Archive for June, 2017

Simmaron Goes to Washington

June 25, 2017

Simmaron, Meet CFSAC

simmaron logoStarting this week, Simmaron Research will serve as one of three non-voting organizations on the federal Chronic Fatigue Syndrome Advisory Committee that makes recommendations to the Assistant Secretary of Health and federal health agencies on the unmet needs of ME/CFS patients.

A federal advisory committee on ME/CFS may not seem like a hot topic but there’s no denying that it’s a vitally important one. Even at its current low levels, the federal government funds many times more ME/CFS research than any other entity. Federal decisions affect how this disease is diagnosed, viewed and treated.  Given that reach into ME/CFS matters, any committee with the potential to effect federal government action is vital indeed.

Since Simmaron Research is committed to redefining how ME/CFS is understood and treated, it will seek to add its voice to others on CFSAC to urge a stronger federal action plan.

An N of One

CFSAC (Chronic Fatigue Syndrome Advisory Committee) is actually special. Many advisory committees exist in HHS and its agencies, but almost all focus on broad biological issues. CFSAC is one of a select few focused entirely on one disease. Formed when the feds were under attack for misappropriation of CFS funds, CFSAC was meant to give ME/CFS insulation from the prevailing bias in federal agencies, and provide a direct avenue to decision makers at the Department of Health and Human Services.

IMG_3223It hasn’t always worked out that way. CFSAC has provided many strong recommendations to the Secretary or Assistant Secretary of Health over the years, some of which have been acted on, but many of which have not, to the deep frustration of the community.  The committee’s potential, though, is great. CFSAC’s twice yearly meetings provide one of the only constant forums for dialog between the ME/CFS community and federal health agencies, and it is a critical window into federal work, as well as a reminder of the extent of patients’ unmet need. It’s strength is its unique blend of government-appointed outside experts, advocates and federal representatives.

CFSAC has had it’s shining moments. Its rejection of Dr. Reeves’s reappointment as CDC ME/CFS chief almost certainly played a role in his ouster when the Obama administration came in. Arguably the most important report in ME/CFS’s history, the Institute of Medicine (IOM) report “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness“, came out of CFSAC recommendations and was initiated by the committee’s Designated Federal Officer. Similarly, the “NIH Pathways to Prevention” report on ME/CFS research needs, which provided the foundation for the upcoming establishment of the first NIH Research Centers for ME/CFS in over 15 years, emanated from CFSAC recommendations and NIH’s ex-officio to the committee.

A New CFSAC Member (Who Isn’t New to CFSAC)

Robert Miller and patients seek NIH funding at CFSAC, 2010

Robert Miller and patients seek NIH funding at CFSAC, 2010

ME/CFS advocate and Simmaron board member, Courtney Miller, will represent Simmaron Research and the ME/CFS patient community at CFSAC for the next two years. Married to longtime patient Bob Miller, Courtney is an experienced advocate who will continue to push the federal government to increase the resources this disease so desperately needs.

The Millers’ advocacy efforts, which date back decades, include many presentations at CFSAC and participation at ME/CFS meetings and conferences, such as the NIH State of the Knowledge Conference, the FDA Advisory Committee on Ampligen, the NIH Pathways to Prevention Working Group, and the Institute of Medicine Workshop.  Over the years, she and Bob Obama and Courtney questionhave met with numerous high-ranking federal officials, including soliciting a promise from President Obama at a Town Hall meeting which led to a high-ranking official from his administration engaging in ME/CFS matters. Working with many advocates, Courtney has helped prepare pages of recommendations to NIH to inform its renewed research program. Their goal has always been stronger research funding and access to treatments for ME/CFS patients.

A Look to the Future

Simmaron Research believes great opportunity for an impactful federal program on ME/CFS is ahead of us.

The compelling IOM and P2P reports and increasingly prominent ME/CFS research publications (including Simmaron collaborations) marked a turning point in 2015 for the federal government and the disease. Director Francis Collins announced a renewal of NIH’s ME/CFS research program and brought it under the leadership of Dr. Walter Koroshetz, Director of the National Institute for Neurological Diseases and Stroke (NINDS).  A comprehensive NIH Intramural Study is underway and new NIH research centers will soon be funded. A reinvigorated community advocacy campaign led by SolveMECFS and MEAction is generating increased Congressional and media scrutiny. The building blocks of a sustained, permanent program to improve federal action on ME/CFS are starting to come together.

