Occupy CFS

Today I am feeling like the Little Engine That Almost Can. I’ve been drafting a post about the Lipkin XMRV study, and my own views on whether it should be completed. After much work, and several thousand words, I’m out of steam. My goal is to post on the blog twice a week, but it will be just one massive post this week (I hope). So in the next couple days, expect a large post chronicling the story of this study and whether patients should expect the results to help advance CFS research.

I think I can I think I can I think I can . . . . .

Today, the CFIDS Association announces its latest research grants and projects. I know many of us want to dive into the details of the grants, but I want to first take a look at the big picture. The Association describes its research program as an “institute without walls” and all the pieces of the program are designed to work together. With a $2 million investment in 2012 and 2013, this program is one of the most diverse and complex in the field.

Before 2008, the focus of the Association’s research program was funding studies initiated by principal investigators. But after the Association re-focused its strategy to put research first, and with the hiring of Dr. Suzanne Vernon as Scientific Director, the research program became multi-prong. In addition to providing direct funding to researchers, the Association created the SolveCFS BioBank  – the first national bank of CFS biological samples and clinical data that any researcher could apply to use. The 2009 grantees were linked, both via computer network and in person, to increase the sharing of information and ideas. Dr. Vernon has presented at dozens of meetings all around the world, and provided expertise to other researchers and institutions. And last year, the Association recruited a Scientific Advisory Board of experts both inside and outside the field.

Positioned at the hub of the wheel, the Association will direct all aspects of the program announced today: maintaining and expanding the SolveCFS BioBank; funding and administering the five new research grants; investigator meetings; Scientific Advisory Board meetings; work with LogosOmix (see below) to create a biomarker hit list; coordination and management of the research program to drive outcomes and results; and, travel to meetings and to build collaborations with other organizations and institutions.

There are five new grants investigating pain, immune/HPA axis dysfunction, neurocognitive impairment, post-exertional relapse, and drug repurposing. Grants have been and remain a key piece of the program. The Association also announced two new BioBank studies today:

• Dr. Leonard Jason (DePaul University), who has done great work on the case definitions used in CFS, will use clinical information from SolveCFS BioBank participants to examine the multiple case definitions that clutter the landscape. Dr. Jason has previously demonstrated the danger that the CDC’s 2005 empirical definition of CFS may include many patients with primary depression. The SolveCFS BioBank has very detailed data on participants’ symptoms, and comparing that data to the case definitions may reveal the utility of one definition over another.
• Dr. Eric Delwart (Blood Systems Research Institute and University of California, San Francisco) will use metagenomics to search BioBank samples for infectious agents. (Listen to a June 2010 interview with Dr. Delwart on This Week in Virology Episode 86) Metagenomics  is an approach to deep sequencing in which all the DNA in a sample is sequenced, including microbes that cannot be cultured. Bioinformatics is then used to sort out the sequences, identifying known and unknown microorganisms in the sample. This approach is similar to that used by Dr. Ian Lipkin at the Center for Infection and Immunity.

CFS patients know the importance of finding biomarkers for this illness. How many of us have longed for a simple clinical test that would definitively say that we do (or do not) have CFS? In 2009, the Association funded a project to mine the published literature and develop a relational database to identify possible etiologies for CFS.  Now LogosOmix, a startup venture, will partner with the Association to develop a hit list of possible targets for clinical biomarkers. The Association plans to shop that hit list to biotech firms and researchers to facilitate development of the markers for clinical use. Details on LogosOmix are scarce, but Association CEO Kim McCleary told me, “LogosOmix is a very exciting project that is a product of the grant made in 2009-2010 to Dr. Bud Mishra at New York University. This project will give us a ‘big data’ tool to help guide the next generation of CFS studies and may have applications beyond the CFS as well. We are still working through various details and will have more information to share in the coming weeks.” When more details become public, I will write about them here on Occupy CFS.

Taken together, these projects address the top issues in CFS research: case definition, pathogen discovery, clinical biomarkers, and treatment development. The CFIDS Association is outsourcing these components to researchers, but is facilitating and coordinating their work. This approach has already proven itself in the outcomes of the Association’s 2009 grants, which resulted in a 7 to 1 return on the Association’s investment.

