2012 was graced by the publication of roughly 102 research and treatment studies on chronic fatigue syndrome in scientific journals. (This figure does not include letters, theory papers, reviews…)
One hundred and two research and treatment studies sounds like a lot. That is, after all, a publication about every thing three day and you might guess that this was a year of major advances in ME/CFS.
It was a year of some advances but not really major ones…and when you look at the studies more closely you’ll see why. If you first separate the large, rigorously designed studies from the small ones done on a shoestring, and the potential difference makers from the interesting but not difference making studies, things start to go south pretty quickly. .
Then when you look at the subject matter you realize that chronic fatigue syndrome research is all over the map, when generally means each major subject might, at best, only get a couple of studies devoted to it…
As you do that the 102 number looks weaker and weaker…Then, if you’re really brave you’ll do a search to see what it takes to make progress in a chronic illness.
A Tale of Two Illnesses
If you do a search, for instance, in the big Pubmed medical citations index for chronic fatigue syndrome you’ll bring up 293 pages of citations of published journal articles dating back to 1981 that in some way relate to this disorder. If you do the same with multiple sclerosis you’ll bring up 2744 pages of citations dating back all the way back to 1929.
Now let’s switch the two. The 293 pages of ME/CFS related citations took us all the way back to 1981. Where does the same amount of research take us back to in MS research world? All the way back to Oct, 2011. That means more journal articles related to MS have been published in the past 16 months than in the past 31 years for chronic fatigue syndrome. ( At 20 citations per page, Pubmed lists almost 6,000 journal papers that are in some way related to MS that have been published in just the last 15 months.)
Other chronic diseases show a similar pattern; rheumatoid arthritis researchers take 17 months to eclipse the entire ME/CFS research effort, arthritis researchers take 12 months, HIV researchers 6 months and diabetes researchers a mere 3 months.
That’s the difference between a well-studied disorder and a poorly studied one. Yes, that’s disappointing, disgusting, frustrating, etc. but also think about promise of it all; ie. of what’s available when a disorder gets ‘in’.
Multiple sclerosis ($122 million/year) is not a particularly highly funded disorder. Autism gets $170 million/year and asthma and arthritis ($221/220 million/year) get almost double MS’s take. Liver disease clocks in at a cool $301 million a year, depression gets $464 million and then there are the real biggies; heart disease ($1.7 billion), diabetes ($3.1 billion), and the big bug, HIV/AIDS , which gets with about $3 billion devoted to it year in and year out.
No wonder Dr. Klimas would rather have HIV ($3.1 billion/yr) than chronic fatigue syndrome ($6 million/yr).
There’s a lot of potential out there if ME/CFS can just make its way into the mainstream..but back to last year. About 102 research studies with the words chronic fatigue syndrome (or equivalent) in their titles were done in 2012. That’s not nothing! Let’s see what researchers were focusing on.
Total Research Studies – 79
- Psychological – 13
- Autonomic Nervous System – 12
- XMRV – 12
- Immune – 11
- Other Pathogens – 7
- Epidemiology – 5
- Gene Expression – 4
- Sleep – 3
- Brain – 2
- Metabolism – 3
- Neuroendocrineimmune/Gut/Mitochondrial/Infrared Spectra/Oxidative Stress/Exercise/Test Effort – 1
Far more physiological oriented than psychological oriented studies were done (@ 6:1). The immune and autonomic nervous systems continue to draw the most focus and, given their many interactions we might expect combined studies in the future. With five studies, four on the ANS and one on metabolism, Dr. Newton in the UK was the major contributor to the ANS studies.
With XMRV in the mix, pathogen studies were high (19) but will obviously drop dramatically this year. Besides XMRV pathogen studies included studies on herpesviruses (3), giardia (3) and q-fever (1). The studies were generally not particularly ‘strong’; ie. some were small, some had problems with study design, some were not particularly ‘deep’, one was from Latvia…. That will change in 2013 at least somewhat as the CDC’s, CAA’s and the CFI’s Lipkin/Hornig pathogen study will all hopefully hit the journals. This year will be a key year for pathogen studies going forward.
