Backdrop
Roughly 100 chronic fatigue syndrome research studies and treatment trials were done in 2012
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.)
Chronic fatigue syndrome research levels lag far behind those of some other chronic illnesses
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
Subject Matter
- 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.
Pathogens
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
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.
Given the low funding and growing interest in the neuroimmune causes of fatigue, collaboration would be very useful
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
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.
TREATMENT
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
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
Conclusion
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.
SUPPORT HEALTH RISING
Very interesting review Cort, especially the research $ comparisons.
I’d be interested to see those same figures compared PER AFFECTED PATIENT (ie, how many dollars spent per AIDS, MS, Liver disease, or arthritis patient vs ME/CFS patient.) Considering the high level of disability of CFS and the significant drop in the AIDS fatality rate over the past 3 decades, you’d think 10% (even 50%!) of the AIDS money could easily be diverted to CFS research with significant benefits to many more people.
It’s interesting too that many cases of MS are now suspected of actually being undiagnosed “Lyme Disease” (aka assorted tick-borne infections). The same may be true of Autism, Rheumatoid Arthritis, and maybe other diseases as well!
Autism and Lyme were both unheard of in the US in the 1960’s. Now they’ve both reached epidemic levels. Coincidence? Too bad we don’t have accurate incidence counts on all these diseases over the last century for comparison!
Despite being the fastest growing vector-borne infection in the country, Lyme Disease and related coinfections suffer from a lack of significant funding just as ME/CFS does.
Hopefully that trend will change in 2013 and beyond. Combining forces may be the key to finding answers to these devastating illnesses.
Julie – I think there are a lot of reasons why HIV/AIDS research is still such a gigantic juggernaut. Although drugs have progressed to the point where most patients can expect it to be a chronic disease rather than a fatal one – the drugs still have drawbacks, some patients can’t tolerate some drugs, drug resistance is always going to be a problem in such a rapidly evolving virus, and they’re now starting to see some of the long-term effects of people being on these drugs for decades.
It’s also worth noting that the situation in Africa and other places is still extremely dire – the drugs are expensive, the prevalent HIV strain there is different, and prevention strategies still face a lot of cultural obstacles. The HIV/AIDS research carried out in the US is not intended to be only for the benefit of US patients.
With all that said, I think there are still arguments to be made for re-allocating at least a sliver of the gigantic budget for HIV/AIDS to other highly damaging diseases that are barely funded at all. In an ideal world, we wouldn’t have to fight over pieces of a limited pie…
Cort, this is a great review article – it’s so hard to get a sense of the big picture from day to day. One note, I think you might have explained, in your paragraphs about funding for ME/CFS and other diseases, that you are giving *only* the figures for NIH funding (at least it looks that way from the numbers given) and not funding for the various areas of research from all sources including private donors. (That would be interesting to know, although I have no idea how the info could be gathered.)
Thank you for the birds-eye view of the research terrain pertinent to ME/Cfs. Very interesting.
Thanks Zac…I like the phrase ‘research terrain’; I think I’ll borrow that from you in the future. 🙂
Yes of course you may.
By the way, can you tell me where to find the funding levels for me/cfs versus MS? Also, the prevalence numbers? I sent out what I thought were the approximate numbers (from your blogs), but I didn’t know the source. Thanks.
You can find NIH funding levels for all conditions and disorders here: http://report.nih.gov/categorical_spending.aspx
This was a fascinating and in-depth look at research in 2012. I can’t imagine how long it took to compile all of it. Well done! I will definitely be sharing this post on my Facebook, Twitter and Google pages.
Thanks Chronic Pain hero…as with most of stuff of this kind it started out small – a brief look at the research – and then got larger as it became more interesting. I was glad to find evidence that the same issues ME/CFS patients face are being examined in other disorders and that at least some of the work done in ME/CFS is being used.
Very interesting, Cort – that’s a good point on the mismatch between the emphasis of the research papers (immune) vs the treatment papers (psychological).
A couple of things have the potential to have a big impact this year – if Ampligen gets approved by the FDA and if we can get a Rituximab trial going. Getting immune therapies seen as valid for ME would have a huge effect on legitimising our disease and pulling in research funds.
Agreed, those would be two huge wins..There are some interesting immune drugs out there that are either in development or aren’t being used much and Dr. Newton is looking at some autonomic nervous system effecting drugs in the lab. (Still haven’t found what those are :))
Thanks, Cort, for the nice compilation of 2012 research data and the handy links so that we may read more.
