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The Biggest Research Funder in the World on ME/CFS: The NIH on ME/CFS in 2012 Pt. I:

Posted by Cort Johnson

The NIH on ME/CFS Part I

We just did an overview of what a governmental British medical agency is funding on ME/CFS.  Now we turn to the biggest medical research funder in the world – the NIH. While NIH’s contribution to CFS research is paltry ($6 million/year) given their resources ($30 billion plus/yearly), their penchant for funding large, complex and expensive studies means they’re a very important player in ME/CFS research.  Even with their weak focus on ME/CFS they are still the biggest single ME/CFS research funder in the world; in other words what they think and do with ME/CFS matters –  a lot.

The Trans-NIH Working Group (ME/CFS Working Group) – The ME/CFS Working Group, the group responsible for guiding and funding CFS research at the NIH, has just released their first Program Announcement in three years. Program Announcements are important because they give us a snapshot of (a) what the NIH believes ME/CFS is and, more importantly, (b) what NIH states they will fund.

Now is a good time to look at what the NIH thinks ME/CFS is, what they say they are willing to fund, and what changes have occurred over the past four years.

The NIH on ME/CFS in 2012

CFS is Out  – ME/CFS is In –  In contrast to the CDC, which has asserted that myalgic encephalomyelitis and CFS are separate disorders, the NIH  now believes they are essentially the same disorder and states that chronic fatigue syndrome (CFS) is ‘sometimes referred to as myalgic encephalomyelitis (ME)’.  In a distinct change from past PA’s, the term ‘CFS’ is gone and has been replaced  by ‘ME/CFS’ throughout the document.

Not Just Any Type of Disorder….A ‘Regulatory Disorder’ – This Program Announcement (PA) indicates that the NIH believes chronic fatigue syndrome is not a one-hit disorder emanating from damage in one organ but a complex disorder caused by a collection of errors that occur across multiple systems.

These aren’t just any systems either; the NIH believes that ‘the many symptoms present’ in ME/CFS suggest that ‘subtle perturbations’ in the systems of the body responsible for homeostatic regulation are involved…. They believe ME/CFS is a disorder in which something…an infection, stressor or (?) has somehow discombobulated the body’s regulatory systems making it difficult to keep up proper blood pressure, blood flows, neuroendocrineimmune functioning, etc.  It’s also a disorder in which major systems of the body are not ‘talking well to’ (i.e. regulating) each other.

A Chronic Pain Disorder  As Well – ME/CFS is usually called a chronic fatigue disorder but the NIH believes it is also a ‘chronic pain disorder’ which shares important commonalities and perhaps a similar underlying cause with other disorders such as fibromyalgia, TMJ, interstitial cystitis, and irritable bowel syndrome. It’s not clear if this theory is correct; there are similarities and differences between these disorders, but if ME/CFS does fit in this group then it could benefit enormously from discoveries in these other fields.

An Aside: A Broad Pattern of Neglect Continues  – The NIH has held this belief for over ten years but unfortunately, except for the recent creation of an Inter-agency task force, has made so few efforts (joint conferences, joint studies) to support  inter-disease collaboration, that these fields have essentially developed separately. (Ironically, one of the major NIH initiatives of the past ten years – the Roadmap Initiative – was supposed to foster interdisciplinary research. That may have happened with respect to some other disorders, but not in these field)  That may be changing in small degrees but with the NIH being unwilling to significantly support any of these disorders, the inertia is tremendous.

Fibromyalgia, for instance, effects 4 times as many people as ME/CFS, has had several FDA approved drugs for it, is much less controversial than CFS, but has still seen its NIH funding drop 30% in the past 4 years. FM now receives only slightly more funding ($9 million) than ME/CFS ($6 million) and despite all the progress FM researchers have made, FM patients actually receive considerably less funding per person than people with ME/CFS.