One more part of today’s announcement deserves mention. Author Laura Hillenbrand  has made a gift of $250,000 to the CFIDS Association in support of the research program. I have admired Laura Hillenbrand for years, and I am truly inspired by what she has achieved while living with severe CFS. Her generous support of CFS research could have an impact beyond the research itself. CFS advocates have wanted a celebrity spokesperson to help legitimize and publicize this illness. While Laura is not offering herself as that spokesperson (and I completely respect that choice), her support of CFS research may help legitimize CFS research in the eyes of the public.

At last year’s NIH State of the Knowledge Workshop,  Dr. Suzanne Vernon pointed out that a major opportunity in CFS research was to make it “silo transparent.” The traditional way of doing research doesn’t work in CFS. Researchers have stuck to their own specialties, and it has been difficult to attract new researchers to the field. One of the major contributors to the advances in treating childhood cancers was that researchers got together and worked through problems together, creating a level of coordination and cross-pollination that would not have existed otherwise. The Association is poised to facilitate the same kind of progress in CFS. This research portfolio resembles, in many ways, a virtual center of excellence. It does not include a clinical care component, something that patients want and need. But rather than wait years to build a physical institution that can provide clinical care, the Association is deploying resources to move research forward and pursue improved diagnostics and treatments now. Hopefully, the answers found through this effort will be deployed in treating CFS patients in all clinical settings, not just one center.

Today, the CFIDS Association announced five new research grants as part of its “institute without walls” CFS research program.* The Association has funded more CFS research than any other non-profit to date, and expectations are high following on the success of the last round of grants.  As in the past, these grants cover diverse aspects of CFS but have a certain synergy in combination. (For information on other aspects of the research program, see Virtually Reality)

• Body systems covered: immune, HPA axis, central nervous system processing, mechanisms of post-exertional malaise
• Expected outcomes: drug repurposing, biomarker discovery and validation, new treatment directions
• Methods: exercise testing, brain imaging, gene expression, epigenetic changes, brain blood flow measurements, body position, proprietary drug repurposing platform
• Principal investigators new to CFS: Spyros Deftereos (Biovista), Patrick McGowan (University of Toronto, Scarborough)

Peter Rowe  (Johns Hopkins Children’s Center) will use a simple test to establish whether central sensitization of the nervous system plays a role in CFS. Central sensitization of the central nervous system results in an amplified response to a stimulus, causing pain and other symptoms. Dr. Rowe has observed that simple position changes, such as a passive leg raise, can bring on symptoms of CFS in patients. This new study will investigate the observation by applying either a real or sham neuromuscular strain to both CFS patients and controls. If only the CFS patients respond to the real strain with increased symptoms, then central sensitization may be involved in CFS. Dr. Rowe’s clinical practice focuses on children and young adults with CFS, but it is unclear from the published materials whether the study population will also be younger patients. Expected outcome: Passive neuromuscular strain could be a cheap and easy clinical biomarker for CFS. It is also possible that manual physical therapy addressing neuromuscular mobility could be used as a treatment to lessen the effects of central sensitization.

Spyros Deftereos (Biovista) will use the company’s proprietary drug repurposing platform to identify new treatments for CFS. Drug repurposing, called “eHarmony for medicine,”  looks for FDA-approved drugs that might be repurposed in new ways. For example, Rituximab is currently approved for use in non-Hodgkin’s lymphoma and several other diseases, but shows promise for CFS patients.  One huge advantage of this approach is that since the drugs are already approved, the decade-plus required to create a new drug is circumvented. Drug candidates could proceed directly to animal model or early clinical trial research. Biovista will screen all FDA-approved drugs to identify treatments for cognitive impairment and unrefreshing sleep in CFS, as well as other CFS symptoms. Drugs identified will then be examined to see if combination therapy might be more effective than using one drug alone. One thing that is not clear from the published materials is why cognitive impairment and unrefreshing sleep were selected as the focus for the study. Expected outcome: A list of approved drugs that warrant further study for treating cognitive impairment and unrefreshing sleep in CFS.