Immune studies tend to be more rigorous with the strong Fletcher/Klimas and PHANU team contributing studies on natural killer cells, miRNA’s an other subjects. Often operating out of Thailand, Dr. Maes has fewer collaborators but has been prolific in this field and continues to highlight the NF-kB transcription pathway (see below).
Help From the Side?
With limited research on the ME/CFS side we’re going to have to look for help from other disorders and there is some. Extreme fatigue is gaining interest as a research subject. A review paper proposed inflammation played a major role in the fatigue in ME/CFS. A 2012 Brain, Behavior and Immunity series at UCLA focused on fatigue in cancer, chronic fatigue syndrome and diabetes. The editor of the 12 part series, Bower, also contributed a study suggesting similar immune and HPA axis problems may be found in chronic fatigue syndrome and cancer fatigue. Dr. Newton appears to uncovering autonomic nervous system roots to extreme fatigue in a number of disorders including HIV.
A 2012 study implicated two cytokines of interest, IL-10 and Il-8, in ME/CFS, in increased levels of pain, depression and fatigue in cancer patients. A Miller paper out of Emory finding upregulation of an RNase L gene in fatigued hepatitis C patients receiving immune (IFN-a) therapy may be re-establishing that subject as topic of study. Another Miller paper proposed chronic inflammation alters basal ganglia functioning and dopamine levels causing something called ‘inflammatory malaise’ .
Few ME/CFS patients make into studies on other disorders but, with the low funding present it’s important that they start to do so. The CFIDS Association’s win at the Sanofi Challenge with their multi-disorder, ‘silo-breaking’ patient registry may assist there.
Psychological studies cover a very wide field and last year ranged from studies on personality disorders (not increased in ME/CFS), to ‘identity’, ‘cross-cultural differences’, coping styles, PTSD and ‘traumatic symptoms’, sexual abuse, etc.. Belgium (n=4), the UK (n=3) and the Netherlands (n=3) contributed them most psychological studies.
The difference between what researchers focus on and treatment trials focus on is startling. Psychological/behavioral research is one player among several in the research field but it dominates treatment trials with over 50% of all treatment trials focusing on behavioral protocols. (These can include such things as pacing). ( Even that number is misleading as 3 of the other ‘treatment trials’ were on rats. Take those out and about 60% of all treatment trials done last year were behavioral oriented.)
This might be expected in any disorder with limited research; it’s much easier to come up with behavioral interventions than to come up with physiological ones. This year the Amygdala Retraining Program became the first ‘alternative’ mindfulness/meditation program to undergo a clinical trial. (It had mixed results; high dropout rates but improvements in those who remained.)
Four drugs were tested last year, Ampligen (under review at the FDA), a potential ‘game-changer’ (Rituximab) and two (Clonidine, Vyvanse) that may provide symptomatic relief. All, interestingly, had positive results.
Treatment Studies- 23
- Behavioral – 12
- Herbal treatment CFS-like rodents – 3
- Mitochondrial/Qigong/Diet/Nutritional-Psych/Amphetamine/Rituximab/Clonidine – 1
Review/Theory papers were abundant with several intriguing ones on the effects of inflammation and neuro-immune interactions on fatigue. A biomarker review paper by Dr. Klimas suggested we’re getting closer in that area, and anecdotal reports of progress regarding her team are tantalizing.
Total – 27
- ME/CFS Review – 3
- Exercise – 3
- Behavioral/Psych – 3
- Sleep – 2
- Diagnosis – 2
- Case Studies – 2
- Treatment/Tryptophan/EBV/Immune/Inflammation-Fatigue/Pacing/Pain/Study Elements/ Biomarkers/Central Sensitization/infectious mononucleosis/Neuroimmune/Self Reports
Research continues to be very light compared to other chronic disorders. Pathogens were the top research focus last year but that was largely due to interest in XMRV and otherwise pathogen research was relatively weak. Pathophysiological research dominates the ME/CFS research study agenda with ‘high’ interest in the immune and autonomic nervous systems and psychological research (itself a very broad field) remains a major emphasis. Interest in the role the immune system plays in producing fatigue appears to be increasing and chronic fatigue syndrome is getting significant mention in neuroimmune models of fatigue.
Treatment trails are dominated by behavioral studies but the four drugs tested this year all had positive results.
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