This pattern of neglect shows up in all the disorders the NIH believes are linked with ME/CFS.  NIH funding for interstitial cystitis funding has dropped over 50% in the past five years, and although IC, a very painful and sometimes disabling disorder, affects between 3-8 million women, the NIH spends only between $1.50 and $4 per IC patient per year on research.  IBS is believed to cost the US economy about $30 billion/year in losses, but the NIH doesn’t even track its expenditures on it.

Please take note that all these conditions predominantly affect women, are complex neuroendocrine disorders that cause a lot of distress and pose high economic burdens but do not usually cause death.

Small But Important (?) Changes in Diagnosis – With the emergence of the International Consensus Criteria (ICC), there has been more interest than ever in the definition question and the CFS Working Group has made some subtle but perhaps significant changes in the PA on diagnosis. The 2008 and other PAs strictly called for the use of the Fukuda definition, but the 2012 document does no such thing and instead simply states that ‘investigators should provide details of the case definition used’ in their study. That leaves the door open for the use of different definitions (and, implicitly, subgroups).

An Emphasis on ‘Systems Biology’  – One area that appears sure to get more funding is systems biology, since the 2012 PA, for the first time, devotes an entire paragraph to elucidating the rewards a computer driven systems biology approach may bring in identifying patterns and ‘networks’  present in subsets of people with CFS. This is, of course, good news for Gordon Broderick, who helped develop this approach with Suzanne Vernon at the CDC and is continuing onward with it at the CAA and was recently awarded a very large grant. The NIH believes this approach will allow researchers to finally find coherent subsets of patients.

Calling For Better Study Design – several researchers, including Dr. Montoya and Dr. Vernon, have called for more rigorous study designs and the CFS Working Group agrees. The 2008 PA made no mention of study design but the 2012 PA devotes an entire paragraph to the subject, stating that improper study design and underpowered studies have made it difficult to reproduce results. The group called for researchers to do careful stratification of patients and controls, to use specific time points to collect samples, to use longitudinal approaches, whole genome analyses, validated biomarkers and/or animal models.

This was a good move; with its mixed groups of patients, not particularly good definition and variable symptoms, ME/CFS is difficult enough to study – requiring researchers to do more rigorous studies should only help.

The NIH on the Biological Cause of ME/CFS – the Physiologic Causes Section

The NIH’s emphasis on systems interactions and regulation, regulation, regulation comes through loud and clear in the Physiologic Causes section. The first priority area mentioned is studying the role neuroendocrine and neuroimmune factors play. Next comes the study of neuro-cardiovascular regulation, followed by the effects of immune factors on dysregulated multiple feedback control systems, then the need to document the dysregulation in major physiologic control systems.

Interestingly enough, the next NIH priority is on why moderate alcohol consumption causes such fatigue and debilitation in ME/CFS – an intriguing but wholly unstudied subject which suggests this group is well versed in ME/CFS symptoms.

Holes – A wide variety of research can be fitted into these broad topics, but notice that, despite studies suggesting unique problems with exercise physiology and metabolism are present, there is no explicit mention of that subject. Despite the well documented gender imbalance existing in ME/CFS there are no calls for understanding why women are more likely to be affected than men.  This is particularly surprising since the disorders the NIH believes are allied with ME/CFS also tend to be dominated by women and ME/CFS has been ensconced in the Office of Research into Women’s Health for over ten years.  The NIH did fund several XMRV studies but except for one line in which infection is mentioned pathogens are not mentioned at all. Oxidative stress is mentioned but only in connection with ‘nutritional deficiencies’ (??).  The mitochondria aren’t mentioned at all.

An Institute Shows New Interest in ME/CFS While Others Falter

The CFS Working Group is made up of various institutes and, unlike the 2008 PA, the 2012 document spells out what kind of ME/CFS research several of the Institutes that make up the Working Group are interested in. Some of the Institutes are clearly never going to be major players in MECFS research.  The National Institute of Alcohol Abuse and Alcoholism, for instance, is probably not going to be funding much research on the effects of alcoholism and ME/CFS, nor is the National Institute of Aging (NIA) going to fund any research on fatigability in seniors with ME/CFS.

