The oldest chronic fatigue syndrome (ME/CFS) organization is moving forward creatively. Last month the SMCI produced the Discovery Forum which brought researchers from across the U.S. to network and bounce ideas off of each other. A Patient Registry should be unveiled soon and now we have a new slate of Ramsay grant awards. These awards -named after ME pioneer Melvin Ramsay, are designed to provide researchers funding to produce pilot data and score big NIH grants. Last year’s awards focused mainly on the intersection between pathogens, metabolism and the immune system.

This year’s awards underscore the increasingly important role that European researchers are beginning to play in ME/CFS. This time a U.S. team shared grant awards with researchers from Sweden, Spain, the U.K., Germany, Israel and the U.S.

We last saw Dr. Jonas Bergquist speaking at the other collaborative event of the year, the OMF’s Stanford Symposium. Two of the hottest topics in ME/CFS concern problems with energy production and autoimmunity and the Blomberg/Berquist study will tackle both. Blomberg will expand on his research which found antibodies to a most intriguing protein called HSP60 in ME/CFS. HSP 60 plays a critical role in mitochondrial functioning, has been implicated in immune dysregulation and central nervous system problems and plays a central role in autoimmunity to boot (!)

Blomberg’s prior research suggested that anti-HSP60 antibodies could be interfering with HSP60 functioning in mitochondria and elsewhere to cause severe fatigue and even possibly effect natural killer cell functioning in ME/CFS. Another part of the study will examine the metabolomics of ME/CFS patients to further characterize the putative energy problems present.

As an added bonus, the group will collaborate with Prof. Carl-Gerhard Gottfries of the Gottfries Clinic. Dr. Gottfries is a Swedish psychiatrist who cured his ME/CFS over fifty years ago using a staphylococcus aureus vaccine. The vaccine is no longer being produced but Dr. Gottfries has continued on, running surely the only ME/CFS clinic in the world employing biological means which is largely run by psychiatrists.

https://www.healthrising.org/blog/2015/11/21/gottfries-chronic-fatigue-syndrome-story/

The biggest question in chronic fatigue syndrome (ME/CFS) is what happened? What happened to turn a seemingly ordinary infection into a chronic illness? How did a healthy, active person suddenly or gradually become so ill? Researchers have repeatedly suggested that genetics and the environment worked together to produce ME/CFS. Some underlying genetic weakness combined with some environmental event – perhaps an infection – probably sent ME/CFS patients’ immune or other systems into a tailspin.

Epigenetics – the focus of the SMCI’s second Ramsay Grant award – combines both. Epigenetics examines the changes in gene expression that have occurred over time in response to the environment. Lubov Nathanson used gene expression with Nancy Klimas at the Institute for Neuroimmune Medicine to uncover drug possibilities for Gulf War Syndrome (GWS). (That study suggested that immunosuppressant drugs used to treat rheumatoid arthritis and hormone based therapies were the best choices).

Nathanson’s recent ME/CFS work found that environmental factors had at some point tweaked the DNA of a broad range of immune cells (PBMC’s) so as to potentially affect how those cells functioned, how they grew and died, and how they communicated with each.

Now, with the SMCI’s Ramsay Award under its belt, the team will be digging deeper to determine how the expression of specific cells (helper T cells, cytotoxic T cells, B cells, NK cells, dendritic cells and monocytes) has become altered in ME/CFS. Several immune cells have been potentially implicated in ME/CFS. B-cells are of enormous interest given the success Rituximab has had in some patients. Mark Davis’ preliminary work suggested that T-cells have become activated and problems with natural killer cells have been evident for decades. It’ll be fascinating to see which immune cells have become turned off or on in ME/CFS. Putting a spotlight on those cells should aid efforts to develop biomarkers and treatments for this disease.

Read more about the study here

Investigating alterations in the intestinal virome in ME/CFS

The gut is a third area of major interest in chronic fatigue syndrome (ME/CFS). Every gut study, thus far, has shown major alterations in the gut flora of ME/CFS patients but one factor has been missing from all of them – viruses. That’s a little surprising given that infections, including gut infections, appear to have felled many people with this disease.