Dane Cook (University of Wisconsin-Madison) will partner with Dr. Gordon Broderick and Drs. Kathy and Alan Light to link and validate information from earlier studies. Dr. Cook has conducted studies on brain imaging and post-exertional malaise in CFS. Dr. Broderick used his 2009 grant from the CFIDS Association to identify gene expression measures in a post-infectious mononucleosis cohort of CFS patients. Drs. Alan and Kathy Light used their 2009 Association grant to identify post-exercise gene expression changes in CFS, as distinguished from several control groups. All of these researchers presented results of their studies at the 2011 NIH State of the Knowledge Workshop. In this new grant, the investigators will examine functional brain imaging and analysis of blood markers after an exercise challenge. Systems analysis will map the links between reported symptoms, brain function, and gene expression of sensory, adrenergic and immune functions. Cook, Broderick and the Lights will attempt to link their findings in order to better understand post-exertional malaise. A potential weakness here is that it appears only a single exercise challenge will be used rather than the test-retest protocol used by the Pacific Fatigue Lab, but that may or may not impact the results of the study.  Expected outcome: Cross-validation of novel blood and brain biomarkers in CFS which may identify contributing factors to post-exertional malaise.

Marvin Medow (Center for Hypotension, New York Medical College) was funded by the Association in 2009 to investigate the role of orthostatic intolerance in the cognitive dysfunction experienced by CFS patients. His research showed that CFS patients with postural tachycardia syndrome had decreased brain blood flow and greater cognitive impairment than healthy controls during an orthostatic challenge. This new grant will allow him to expand that earlier research, and test three interventions that increase blood flow (inhaled supplemental CO2 and two intravenous drugs). Those treatment interventions may help alleviate the cognitive impairment seen during the orthostatic challenge. Results will likely only be applicable to CFS patients who have POTS. Expected outcome: Identification of potential treatments to improve cognitive impairment that is aggravated by orthostatic intolerance.

Patrick McGowan  (University of Toronto, Scarborough) will use SolveCFS BioBank samples to look for epigenetic changes related to the immune and HPA axis systems in CFS patients. Epigenetics is the study of changes in gene expression that are not the result of changes to the DNA sequence itself. Epigenetic changes, frequently the result of environmental factors such as nutrition or infections, cause genes to “behave” differently by activating or silencing their expression or by modifying the way a gene is transcribed. This study will observe the response of immune cells from CFS patients and healthy controls to a synthetic stress hormone, and then survey the genome looking for epigenetic changes in the immune cells. One potential weakness of the study is that it uses banked samples, rather than fresh samples with changes induced by a stressor like exercise testing. It would be wonderful to correlate an epigenetic survey with the gene expression changes detected in the Lights’ ion channel study. Still, this is one of the first systematic epigenetic studies in CFS. Expected outcome: Identifying epigenetic changes in CFS immune cells could identify biomarkers and treatment targets.

*Clarification – I served on the CFIDS Association Board of Directors from 2006 through 2011, but I did not participate in any stage of the review of grant applications submitted in response to the 2011 RFA.

I have devoted substantial energy in the last several years to following the work of, and preparing testimony to, the CFS Advisory Committee to the Department of Health and Human Services. The committee exists to advise the Department on CFS research and issues affecting the lives of people with CFS.

Speak Up About ME organizes the participation of young people with CFS in the twice annal meetings of the Committee. Speak Up also coordinates meetings on Capitol Hill to bring the stories of these kids to Congressional representatives and their staff, and collects and delivers testimony by kids who are too ill to attend.  I have been both moved and impressed by what these children and their families have said at CFSAC meetings. They speak honestly about how CFS is affecting their lives now and their hopes for the future.

Denise Lopez-Majano, a leader in Speak Up, has asked me to help spread the word about Speak Up plans for the spring 2012 CFSAC meeting. The date for this meeting has not been set, but Denise is asking young people with ME/CFS and their families to consider participating in whatever way they can. For more information, please contact Speak Up at SpeakUpAboutME@gmail.com.

The Senate Health, Education, Labor & Pension Committee hearing on Pain in America (read a summary here  or watch the hearing here) made me realize something: it is not just the CFS community that has to struggle against psychogenic arguments and labeling.

