Putting Research First

IN T H I S I S S U E

Page 1 SOLVECFSPutting Research FirstNewsworthy Highlights of 2011 (so far)

Page 2 & 3 INNOVATECFSAcceleration to TransformationReturning On Your Investment

Page 4 & 5 INNOVATECFSExpanding Research:Looking to the Future10 WaysScientific Advisory BoardDeepens Association’s Expertise

Page 6 & 7 VALIDATECFSJournal Highlights Reflect MultipleHypotheses and Body-Wide DysfunctionsHi-Fi Sci-Di: Dr. Suzanne VernonOrchestrates High-Fidelity Research

Page 8 & 9 VALIDATECFSThe X Factor

Page 10 CONNECTCFSIntroducing Research1stFederal Agency Updates

Page 11 CONNECTCFSNews BriefsBoard, Staff and Contact Info

Page 12 TRANSFORMCFS The Catalyst Fund

Find links to online material in this issue atwww.cfids.org/SolveCFS/smr-fall2011.asp

Validate. Innovate. Eliminate.

SOLVECFSThe Chronicle of the CFIDS Association of America

Summer– Fall 2011Since its founding in 1987, the CFIDS Association of America has supported important research into the biologi-cal basis of CFS through direct grants to investigators, sponsorship of scientific symposia and meetings, fosteringcollaborations and, most recently, establishing the SolveCFS BioBank. As announced in the fall 2009 issue ofSolveCFS, we have narrowed our focus to stimulate research aimed at the early detection, objective diagnosis andeffective treatment of CFS through expanded public, private and commercial investment. We are transformingfrom a patient support and advocacy organization to one laser-focused on stimulating and supporting research.We are putting research first.

In this issue of SolveCFS, you’ll read more about some of the early products of our last round of research grants(see pages 2–3). You’ll also learn more about these activities:

� We have formed a Scientific Advisory Board of top experts from many disciplinesto advise our Board of Directors and staff on strategic research opportunities.

� We issued a new funding opportunity for projects that build on the most promisingscience to advance objective diagnosis and effective treatment for CFS. By September30, we anticipate receiving 27 full proposals from researchers in six countries.

� We are expanding the SolveCFS BioBank and our collaborations with other researchinstitutions to make the BioBank an even more valuable research resource.

We apologize for the long lapse since our last issue of this publication and hope youhave been able to access our monthly enewsletter, CFIDSLink, and daily updates onFacebook and Twitter. We have recapped the most important news in this issue. On May

24, 2011, we expanded our web-based resources with the launch of a new website called Research1st, describedon page 10. We’ve marked articles that appear on Research1st in expanded form with this icon: .

The Association is fully committed to ending the life-altering disability, stigma and isolation of CFS. We are gratefulfor your loyal support and hope we can count on your continued generosity to make this vision a reality. �

Newsworthy Highlights of 2011 (so far)Two papers associating CFS with a family of gammaretroviruses (including XMRV) have generated lots of headlinesand ample controversy over the past two years (see pages 8–9). Other events have also raised general and scientificawareness about CFS this year; here are several:

Jan. 26: The Food and Drug Administrationannounced that new applications for CFS treatmentswill be assigned to a single division. Previously,CFS applications were scattered to six differentreview divisions.

Feb. 4:Author Laura Hillenbrand educated New YorkTimes readers about her 23-year battle with CFS andthe resilience she shares with Louis Zamperini, heroof her latest bestseller, Unbroken.

Feb. 23: Researchers at the University of Medicineand Dentistry of NJ and Pacific Northwest NationalLaboratory reported on spinal fluid markers that distin-guish CFS, non-recovered post-treatment Lyme diseaseand healthy controls. Katie Couric introduced the storythat night on “The CBS Evening News.”

Mar. 5: CFS was the subject of a major feature in theWall Street Journal, “The Puzzle of CFS.” It spot-lighted Dr. David Bell, some of his long-time patientsin Lyndonville, NY, and the lengthy search for betterdiagnostics and treatment.

Mar. 12: The front page of the Wall Street Journalexplored tensions between CFS patients and researchersin “Amid War on Mystery Disease, Patients ClashWith Scientists.”

