inflammatory onset is small, the system appears to lose the ability to regain energy and it is also possible to detect an on-going degradation of the nervous system.”
Although there are several promising leads, there are today no established biomarkers for ME. Today there are hundreds of markers studied through blood tests or by samples of the spinal fluid, so called cerebrospinal fluid. In addition, the disease is not revealed by one but several biomarkers, and the other symptoms must also be weighed in, according to Jonas Bergquist.
The involvement of hormones is investigated
He believes another piece of the puzzle is in the regulation of neurosteroids, as a majority of ME patients have lowered levels of these.
“We have now found significant changes on one of the key steroids found in our biochemical cascade of hormones. There are of course other patient groups who have problems with hormone regulation. But if we compare with age- and gender matched controls, it turns out that ME patients have a significant decrease for this particular steroid. Currently, an extended study is underway to confirm the findings.”
According to Jonas Bergquist, biomarkers will be an important part of the understanding and acceptance of the disease. In the past, it was not believed that multiple sclerosis (MS) was a neurological autoimmune disease but once the clear biomarker evidence was obtained, the disease was accepted. Today, there are also good treatment options for MS.
“How far away we are from a diagnostic test for ME through biomarkers is difficult to answer. Perhaps we can understand the phenomenon better within the next few years - why the patient gets neuroinflammation, why the energy loss arises and if there are genetic factors that play a role.”
Contacted by patients and relatives
In mid-May, Professor Jonas Bergquist participated in "Malou After Ten" on TV4. The entire program was devoted to ME with researchers and patients in the studio. Afterwards, Jonas Bergquist received a large amount of e-mails and phone calls.
“It is mainly patients and relatives who express their great appreciation for the research we do. They often want to participate in upcoming research studies or ask for advice on different things. It is also researchers who are interested in collaboration that contact us, but we really want to conduct research in close collaboration with the patients in order to hopefully achieve results faster.”
Jonas Bergquist has also described the research situation around ME in the recently published autobiography by writer Karin Alvtegen: Invisibly ill - while life passes by. Co-written with journalist Karin Thunberg, the book describes the nature of the disease and how it affects both patients and relatives.
Given the history of ignorance and misunderstandings that have prevailed around the disease, great hopes are attached to the research. And, according to Jonas Bergquist, significant progress has been made over the past three years about a disease that the health care system has known about for at least 70 years.
“We have now gained a molecular understanding of the disease that have previously only been seen as symptoms. One can start to tie biology, chemistry, neurophysiology and neurochemistry to these symptoms, which is a very important and an important introductory step before a potential treatment and possibly a cure.”
New centre enables close patient collaboration
Uppsala University's new research centre around ME will be the third in the world after the universities in Stanford and Harvard. All projects are funded by the Open Medicine Foundation, a research foundation in the United States based on private donations. In Uppsala, the funds will initially be used for a doctoral student in analytical chemistry, the first in Sweden that has a focus on biomarker research within ME. The centre therefore starts on a small scale and develops from the existing research solution.
“In addition, other research groups and the already existing specialist clinics for ME in Sweden will be associated with us, says Jonas Bergquist. “The focus will be on care, diagnostics, sampling, collection of samples and biochemical analyses.”
“In parallel with our own studies, we also place great importance on validating the research of others. ME patients are not a homogeneous group and it is important to identify the different subgroups that appear to exist. Distinguishing them provides greater opportunities to find biochemical markers that explain the mechanisms underlying the symptoms.”
A future hope is further funding from more sources. Previously, the classification of the disease has complicated the funding situation, whether it be a neurological disease, an infectious disease or a psychiatric disease. The latter can now be excluded, says Jonas Bergquist, but the uncertainty has contributed to the disease falling between the chairs of potential financiers.
With more funding, more people could be employed, including research nurses for further sample collection.
“Finding patients is not a problem, there are many patients asking for help. Collecting samples, however, is a cumbersome procedure that must be carried out according to very strict protocols in order for the analysis response to be able to be interpreted. In some cases, one must also go home to the patient and collect the samples because they are so severely ill that they cannot get to the clinic.”
Another group of patients that Jonas Bergquist wants to focus on in Uppsala, is a somewhat forgotten group - those who have actually recovered.
“They usually disappear from the care, they are not followed up and are forgotten about. After the TV- program, several former patients contacted me and told me that they had been diagnosed with ME for a number of years, but then recovered and were able to go back to more or less a normal life. One would like to study such a group more closely. There may be samples collected and stored in the biobanks, which can be compared with the person's samples today.”
ME/CFS is classified as a neurological disease by WHO and is often referred to as neuroimmunological. It is a complex multisystem disease in which the nervous system, immune defence and energy production are affected.
ME/CFS affects 0.1-0.4 per cent of the population, which corresponds to 10 000-40 000 in Sweden.
The diagnosis is made according to the Canada criteria. The characteristic of the disease is a breaking and significantly disabling energy shortage and effort-induced deterioration (Post-Exertional Malaise, PEM). PEM means that the condition worsens after both physical and mental activity that exceeds the body's individual tolerance level and can lead to prolonged deterioration. Common significant symptoms that the ME-affected also live with are flu symptoms with a sense of fever, head and muscle pain, memory and concentration difficulties, impressive sensitivity and orthostatic intolerance.
ME/CFS occurs in various severity of functional and activity impairment. Approximately 25 percent of patients are bound to their homes or bedridden. The disease is considered chronic when only a few regain their previous functional ability. Children and adolescents generally have better prognosis. Biomedical research provides hope for future effective treatments.