Most people in the CFS world are familiar with the theories and pronouncements of Dr. Simon Wessely  and others who believe that CFS has a mental/emotional cause. I won’t derail this post to go over that well-traveled ground. But I was unpleasantly surprised to hear some of the same language and arguments at the hearing on chronic pain.

The first four witnesses (Dr. Lawrence Tabak, NIH; Dr. Philip Pizzo, Stanford; Dr. William Maixner, UNC; and Christin Veasley, National Vulvodynia Association) were truly excellent, and they made many of the same arguments for increased funding of pain research that we routinely make for increased funding of CFS research. But then Dr. John Sarno of NYU delivered his comments, focused on a pain syndrome he calls Tension Myoneural (or myositis) Syndrome. According to Sarno (who coined the term), TMS is physical pain, particularly back pain, produced by unconscious and suppressed rage or other negative emotional states. Sarno stated in his testimony that the physical pain is real and results from physiological changes induced by those emotional states.

Dr. Pizzo was masterful in his responses to Dr. Sarno’s comments, pointing out that we need to be “very sensitive to the words we use.” He contrasted the way cancer pain is perceived and treated, where providers and family rally around the patient, with how pain syndromes like fibromyalgia are perceived and treated. Both he and Dr. Maixner spoke eloquently about the role of situational factors in chronic pain, including lack of access to care, injury from heavy physical labor, and stress-activated genetic pathways. In response to a question from Senator Bernard Sanders (I)(VT), Dr. Maixner described socioeconomic status as a “surrogate marker” for chronic pain, as the incidence of chronic pain is higher among people of lower socioeconomic status. Dr. Sarno, on the other hand, stated: “Poor people are poor and they’re angry. They’re furious. Fury evokes physical symptomatology as a defense against the rage.” Yes, that is a direct quote, as best as I could transcribe it.

It turns out that the reason Dr. Sarno was invited to testify at the hearing was because Senator Tom Harkin (D-IA), chairman of the committee, invited him. Why? Because, as Senator Harkin shared during the hearing, he used Sarno’s techniques (described in Sarno’s four books) to “cure” himself of disabling back pain. Furthermore, a female relative of Senator Harkin’s “cured” herself of fibromyalgia using the same techniques. Senator Harkin expressed disappointment several times that the Institute of Medicine’s report, Relieving Pain in America,  did not address the psychological origins of pain and the possibilities of treating pain with psychological techniques. To be fair, Harkin stated his strong support for increased funding for pain research, but wants research to “look at everything,” including psychogenic explanations for pain.

Dr. Pizzo thanked Senator Harkin for sharing his story, but cautioned that we cannot lose sight of the patients who have tried and not benefited from currently available treatments. Christin Veasley was impressive throughout the hearing, but I especially loved the way she responded to Senator Harkin on this point. She stated that she has tried all the mind-body techniques to manage her own chronic pain, including yoga, biofeedback, stress reduction and more. But none of those treatments have cured her pain. She acknowledged to Senator Harkin that “Your experience is real, as mine is real.” Ms. Veasley pointed out that we can’t expect to understand or tease apart the multiple contributing factors in pain if we don’t research it, and no answers will be found until there is adequate research.

Perhaps I should be grateful that Dr. Sarno was the only witness peddling a psychogenic cause for chronic pain and, indirectly, peddling his “cure.” Perhaps I should not have been surprised that Dr. Sarno and Senator Harkin so vigorously embraced this simplistic explanation for pain. But truthfully, I was appalled, just as I am every time I hear the claim that there is a psychogenic explanation for my own illness. Emotions certainly play a role in coping with chronic pain and CFS, but that does not make emotions the cause of either condition.

Dr. Sarno claims that once patients understand that their pain is a surrogate for their suppressed rage, the “need” for the pain disappears and they are cured. It’s true that I am angry, Dr. Sarno. I’m angry that doctors like you are so dismissive of my experience. I’m angry that inadequate levels of research funding mean I will have to endure advice like yours, in addition to my physical pain, until the real answers to CFS and chronic pain are understood. And despite the fact I have just recognized and acknowledged my anger, I am still in pain and reliant on the inadequate treatments I described in my written testimony to the committee.