It turns out that viruses, like bacteria, are rife in our gut flora (human faeces contain at least 109 virus-like particles per gram), and like gut bacteria, can do harm or help. We tend to think of viruses as bad and of course they can be, but a 2014 study found that some viruses play a key role in repairing and maintaining our gut health. A 2016 finding that the viruses hanging out inside our gut bacteria were less common in the guts of Crohn disease patients again suggested that a healthy gut flora is to some extent a viral gut flora. Other viruses may bring about dysbiosis (microbial imbalance).

It’s clear that no assessment of the human gut is complete without an examination of the many viruses present in it. The third SMCI Ramsay grant award to investigators in the U.K. will be the first to do that. Recent technological advances that allow researchers to study the viruses in our guts in detail will be used to discover which gut viruses are present in ME/CFS patients and what role they might play in their gut health.

Read more about the study here.

Immunometabolism of T cells and monocytes in ME/CFS

From Norway to Sweden and now to Germany, the Europeans are making increasingly important contributions to ME/CFS research. Germany indicates what can happen when a research team makes a commitment to this disease. Since 2014, the German Lobel/Scheibenbogen team has published no less than six studies/papers on ME/CFS, making them possibly the most published ME/CFS researchers over the past three years.

It’s not just about quantity, either. The results have been consistently intriguing. This German team’s 2014 study results suggested people with ME/CFS are having trouble controlling Epstein-Barr virus. In 2015 a potential link (COMT gene polymorphism) between stress, reduced immunity and a predisposition to infection was uncovered. In 2016 Lobel et. al. worked with Fluge and Mella to find antibodies to receptors that control blood flow and other processes in about 30% of ME/CFS patients. In 2017 the team uncovered an EBV antigen that could be the basis for the molecular mimicry believed by some to spark an autoimmune process in ME/CFS.

The SMCI’s Ramsay Grant award will allow this productive team to delve into yet another exciting area – energy production in ME/CFS patients T-cells and monocytes. These immune cells have to rev up their engines – a process requiring quite a bit of fuel – to ward off invaders. If ME/CFS immune cells are as energy deficient as their hosts seemingly are, they might not be able to ward off invaders or regulate the immune system properly. The German team will also stress cells and see what effect that has on their metabolism as well.

Read more about the study here

Energy metabolism has been a focus of the SMCI’s research program. By the time this and the last years Ramsay’s award studies are finished, the SMCI will have explored the energy metabolism of T-cells, monocytes, NK cells and examined the role HHV-6 infections may play in reducing energy production in ME/CFS. Plus, the SMCI is funding metabolomics research as well.

Deciphering antibody reactivities against autoantigens & the microbiome in ME/CFS

The fifth Ramsay grant award goes to an Isreali researcher – and marks the first time in quite awhile that I’m aware of that an Israeli researcher has entered the field. Segal is an interesting guy. A computational biologist at the lauded Weizmann Institute of Science, Segal is a highly published researcher with a primary focus on the gut, nutrition and autoimmunity.

Segal is also a leader in the field of personalized nutrition. He covered the implications of a Cell Journal study showing huge differences in the glycemic responses to different foods that exist in humans in a TED talk. Check out “Wired to Eat” for more on a glucometer based approach to diet.

Segal’s going to tackle two ongoing concerns in ME/CFS – autoimmunity and the gut as he looks for antibodies to both autoantigens and gut microflora. Autoantigens are normal molecules in our bodies that sometimes provoke an immune responses against them. If ME/CFS is an autoimmune disease, then some tissue in ME/CFS patients’ bodies is getting attacked by their immune system, and that’s what Dr. Segal is looking for.

Find out more about this study here.

Conclusion

The SMCI’s yearly Ramsay awards are clearly making good on their ability to nimbly respond to research needs in ME/CFS. It was also very good to see innovative research efforts coming from international community – and the SMCI supporting those efforts; we need all hands on deck to defeat this illness.