Apr. 7–8: The National Institutes of Health hosted theME/CFS State of the Knowledge Workshop, its firstin 10 years.

May: For the first time, the Department of Defenseincluded CFS as one of the eligible topics for itsCongressionally Directed Medical Research Program.

May 10–11: The Department of Health and HumanServices CFS Advisory Committee met to makerecommendations to Secretary Kathleen Sebelius.

May 26: Researchers at the University of Utahreported results from an Association-funded studythat shows potential biomarkers for CFS followinga modest exercise challenge.

June 29: The Institute of Medicine released its report,“Relieving Pain in America,” documenting that 116million Americans experience chronic painful condi-tions (including CFS).

July 20: An independent panel of 26 experts from13 countries published new criteria for myalgicencephalomyelitis (M.E.) and recommended thisterm replace CFS.

July 26: Nature Reviews Neuroscience published a six-page Q&A with four CFS researchers about their viewson CFS, its causes and the future of research.

Sept.: Ladies’ Home Journal covered the challenge ofdiagnosing, managing and living with CFS.

Sept. 5: Joanne Silberner took a look at CFS researchon National Public Radio’s “Morning Edition.” �

INNOVATECFS 2

The CFIDS Association was founded in 1987 and our first dollar was invested in research.Over the first 20 years of service to the community, you helped us fund $4.6 million in researchgrants, host three research symposia and support numerous conferences and meetings. Overthose first two decades, our approach to research followed a traditional model and the studieswe funded contributed to a knowledge base of 4,000 small studies.

In 2007, we carefully evaluated the gaps and opportunities. Three important themes emergedfrom this review:

� The literature was essentially a collection of “one and done” studies with few attempts to vali-date early observations or extend findings. These had limited benefit for improving patient care.

� Studies were hampered by the use of multiple case definitions and the lack of standardizedways of collecting data about patients or samples from them.

� Research priorities were driven by “in vogue” hypotheses, with few organized effortsto connect the dots or link findings from one study to another.

We knew there was a better way to approach research, and so did you.

In 2008, we added a full-time scientific director, Suzanne D. Vernon,Ph.D., to our staff and we asked you to help us:

� fund innovative studies;

� leverage existing data;

� strengthen international collaborations;

� recruit new talent to the field; and

� expand communication among scientists to share ideas,knowledge and data.

You came through and helped us accelerate the pace of CFS research.

Now we want to transform it. Over the next four pages, we report on how we have delivered on the promises made in 2008and what we propose to do next with your participation and support. It is an exciting and pivotaltime, with many opportunities to seize. We hope you agree!

Acceleration to Transformation

The most recent research grants funded by theCFIDS Association of America have supportedthese six principal investigators and the projectsthat were evaluated to have the highest scientificand strategic merit among the 24 submitted dur-ing our 2008 cycle. Funding totaling $647,940was awarded to support these research studies,thanks to the generosity of our donors. This reportbuilds on earlier progress updates and we’llcontinue to keep you informed about additionaloutcomes you made possible.

Gordon Broderick, PhD ofUniversity of Alberta

Molecular patterns ofpersistent immune activa-tion in a post-infectiousadolescent cohort

Objective: To use net-work analysis of gene

expression and endocrine measures to identifybiomarkers that describe the events from infec-tious mononucleosis (IM) to post-infection CFS.

Preliminary Outcomes:� Funding: Three new federal awards totalingmore than $3.5 million

� Publications:>> A formal analysis of cytokine networks inchronic fatigue syndrome. Brain, Behaviorand Immunity. 2010 Oct;24(7):1209–17.

>> Cytokine expression as a potential prog-nostic indicator in post-infectious fatigue.Cytokine. 2010; 52(1–2): SS11–7,81.

>> Plasma neuropeptide Y: a biomarker forsymptom severity in CFS. Behavioral andBrain Functions. 2010 Dec 29;5:76.

>> A pilot study of immune network remodel-ing under challenge in Gulf War illness.Brain, Behavior and Immunity. 2011 Feb;25(2): 302–13.