Today, the Senate Committee on Health, Education, Labor & Pensions is holding a hearing on chronic pain. This hearing came about through the work of the Chronic Pain Research Alliance.  I was invited to provide written testimony to the hearing on behalf of The CFIDS Association, and the full text of my testimony follows below.  I am honored that my testimony was submitted in memory of Christy Gaffey, who lost her battle with CFS and interstitial cystitis last Thursday. I hope the Senators HEAR our pleas for action to help all of us suffering with chronic pain because Christy, myself, and millions of others do not have time to waste!

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U.S. Senate Committee on Health, Education, Labor & Pensions

Full Committee Hearing on

Pain in America: Exploring Challenges to Relief

February 14, 2012

TESTIMONY OF JENNIFER SPOTILA

This testimony is submitted on behalf of the CFIDS Association of America, in loving memory of Christy Gaffey of Williamsburg, Iowa. Christy lost her battle with chronic fatigue syndrome (CFS) and interstitial cystitis on February 9, 2012 at the age of 52. She was an advocate for these medical conditions and, in days of better health, participated in lobby days organized by the CFIDS Association. With this testimony at today’s hearing chaired by Sen. Tom Harkin — her senator — we recognize Christy’s life and the voice she once gave to all who have been jailed by chronic pain conditions. We implore, in Christy’s memory and for all those who have been lost too early to these conditions, that today’s hearing mark the beginning of serious action to address and curb the personal, family, community, state and national toll exacted by conditions marked by chronic pain.  

Chronic fatigue syndrome is the name of my illness.  I cannot count the number of people who have said to me, “I had no idea that CFS had pain as a symptom.” But it does.  Think about the last time you had the flu.  Did you lie in bed, shaking and aching all over, too weak to sit up? Yes. That is what my pain is like, but it is like that every day. Pain is always with me.  It follows me around like my shadow.  Just as a shadow changes shape with the light, my pain expands, contracts, and tries to swallow me whole.  There is nowhere I go, nothing I do that is unaffected by pain.

Aching, throbbing, heavy, sharp, tingling, stabbing, crushing – all these words cannot fully describe my pain.  Sometimes I lie in bed, weighed down by it.  Or I might be sitting up and feel pain like a lance through trigger points in my back.  My wrists ache, my toe joints hurt.  One day, it’s my calves that tighten and cramp.  Another day, my neck pinches and headaches loom.  There are times when my whole spine is on fire and nothing I do alleviates the pain. There are times when the gentlest touch is more than I can bear, even my husband’s hand on my arm or my hair brushing against my neck.

I’ve worked with physical therapists.  One said there was no hope when my body did not respond to the prescribed program.  My current physical therapist has made great progress in loosening the trigger points in my back, but there has been no change in my overall pain level or experience.  And the catch-22 is that the exertion of going to physical therapy twice a week and the daily stretching regimen does, in itself, increase my pain.  I tried acupuncture, too.  The needles are supposed to be painless, but I felt ropes of fire shooting out from every needle site.

I’ve consulted with pain management experts.  Over the years I’ve tried aspirin, bextra, celebrex, cymbalta, flexeril, gabapentin, ibuprofen, imitrex, lidocaine injections, lidoderm patches, lyrica, pamelor, percocet, soma, topomax, tylenol, tylenol 3, tramadol, venlafaxine, vicodin, and wellbutrin.  Most of these medications either did not help, or helped but came with intolerable side effects. Pamelor caused dreadful acid reflux.  Topomax caused flashing lights in my peripheral vision.  When my doctor decided to discontinue venlafaxine, it took me more than two months to wean off the dose and even then I endured withdrawal symptoms.   I developed a frightening hypersensitivity reaction to tramadol, forcing me to discontinue the one drug that worked very well for me. Opiates like percocet and vicodin were a dream come true.  The few weeks I was on percocet after the tramadol hypersensitivity were the only pain-free weeks I have had in more than fifteen years.  But no doctor is willing to prescribe them for me long term.  Instead, my pain management doctor believes the goal is to keep my pain manageable, not to make me pain-free.