Sacramento Millions Missing Rally June 2017

Sacramento Millions Missing Rally June 2017

“Given the advances in science and increased recognition of ME/CFS over the last couple of years, I believe we are facing the best opportunity in this disease’s history for a federal response worthy of patients’ crushing unmet need. And yet, we have a long way to go. I hope to work together with advocates to build on the momentum of CFSAC to achieve increasingly higher levels of interaction and engagement with federal agencies responsible for our health. The government’s primary goal has to be finding evidence-based treatments for seriously ill patients.” Courtney Miller

Simmaron hopes to continue the strong advocacy of the patient organizations that served for the last two years on CFSAC and the experts who continue to serve.

CFSAC:  The Nuts and Bolts

One of ten advisory committees overseen by the Office of the Assistant Secretary of Health (OASH), CFSAC is tasked with providing “advice and recommendations” to the federal government on everything from federal research efforts to disability to provider information.

CFSAC consists of 13 voting members from the research, healthcare and patient communities, 8 non-voting ex-officio members from branches of the federal government (CDC, NIH, FDA, etc.)  and 3 non-voting members from patient organizations.  The three non-voting members from patient organizations now include Simmaron Research, The Massachusetts CFIDS/ME & FM Association and ME Action.

CFSAC holds two two-day meetings a year: a webinar-based meeting and a public meeting.  The meetings usually contain presentations on ME/CFS from invited experts, patients and caregivers; reports from internal CFSAC groups on topics of interest; reports from the NIH, CDC and other branches of the federal government on their activities; and conclude with recommendations to the Assistant Secretary of Health from CFSAC itself.

Courtney Miller will be presenting on Simmaron’s behalf in the next CFSAC meeting in four days on June 29th from 1:30 to 2:30 pm EST. Check out CFSAC’s agenda and listen to her’s and other’s presentation using this call in number (1-888-788-9429) and Passcode: 4510479

The Evolution of a Chronic Fatigue Syndrome (ME/CFS) Researcher? CBT Proponent Calls for More Herpesvirus Research

At times Dr. Wyller of Oslo University has seemed more like a Norwegian version of Simon Wessely than anything else. He’s shown that biological issues were present in ME/CFS, but always manages to come back to the psychological or behavioral elements he believes are perpetuating the disease. His new research, however, is taking him in another direction.

anxiety-fear

Wyller appears to believe that the fatigue in ME/CFS is the result of a false alarm in the same way that pain is in fibromyalgia

Wyller’s research group has highlighted sympathetic nervous activation and inflammation in chronic fatigue syndrome (ME/CFS) adolescents. His “sustained arousal” hypothesis, however, is a mishmash of physiological (infections, genetics) and psychological components (psychosocial challenges, illness perceptions, poor control over symptoms, “inappropriate learning processes”, personality traits, etc.).

That hypothesis posits that a “false-fatigue alarm” state exists in ME/CFS which is largely held in place by classical and/or operant conditioning. That conditioning can be ameliorated by behavioral techniques which tamp down the “alarm” and the sympathetic nervous system activation.

Wyller’s belief that ME/CFS is an infection/stress triggered disease of sympathetic nervous system (SNS) activation, however, took a hit when clonidine – an SNS inhibitor – actually made ME/CFS adolescents worse. Since SNS activation is arguably present and would certainly contribute to the inflammation in ME/CFS, that result probably shocked just about everyone. It suggested, though, that just as in some cases of POTS, the sympathetic nervous system activation found might be a compensatory, not pathological, response to the illness.

Wyller  admits that that CBT’s “effect size” is “modest” and that there is little evidence that it helps sicker patients, but asserts that the evidence-base is “so-solid” that it should be attempted in every patient.

“We believe the evidence base for cognitive behavioural therapy is so solid that all patients with chronic fatigue syndrome/myalgic encephalomyelitis should be offered this treatment.” Wyller et. al.

Wyller 2017: the Evolution of an ME/CFS Researcher?

Wyller may be a CBT/GET apologist, but he’s mostly done physiological research, and whatever his CBT/GET beliefs, it’s difficult to pigeonhole him. His failed Clonidine trial constituted a biological approach to ME/CFS plus his 2016 followup study suggested that a genetic polymorphism in the COMT gene may be responsible for reduced physical activity and impaired sleep and quality of life in some ME/CFS patients.

It’s Wyller’s latest study, however, that takes him into entirely new ground. To his credit, he’s allowing the data to lead him where it will.