Returning On Your Investment“What has the Association’s support meant to mygroup and our CFS research? So many things thatit’s actually difficult to put into words. First andforemost, the Association has been and continuesto be our essential portal to the patient population.The Association offers a clear rallying pointaround which researchers can congregate andbegin to organize as a community. This is essen-tial if we are to deploy a clear research strategy,one that avoids unnecessary duplication andmaximizes the delivery of tangible results to thepatient population and their families. Throughthe Association and its supporters, we are slowlybecoming one much larger and much better coor-dinated virtual research laboratory, one with cleargoals and where our roles and interactions asscientists, clinicians and educators are beginningto crystallize. This sense of community has beena vital motivator and has kept our group engagedand focused, enabling us to weather the criticismof more traditional academia and the compara-tively barren funding landscape.

“All of this gives CFIDS Association funding avery special meaning. With every dollar beingcontributed by patients and their families, theseprojects represent a sacred trust if there ever wereone. Looking back, the impact that these donationshave had is nothing short of inspiring. They havechanged the research landscape for CFS. Keypreliminary findings were made possible as adirect result of the patients, their families andthe governance of the Association. In turn, thesefindings have given us a solid scientific beachheadfrom which to apply for much larger grants.Indeed, results generated with Association-directedpatient donations have allowed us to leverage$125,000 in seed funding into three multi-yearoperating grants from the Department of Defense(DOD) and the National Institutes of Health (NIH)totaling over $3.5 million. None of this wouldhave been possible without preliminary researchsupported by patient donations administered underthe stewardship of the Association.

“Also important is the role of this funding in train-ing future clinicians in an area of practice sorelylacking in first-line care providers. Through itssupport of summer studentships in our laboratory,the Association has contributed to the researchtraining of five undergraduate medical studentsand two post-doctoral research staff in theendocrine and immune abnormalities associatedwith CFS. The medical students alone went on to publish three papers in well-respected scientificjournals, with two more currently in preparation.Finally, and perhaps most importantly, thesepatient-funded seed projects are promoting impor-tant changes in government research policy, theinclusion of CFS as a research topic in the recentU.S. Department of Defense funding mechanisms(see page 10) being only one example.”

Kathleen Light, PhD ofUniversity of Utah

Novel ion channel-basedbiomarkers in CFS

Objective: Evaluate post-exercise increases in acid-sensing and ion channelreceptors on blood cells.

Preliminary Outcomes:� Funding: Support from a pharmaceuticalcompany to conduct a treatment trial of FDA-approved medications. Supplemental supportfrom organizations supporting MS andfibromyalgia research to include additionalcomparison groups. Several NIH applicationsare under review, one pending an award notice.

� Publications:>> Moderate exercise increases expression forsensory, adrenergic and immune genes inCFS but not in normal subjects. Journalof Pain. 2009.

>> Gene expression alterations at baselinefollowing moderate exercise in patients withCFS and fibromyalgia syndrome. Journal ofInternal Medicine. May 26, 2011.

>> Evidence for a heritable predisposition toCFS. BMC Neurology. May 27, 2011.

>> Additional manuscripts in preparation andunder review.

“Support from the CFIDS Association for ourresearch program on blood-based biomarkers ofCFS/ME was vital in keeping this program alive.The data obtained using this support made it clearthat we can use post-exertional gene expressionfor selected markers to differentiate patients withCFS from those with other disorders involvingdaily fatigue, like multiple sclerosis, as well asfrom healthy individuals. With this evidence inhand, we are also able to obtain a very strongreview for our next grant application with NIH,which we expect to be funded in a few months;

This figure shows the differences between“communication networks” of immune proteins inhealthy controls (left) and CFS patients (right).

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this new NIH R01 grant will assess whether ourpost-exertional biomarkers can differentiate CFSfrom clinical depression. Objective biomarkersfor CFS will be valuable in diagnosis and tohelp individualize treatments for specific patients.Thank you to the CFIDS Association and itsgenerous donors for this very important support.”

Marvin Medow, MD ofNew York Medical College

Splanchnic vasoconstric-tion is impaired bymicrobiomic nitric oxideproduction reducing cere-bral blood flow in CFS

Objective: To determineif upright posture causes

neurocognitive deficits as a result of impairedcerebral blood flow and modulation of nitricoxide and reactive oxygen species.

Preliminary Outcomes:� Funding: Application to NIH pending review.

