German Researcher Steps Up
Carmen Scheibenbogen MD is another sign that the ME/CFS field is slowly but surely hopefully catching on. Scheibenbogen is relatively new to this field, but she’s not new to medical research. A trained oncologist and hematologist as well as a physician and Professor of Immunology in Berlin, her research resume includes over 150 publications dating back 25 years.
Dr Scheibenbogen has identified what she believes is an autoimmune subset in ME/CFS. (Image from Invest in ME)
In short, she’s a respected and established researcher, and one from Germany to boot. (I can’t remember the last German researcher to take on ME/CFS.) Her path to ME/CFS has not been an easy one. Germany hardly acknowledges ME/CFS as a disease, and doesn’t fund ME/CFS research – if I’m reading her right, there is apparently literally no avenue to apply for ME/CFS research funding there.
Yet she’s very quickly become one of our most prolific researchers. Over the past four years her team has published no less than seven papers, has won two Ramsay Awards, and played a central role in the development of the new European Research collaboration, EUROMENE. Her biosketch lists CFS/ME, Immunodeficiency, and Cancer Immunology as her main research interests.
Scheibenbogen’s first ME/CFS publication In 2014 found ME/CFS patients mounting a feeble response to Epstein-Barr virus (EBV) . The reduced response to EBV reactivation could help explain the ups and downs seen, particularly during stressful situations.
In 2016, figuring that when Rituximab worked in ME/CFS it probably did so by whacking antibody producing B-cells, her group examined antibodies against a variety of receptors that affect blood flow, the autonomic nervous system, etc. They found that about 30% of ME/CFS patients in a large study (n=293) had increased levels of antibodies to adrenergic (B2) and/or muscarinic M3/M4 acetylcholine receptors (M3/M4).
That suggested that the immune systems of a significant subset of ME/CFS patients might be attacking the receptors on cells which regulate blood flow, lung functioning, muscle contractions and attention. Furthermore, the finding (a “remarkable” one they said) that the antibody levels of two receptors correlated with a host of immune factors (immunoglobulin levels, T cell activation, elevated ANA, TPO antibodies) suggested that this subset of ME/CFS patients are suffering from an autoimmune disease. Scheibenbogen has suggested that the kind of ME/CFS you have may be dependent on the kind of autoantibodies present in your system.
See Bad Bacteria, Brainstem Abnormalities and Progress with Rituximab: the Invest in ME Conference
Similar antibody findings have been found in a range of diseases (postural tachycardia, regional pain syndrome, Alzheimer’s, Sjogren’s syndrome, asthma) some of which have been associated with ME/CFS.
They also noted that immunoadsorption factors that are able to mop up these antibodies had proven to be helpful in some diseases. Two years later they put that idea to the test.
Possible Autoimmune Treatment
PLoS One. 2018 Mar 15;13(3):e0193672. doi: 10.1371/journal.pone.0193672. eCollection 2018. Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. Scheibenbogen C1,2, Loebel M1, Freitag H1, Krueger A3, Bauer S1, Antelmann M1, Doehner W4, Scherbakov N4, Heidecke H5, Reinke P2,3, Volk HD1,2, Grabowski P1.
They used a blood purification technique called immunoadsorption to eliminate the B2 antibodies from people with ME/CFS who’d had a post-infectious onset and high B2 antibody levels. Immunoadsorption (IA) was given five times over seven days to completely wash out the antibodies. Over the next six months the participants’ symptoms, muscle strength, endothelial functioning and immune factors were watched.
Findings
Significant improvement eventually followed by a relapse was the order of the day. One patient who could barely walk prior to the treatment was able to walk several hundred yards at the end of the IA process. She completely recovered for seven weeks and then relapsed. Another patient improved enough to go back to work but then relapsed. Five patients who improved started to relapse by the end of the six months. Three patients – a good third of the study – felt significant improvements in fatigue lasting at least 12 months.
The levels of all four antibodies (B1, B2, M3 and M4) declined after the treatment in all 9 participants. These are good results which are hampered by the small sample size and lack of a placebo control. Through our experiences with Rituximab, Synergy and Mirogabalin we’ve learned how little to trust early results. Still, research has to start somewhere and the results thus far present hope for a significant subset of ME/CFS patients.
Present and Future Work
Ramsay Award Standout
The Solve ME/CFS Initiative (SMCI) provides funding to five or so researchers every year in its Ramsay Awards. The Awards are quite competitive with SMCI receiving far more applications than it can fund, but over the past two years the Scheibenbogen group has won two – the only group to do so.