I did a fast search on the American Diabetes Association website since its allotted research money is coming in at 3.1 billion. I learned that there are 25.8 million diabetics in the US including 7 million undiagnosed and 79 million potential sufferers waiting in the wings. I was astounded at the severity of and number of associated conditions that occur with this disease.
That being said, I have no qualms in stating that our disease is comparable in severity. But why the discrepancy in government spending per sufferer? (We keep asking ourselves.)
The diabetic’s medical costs are 2.5 times higher than those without the disease. It would be interesting to see that statistic with regards to ME/CFS. It may be that we, individuals with ME/CFS, aren’t costing the government/ insurance agencies enough.
On another note, looking at fatigue in other diseases (such as cancer) could turn out to be very helpful for us. I am heartened by that news.
Conclusion: with a budget of 6 mlj it takes another 100 years before they wil find something. Problem with ME/CFS is that we speak about different courses. Greets, John
Thanks very much for the insightful and cogent review, Cort! Really appreciate your hard work and ability to make far-reaching information accessible, even to addled brains. This is so important, and I’m so tired. Thank you, thank you.
That fatigue does get in the way doesn’t it? :). Hope you feel better!
Thanks, Cort. Same to you. Same to all of us!
Very interesting Cort – thanks!
What concerns me is that, even with funding which is orders of magnitude greater than that allocated to ME/CFS, are they getting any closer to effective treatments or cures – or even identifying the core pathology?
Not very encouraging for us I’m afraid.
MS patients do have access to fairly effective treatments (for many cases), don’t they? I have a couple of friends with MS and once they got proper diagnosis and treatment, they got much better and they are functioning well today.
I’m aware this is not the case for all MS patients, but many, I think? So they seem to be getting somewhere with all that money and all those studies…
What little I’ve read about MS treatment seems to indicate that treatments for MS have improved substantially in the last 5-10 years or so, with more medication options becoming available.
I don’t think a “cure” is really the goal we should be looking for – there are so many diseases that don’t have a cure, but which can be controlled to a greater or lesser degree. We really don’t develop a lot of new ‘cures’ these days, but if a disease can be controlled to the point where the person can function more normally and suffer less distress -I’ll take that happily.
Call me a crazy dreamer, but I’d really like us to understand MS, ME/CFS, and similar chronic conditions to such a degree that we could start talking about *prevention* strategies. It would be so much better to save people from getting attacked by these diseases in the first place.
Emma and Anne
I’m sure you are both correct that MS treatments have improved markedly in recent years – I’m not close enough to it to know. Although I stand by the point that progress is slow even when research into illnesses is well funded and funding for ME/CFS would need to increase radically before we can expect similar progress. Without a major (serendipitous) breakthrough we’re currently a long way from effective treatments.
I also agree that a cure is too much to ask for and my personal view is that a ‘cure’ is unlikely as I feel that part of the problem is constitutional. I do remain optimistic though that with proper treatment we might be able to return to something approaching normal levels of function.
Great article, Cort, and I love the ‘countback comparison’ between CFS research and other diseases – it really highlights the funding gulf between CFS and even modestly-funded illnesses. I also think you are right that not a whole load of progress was made last year, like most previous years. Chronic illnesses are very hard to crack anyway (RA and MS are still not well understood) and it just shows the scale of the challenge. Hopefully the Chronic Fatigue Initiative’s work will help kick start bigger and better funding, and maybe even the NIH will pitch in with something meaningful? Here’s hoping.
I was afraid someone was going to bring up what Marco brought up:). That certainly occurred to me to…Some reasons for hope; yes, it often takes alot of research for treatment options to show up in a chronic illness and there is the possibillity of serendipity – something that just happens to show up quickly…
Even 10 or 20 percent increments of improvement can be very helpful; I think I’ve probably given up on the idea of being able to really ever exercise with this illness but I would absolutely love and I think I would be quite satisfied to go on regular long walks with my dogs without getting hammered. That would just be wonderful.
If it works out I think the CAA’s drug repurposing studies could be really important. I talked to Kim McCleary at the FDA meeting; she said the results are going to surprise people and one surprise is going to be that the current drugs used do not appear to be particularly well matched to ME/CFS – at least based on the computer program that was used; ie some drugs that aren’t being used the computer graded out as better fits for this disorder…It was just a quick conversation….that’s all I know…
That study should wrap up in the first half of this year.