� Publications (selected):

>> Decreased upright cerebral blood flow andcerebral autoregulation in normocapnicpostural tachycardia syndrome. AJP Heartand Circulatory Physiology, 2009.

>> Respiration drives phase synchronizationbetween blood pressure and RR intervalfollowing loss of cardiovagal baroreflexduring vasovagal syncope. AJP Heart andCirculatory Physiology. Nov. 12, 2010.

>> Reactive oxygen species from NADPHand xanthine oxidase modulate thecutaneous local heating response in healthyhumans. Journal of Applied Physiology.March 24, 2011.

>> Cutaneous constitutive nitric oxide syn-thase activation in POTS with splanchnichyperemia. AJP Heart and CirculatoryPhysiology. June 3, 2011.

>> Increasing orthostatic stress impairs neu-rocognitive functioning in chronic fatigueand POTS and is not related to cerebralblood flow velocity. In preparation.

>> Additional data being analyzed; manu-scripts in preparation.

“In addition to the obvious benefits of receivingfinancial support from the CFIDS Association thathelps to defray the cost of conducting research onCFS, my research has allowed me to interact withmany CFS subjects during these studies, whichhas put a ‘personal face’ on this syndrome. Thishas increased my appreciation for the need toprovide answers to the many unanswered ques-tions about the cause of and the mechanisms thatunderlie symptoms of CFS. I have also enjoyedproviding information about CFS through our

scientific publications, and the webinars andscientific meetings arranged by the Association.Lastly, the interactions that I have had with otherhealth care professionals I have met through theAssociation have provided useful insights intoCFS beyond the scope of my own investigations.”

Bud Mishra, PhD ofNew York UniversitySchool of Medicine

Translate science toa cure for CFIDS

Objective: To builda knowledgebase forCFS that combinespublished literaturewith experimental data.

Preliminary Outcomes:

� Creation of a digital library of 250,000 full-text articles on CFS, 14 commonly co-occurringconditions of CFS and relevant biomedicalliterature to help decipher CFS pathophysiology.

� Publications:

>> Metamorphosis: the coming transformationof translational systems biology, Queue,7(9):40–52, ACM, 2009.

>> Reverse engineering dynamic temporalmodels of biological processes and theirrelationships, Proceedings of the NationalAcademy of Science, 107(28):12511–6, 2010.

“The main focus of this research program was todevelop novel ‘systems biological’ tools focusingon understanding the causes of CFS. The NYUtools can be categorized into two groups: toolsthat generate novel hypotheses using data on howvarious genomics and related information varyover time and how they differ from patient andpatient (the subject of a student’s PhD thesis);and tools that filter known hypotheses about theprogression of the disease by data-mining the pub-lished literature. By using principled and rigorousapproaches, such tools identify causal bases ofCFS that go beyond anecdotal explanations of thesyndrome. Since the results can be visualized ona computer, researchers thus have the ability tofurther examine the most significant hypothesescarefully and design new studies. In this way, theNYU team’s research has enabled the CFS com-munity to move into the state-of-the-art genomicsand systems biology arena, which would not havebeen possible without the Association’s funding.”

Sanjay Shukla, PhD ofMarshfield ClinicResearch Foundation

Metagenomics approachto study CFS patients

Objective: Determine ifthere is an altered ratio ofgut commensal and patho-genic bacteria in CFS and

if exercise increases microbe translocation tocause post-exertion symptoms.

Preliminary Outcomes:� Secured supplementary funding of from Univ.of Wisconsin-Madison to expand sample size.

� Study data is currently being analyzed andprepared for publication.

“I am really excited to explore the potential roleof the gut microbiome in explaining some aspectsof CFS and I thank the CFIDS Association forfunding this exciting project. Several recentresearch studies have suggested a role for thegut microbiome in modulating chronic diseasesfrom diabetes to obesity to ulcerative colitis.With awareness of those findings, I am reallyexcited to explore the potential role of the gutmicrobiome, especially gut permeability, inexplaining at least some aspects of CFS.”

Dikoma Shungu, PhD ofWeill Medical Collegeof Cornell University

MR neuroimaging assess-ment of cerebral metabolicsubstrates and regionalblood flow in CFS

Objective: Use magneticresonance spectroscopy

(MRS, an advanced MRI method) to measurespecific brain chemicals. The investigators buildupon preliminary evidence showing elevatedlactate in CFS patients. Examine chemicals inblood and brain that are indicators of oxidativestress and mitochondrial dysfunction.