2016 Award
Citing “ample evidence of an autoimmune pathomechanism” the Scheibenbogen team will be digging into the genetics of their “autoimmune subset”. They’ll be determining if genetic abnormalities in the enzymes or transcription factor that turn on the autoimmune processes are present. They’re also analyzing the immune cells (dendritic cells, regulatory B-cells) known to produce autoimmune responses.
This is one of the first times that I’m aware of that a research group has targeted a subset and dug deeper into it. Scheibenbogen’s focus is clearly good news for people in that subset but it’s also good news for people outside of it. If she’s found a robust subset then it needs to be peeled off from other ME/CFS patients because it’s undoubtedly confounding study results for those patients.
2017 Award
The 2017 Ramsay Award will determine if T-cells and monocytes are up to the task in ME/CFS. We know that NK and probably T-cells are laggards in ME/CFS patients’ immune systems, but other immune cells are largely untested.
Following on recent findings of impairments in energy production, the Scheibenbogen group is going to determine if T-cells and monocytes have the energy to spring into action when needed. Immune cells are mostly quiescent until they come across a pathogen, at which point they’re required to rev up their engines and explode into action. If they don’t have the energy to “explode” they’ll have difficulty fighting off bugs.
If I have it right, they’re also going to stimulate cells using adrenergic and acetylcholinergic factors to see if they affect their metabolism or energy production. Given the role these factors appear to play in the deranged stress response found in ME/CFS, finding a metabolic tie-in would be exciting indeed.
Simmaron Scheibenbogen Collaboration Underway
The Simmaron Research Foundation is also working with Dr. Scheibenbogen to identify the subset of Dr. Peterson’s patients who fit the autoimmune profile, and to further characterize the subset from a clinical perspective.
A Leader
Over the past five years Scheibenbogen has become deeply immersed in ME/CFS. She was the lead author of a paper on the EUROMENE network, which contains researchers and clinicians from 17 European countries. Euromene was accepted into the COST (Cooperation in Science and Technology) framework which was established by the European Union to support collaboration in scientific endeavors. While COST does not fund research studies, it does fund networks and provides networking possibilities across the European Union.
EUROMENE members
One goal of Euromene COST Action is to establish a “sustainable integrated network of researchers in Europe working in the field of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and to promote cooperation between research groups.
Coordination and collaboration appears to be becoming a bigger and bigger theme. The OMF and the SMCI held collaborative and networking meetings last year. The NIH research centers are collaborating on one large project. Canada’s May Montreal conference is focusing on establishing cooperative efforts to understand ME/CFS. (Dr. Scheibenbogen will be attending.) The OMF’s next conference is set for September of this year.
However Dr. Scheibenbogen got interested in ME/CFS, it’s great to see her get so involved so quickly. She reminds me of another relatively new researcher in the field – Dr. Maureen Hanson – who quickly cranked out research studies and is now leading an NIH ME/CFS research center. It’s good to see new researchers have success in this field.
Of course, the going is still tough. In an SMCI interview Dr. Scheibenbogen seemed astonished at the lack of opportunities for research into what she described as a frequent and severe disease.
But still the situation is very disappointing with so little support for patients and research and almost no interest from pharmaceutical companies to perform clinical studies. I am a trained oncologist and hematologist and there the situation is so different with so much research and drug development.
Like everyone else in this field, Dr. Scheibenbogen is a pioneer and pioneers by definition have rough going. Like the pioneers of old she’s forging a path through some hostile territory, not as the pioneers did in the old West but this time German medical circles. Her work is getting results, though, results that her colleagues will surely notice. Here’s to a new presence in the field who’s put, perhaps for the first time, Germany – the most powerful nation in Europe – on the ME/CFS map.
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Carmen Scheibenbogen MD is another sign that the ME/CFS field is slowly but surely hopefully catching on. Scheibenbogen is relatively new to this field, but she’s not new to medical research. A trained oncologist and hematologist as well as a physician and Professor of Immunology in Berlin, her research resume includes over 150 publications dating back 25 years.
It can be difficult for them to even begin to imagine how pervasive the experience of chronic pain actually is or to comprehend the experience. That’s understandable. In a way, those of us living with chronic pain live in a different world, a world dominated by pain and our response to it.
We are conducting a research study because we are trying to learn more about the experience of abnormal responses to physical and/or cognitive exertion, which has been referred to as post-exertional malaise (PEM) in past research, in patients with Myalgic Encephalomyelitis (ME) and/or Chronic Fatigue Syndrome (CFS).