Wyller is clearly heavily invested in CBT/GET, while his Norwegian counterparts, Drs. Fluge and Mella, eschew CBT/GET and focus on Rituximab and immune modulation. Wyller mentioned Rituximab in his 2015 overview, but not surprisingly gave it short shrift because of the lack, what else, of follow up studies. But here’s Wyller in 2017 with a study that’s pointing an arrow right at the B-cells in ME/CFS and perhaps even Rituximab.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. Chinh Bkrong Nguyen,1,2 Lene Alsøe,3 Jessica M. Lindvall,4 Dag Sulheim,5 Even Fagermoen,6 Anette Winger,7 Mari Kaarbø,8 Hilde Nilsen,3 and Vegard Bruun Wyller. J Transl Med. 2017; 15: 102. Published online 2017 May 11. doi:  10.1186/s12967-017-1201-0

Using his own definition of ME/CFS, Wyller and his research team took a deep look at gene expression using a technology called high throughput sequencing (HTS) which has not been used before in ME/CFS. You never know what exploratory studies like this will turn up.

The 176 genes whose expression was highlighted in the ME/CFS group most prominently featured a down-regulation of genes involved in B-cell differentiation. The activity of five genes involved in B-cell development, proliferation, migration and survival were significantly reduced in Wyller’s ME/CFS adolescents.

Wyller chronic fatigue syndrome

Wyller’s research is leading him into some unexpected areas

This finding, Wyller reported, jived with findings from the Australians of decreased levels of some B-cells and increased levels of others. (Decreases in the gene expression of genes regulating B-cell proliferation could result in either reductions or increases in different types of B-cells).

At the same time the B-cells in his ME/CFS adolescents were taking a hit, the expression of their innate immune system genes were being upregulated. Interestingly, given the idea that a pathogen is whacking the B-cells in ME/CFS, the expression of several genes associated with pathogen defense were increased in ME/CFS. (Wyller, in fact, reported this was the first time that increased expression of genes associated with innate antiviral responses has been seen in ME/CFS.)

Then, remarkably, Wyller – who recently criticized antivirals as he argued that CBT/GET should be the treatment of choice in ME/CFS – asserted that this finding could reflect problems his ME/CFS adolescents were having with clearing latent herpesviruses.

They “might suggest less efficient viral clearance or reactivation of latent viruses such as members of the herpes virus family, in the CFS group” Study Authors.

Then Wyller suggested that “inefficient viral clearance or reactivation” or chronic viral infection-triggered immune dysfunction warrants further study in ME/CFS.

Then he referred to a remarkable 2014 German study which suggested that a deficient B- and T-cell memory response to EBV may be making it difficult for ME/CFS patients to control EBV infections. That’s really no surprise to the ME/CFS community; it’s long been clear that infectious mononucleosis is a common trigger for people with ME/CFS and FM – but it’s for a CBT proponent to make the connection.

Herpes viruses continue to show up ME/CFS research

Herpes viruses continue to show up ME/CFS research

Finally, Wyller’s study suggested that neither inactivity nor mood disorders had any effect on the biological findings presented. (One of his earlier studies discounted the idea that deconditioning was a relevant factor. )

Wyller’s findings are good news, not just because he’s been so committed to his idea that “classical or operant conditioning” perpetuates ME/CFS, or that he’s been such a robust CBT/GET advocate, but because he has shown the ability to get funding.

His next step is to determine how effectively the B cells in ME/CFS are responding to EBV antigens (VCA, EBNA-1) before and after the introduction of stress hormones. If he finds that B-cells are not doing their job with respect to EBV, then both Wyller and the ME/CFS research field are going to have a take a closer look at the role EBV plays in ME/CFS. What a switch that would be!

Wyller isn’t the only one diving back into the herpesviruses.  Two Solve ME/CFS Initiative studies are examining metabolic issues in B-cells and cells infected with HHV-6. Plus studies into B-cell issues in ME/CFS are continuing.

One wonders what further positive results would do to Wyller’s view of the appropriate treatments for ME/CFS. Given the tendency of herpes viruses to reactivate during stressful situations, stress reduction techniques (CBT, meditation, MSBR) might, in fact, be useful, but more importantly, so might antivirals, and immune  modulating drugs like Rituximab or cyclophosphamide.

It’s possible that at some point that researchers on both sides of the ME/CFS divide will someday meet in the middle.