Pain is intertwined with fatigue like a snarl of barbed wire.  Being in pain makes me more tired.  Activity makes me more tired and increases the pain.  I always have to be careful about my physical position – legs and back fully supported, neck not too bent.  Some days, I cannot get out of bed at all.  Even when I am able to function, pain limits what I can do.  I am fortunate not to have intense, localized pain that might prevent me from reaching for an object or moving in a specific direction.  Instead, the pain hovers in the background, creeping ever higher.  The generalized ache grows stronger and louder until it overwhelms every thought or intention. I might take a few steps out of my cell but Pain, my jailer, will always shove me back in and slam that cell door shut.

On good days, I get through the day with a few hours of activity such as cooking or paying bills.  But by the time dinner is over and the dishes are done, I am on the verge of collapse.  A hot pack and bed by 7pm – I feel like a 90 year-old invalid.  On bad days, I max out on all my pain medications.  If I am very lucky, the medications will keep the pain to a tolerable level.  But there have been many nights when all I could do was whimper.  More than once, I have contemplated going to the emergency room for pain relief on nights like that.  But what would they do for me? How would they view me, a 40-something with normal blood work who insists she needs medication for intractable pain? I have never bothered to find out.

Living with this pain is like juggling while riding a unicycle. One lapse of focus, one dropped ball and everything comes crashing down. The delicate balance of rest, medication, and physical therapy will keep the pain at bay, but inevitably, something destroys that balance and the pain comes roaring back. No one can pedal a unicycle indefinitely. I try my best, but sometimes, living with this pain doesn’t feel much like living at all.

My testimony is also posted on Research 1st.

“I came because by being physically present at Occupy Wall Street, I could increase, however marginally, the likelihood that more people would look in my direction.” – Jason Fitzgerald

If you paid any attention to the news in the last quarter of 2011, you know about the Occupy movement.  Occupy Wall Street.  Occupy Oakland.  Occupy Philly.  The verb “occupy” has been plastered on everything from headlines to posters to funny t-shirts.  The movement continues to evolve, but Occupy has your attention and you know what it is.  Occupy is a brand.

I am part of the 99% but I do not agree with all of the aims and tactics of the Occupy Wall Street movement.  I am not an anarchist.  I do not believe that horizontal decision-making is an effective structure for society.   I do not think that capitalism must be eliminated in order to achieve economic justice.   So why am I appropriating Occupy for this blog when I am not part of the movement itself? And why am I applying the word “occupy” to CFS?

The word “occupy” has many meanings, and in its weakest sense it means “to be situated in.”  I have occupied CFS for more than 17 years, residing within the confinements of space, time, and function imposed upon me by the illness since October 6, 1994.  I am situated within a world created and perpetuated by CFS, and so I occupy this space in the weakest definition of that word.

Occupy also means, “To employ, busy, engage (a person or the mind, attention, etc.)” Obviously, CFS engages my attention because I have to live with it every minute of every day.  But I want CFS to engage your mind, too.  I am starting this blog, and speaking out with my real name, because I am weary of the shadows.  CFS is called an “invisible” illness, and out of sight is out of mind.  Some patients are reluctant, for a multitude of reasons, to admit to having CFS or to sign their names to what they say online.  No more.  Not me.  I will speak honestly about my CFS experience – the politics, the medicine, the research, the suffering, and the lessons.  I am doing this to engage your attention, to occupy your mind.

The primary definition of the word occupy in the Oxford English Dictionary is:  “To take possession of, take for one’s own use, seize,” and that is my mission.  CFS took possession of my body on October 6, 1994.  But now, I am taking CFS for my own use.  I am seizing this illness by the throat and shaking secrets out of its pockets like pennies falling on a sidewalk.  I will share those secrets with you here, and I invite you to Occupy CFS with me by sharing your perspective and experience.

Some will wonder why I would spend energy to write a blog, especially when my energy is so limited.  To paraphrase the opening quote from Jason Fitzgerald, I am here in the hope that I can increase, however marginally, the likelihood that more people will look in the direction of CFS.