The notice from the National Institute of Diabetes and Digestive Diseases (NIDDK), however, suggests that this Institute, which is not now and to my knowledge has never funded ME/CFS research, is now interested in doing so. This is apparently due to a revolution in thinking that has occurred in the interstitial cystitis and pelvic pain research fields. The NIDDK now views these disorders as central nervous system disorders they believe fit very well with ME/CFS, fibromyalgia and other disorders and they have gone so far as to create a rather expensive multidisciplinary framework for (the MAPPK project) to study them.

Check out how strongly worded the NIDDK’s notice is:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – The NIDDK has a particular interest in supporting projects that examine the potential relationships between ME/CFS and urologic chronic pelvic pain syndromes, such as Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS).  Recent epidemiological data reveal ME/CFS, as well as other disorders that share pain as a common symptom, is often associated with chronic urologic pelvic pain syndromes.  This suggests ME/CFS and urologic pain disorders may have common underlying etiologies and may represent manifestations of systemic disease, rather than organ- or system-specific disease.  Studies addressing the potential associations between ME/CFS and IC/PBS and/or CP/CPPS through basic science approaches (to address underlying disease pathology)….are of relevance to the NIDDK mission.

The National Institute of Infectious and Allergic Disorders (NIAID) – a key Institute for ME/CFS – on the other hand, appears to be floundering a bit.  Even after the Rituximab trial and progress in natural killer cells research  there’s no indication that they have any focus at all in ME/CFS. Instead they simply stated which research they will not support (clinical trials).

To their credit the NIAID did fund several XMRV studies including the Hansen, Mikovits and Lipkin studies, and they are funding a Fletcher study and the Schuster viral study, but Dr. Huber and Dr. Klimas had to go to the National Institute of Arthritis and Muscoskeletal Disorders to get their HERV-K18 (endogenous retrovirus) and gene expression studies funded.


Large Words/ Little Commitment – While exception can be made to some parts of the 2012 PA, it provides a sufficient platform to support a variety of ME/CFS research.  Words, however, as we well know, are cheap, and without a commitment to increasing funding and support for ME/CFS at the NIH, the ME/CFS program will surely stay at the bottom of the barrel in funding.

Of the 229 diseases, conditions and research categories the NIH tracks funding for, ME/CFS is ranked 214th in funding at $6 million a year, with its budget eclipsing only such topics as Climate Change, Global Warming, Homicide interventions and hyperbaric oxygen. The NIH spends twice as much on psoriasis, 3x as much on ‘headaches’, 20x as much on multiple sclerosis and 40x as much on asthma as it does on ME/CFS.

The Budget Cut Myth – There is no denying that the NIH is in tough straits financially, but it’s also true that most disorders actually received small increases in funding for 2012 and ME/CFS did not.

Opportunity Missed? –  Scientific conferences are usually associated with major grant opportunities – in fact they are produced in order to prepare for them, but the Scientific Workshop on ME/CFS last year was the exception.  Instead we were told that the NIH would decide on an RFA at the completion of the Lipkin XMRV study in December. The Lipkin XMRV study is due to be completed in March, but with the Science paper being retracted, and  the NCI, NIAID and the Blood Working Group unanimously declaring XMRV was a contaminant, the federal government appears to have made up its mind on that topic – with no grant opportunity forthcoming.

Several years ago we were told that that there were be no special grant opportunities (RFAs) – that the NIH was cutting back drastically in this area – but they continue to pour out.  Since the beginning of this year, 14 RFAs have been released and over 100 were released over the last year.

The NIH can find money to support the work it wants to support. As of yet it has not decided to support CFS in a meaningful way and it’s unclear how – absent a discovery like XMRV – that’s going to change in the foreseeable future.  That said, the NIH is funding some very important studies –some of which are due to be completed soon.

Check out Part II of the NIH on ME/CFS 2012 for a roundup of  the studies the NIH is now funding. (To be released soon.)


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