Great piece Cort,
Your not just looking back at 2012, but also your ability to think out of the box as you look back.
Thanks for another great read.
Bob
I have known a few people who have had vascular accidents after Air travel when the number of passengers was very high, or the airports jammed or socked in. Then there is Christmas shopping. I don’t think we will find any one virus that becomes virulent enough to cause ME/CFS,though we have two involved retroviruses, or possibly more.
I think we will have a list of pathogens that are capable of serious or critical diseases. If you have lived with some severity of FM/ME/CFS for 50 years, ME began in 1981 San Francisco, it is not hard to remember many flares that abated, energetic summers followed by one cold or flu that did not fully resolve before the next one hit.
I think virulence capable pathogens need to be restrained, by a change or many changes in the conditions that promote virulence. Since the emergence of urbanization and Industrialization, World Wars, we have made every innocent, stupid, or commercial mistake possible and the pathogens are getting very virulent.
Flying through areas with garbage cans and enormous dumps, among other sources birds have begun to carry more and more illnesses, then they nest in rural areas into which we increasingly prefer to live. They live above us, nesting, their sewage being turned into flecks. If a dry season is followed by a dry, dusty wind, we are exposed. Masks are just coming into serious use, but within our children’s lifetimes, they will become mandatory in some seasons and situations.
I don’t know whether it is psychic numbing or simple denial, but the result of this is that we are not training enough people to cope with future needs.
Many popular research diseases are falsely seen as simple in etiology and effect. ME does not lend itself as easily to this as “sugar diabetes”. Obviously caused by sugar, right? Because one major way to fight diabetes is to stop responding to your sweet tooth, sugar is something to avoid, but it isn’t the whole answer.
The genes that cause different manifestations from a pathogen at a standard level of virulence resemble less and less the patient monk Mendel and the color of his sweet peas. Non-Mendelian genetic trends are increasingly common as our bodies respond to major mutagens, and these have not been around long enough for
us to even understand what will happen to babies born into heavily contaminated environments.
My grandfather’s doctor specialized in what was called ME in the 30’s. San Francisco set its database up differently, but my Grandfather got it in the kitchen at the Saint Francis where he was a chef. These were the days when open flame gaslights were common indoors, gas grills heavily exposed chefs. After treating everything that resembled infection, he recommended that my grandparents buy a wood grill in Oakland and they moved to the Diamond District where many immigrants lived. If my grandfather never walked again, my grandmother could find a girl to help.
The conditions were suitable to an epidemic, and it happened. So we have a complex infectious disease which can be made worse by endocrine and neuro-toxins, genetic and CNS damage, and major mutagens.
I don’t think the one cause, one disease, one pill paradigm is likely, not just in ME, but in any natural function or dysfunction. Read Thomas Kuhn’s little book on paradigms and how they shift in scientific and medical communities. The diseases that get the research dollars may be seen through fictive paradigms created to get the big dollars, and sometimes this money was diverted from our funds.
My grandson’s mother lived on the backwater of a Dioxin contaminated river. When she was carrying him on an escalator a nurse got on next too her and said “That baby’s color isn’t right.”
She was soon on a hospital. The last three years have not been pleasant. Why go to school when you aren’t going to get to grow up? Why make friends with kids who will. He’s a little off there. His first best first was taken in for an appendectomy that turned out to be cancerous.
We need to find patience and compassion. ME/CFS patients need fairness, and a fair slice of the research pie. So many mistakes have already been made during our headlong plunge into technology, that we need to think hard about how to engage allies on every level of society. We need quality of life at home and we need more caregivers. Caregivers are good for communities because their money is spent locally.
Thanks Kathleen – your story really makes it clear how many possible causes there probably are for ME/CFS; if you include fibromyalgia and other disorders like it with it in a broad category of fatiguing, sleep impairing, exercise and cognition impairing illnesses then you can find all sorts of triggers from infections to accidents to ‘chronic stress’, to spending time in critical care, to being treated for cancer…to even having an autoimmune disorder. All of these disorders have at least a subset of very ill, ‘fatigued’, exercise intolerant, etc. individuals in them.
Given the InternTional Consensus Criteria have clearly defined myalgic encephalomyelitis (me) is it not time to drop the name ME/CFS – ME is ME. If you don’t have post exertional malaise you don’t have ME. It would be nice to have a line drawn in the sand and all the old names/confusion etc dropped. The name CFS trivialises a very serious disease and does ME patients a huge injustice.