Preliminary Outcomes:

� Funding: NIH award in collaboration withBenjamin Natelson, M.D., with total fundingof $379,000. Another NIH application hasbeen submitted.

� Publications:

>> Ventricular cerebrospinal fluid lactate isincreased in chronic fatigue syndromecompared with generalized anxiety disorder:an in vivo 3.0 T (1)H MRS imaging study.NMR in Biomedicine. April 2009.

>> Increased ventricular lactate in chronicfatigue syndrome measured by H MRSimaging at 3.0 T. II: comparison with majordepressive disorder. NMR in Biomedicine.July 2010.

“As is amply clear, the continuing skepticism thatCFS is not a ‘real’ disease will not abate until thereis foolproof scientific evidence that this debilitatingillness is a distinct medical entity with biologicalor organic causes. To achieve this objective willrequire funding of high-quality, groundbreakingresearch, which is scarce and dwindling. Thelargest source of medical research funding is theNational Institutes of Health (NIH). However,because research funds are limited, it is nearlyimpossible to compete for NIH funding withouthaving strong preliminary data that support thevalidity of new research ideas or hypothesesabout a disease that one wishes to investigate.This even harder for CFS, which has no knowncauses. That is where small research funds thatare provided by dedicated organizations like theCFIDS Association of America assume criticalimportance. With the support of the Association,my collaborators and I have been able to conductsmall but high-quality and critically importantpilot studies that have enabled us to test the valid-ity of some of our ideas about the causes of CFS,and then to use the generated preliminary data tocompete effectively for larger NIH grants to pursuethose ideas. Case in point: using preliminary dataobtained in a small pilot study supported by theAssociation, we submitted a grant application tothe NIH to test ideas that could show that CFS wasnot a psychiatric disease, and were very recentlyinformed that this application has been funded bythe National Institute of Neurological Disordersand Stroke and the NIH Office of the Director,with total support of $379,000 for the collaborativeeffort led jointly by Dr. Benjamin Natelson at BethIsrael Medical Center and Dr. Nora Weiduschatin my laboratory at Weill Cornell. In addition,we just submitted another NIH grant application,based on data generated with funding from theAssociation, to test a drug that we postulate couldalleviate some of the disability associated withCFS. In short, without the type of funding thatcaring organizations such as the Association canprovide, high-quality research into the biologicalcauses of CFS by dedicated researchers would bevirtually impossible due to lack of federal support.We and all those affected by this illness owe thecontributors to the Association’s research fundsa debt of gratitude.” �

This figure from the Journal of Internal Medicinecompares gene expression increases followingmoderate exercise in patients with CFS and FM.

To inform our transition beyond the traditionalrole, we have learned from other organizationsthat leverage their investment in research to getmore from academia, government and industry.We have benefited tremendously from innova-tive research programs developed by the MyelinRepair Foundation (working on myelin repairtherapies for M.S.), the Michael J. FoxFoundation (working for better therapies anda cure for Parkinson’s disease), the Susan B.Love Army of Women (giving all women theopportunity to partner with researchers and takebreast cancer beyond a cure), FasterCures (an“action tank” that works to improve the medicalresearch system) and others.

Now, we look to the future and the opportunityto build on our dynamic program in four majorareas by:

� Funding six to eight new grants from our2011 Request for Applications;

� building a larger, more valuable SolveCFSBioBank;

� developing a biomarker “hit list” to drivefuture research priorities; and

� expanding collaborations and networksof investigators working in the field.

Learn more about each of these initiatives.

New Grants:In April, we widely circulated a new Requestfor Applications that generated 36 letters ofintent. Twenty-seven of the projects describedwere responsive to our emphasis on advancing

objective diagnosis and effective treatment. Fullproposals were invited from those investigatorsand are due on Sept. 30, 2011. All applicants (andtheir institutions) have agreed to revised policiesthat strengthen the Association’s data-sharing andintellectual property policies. Proposals will bereviewed on two levels: 10 measures of scientificmerit by peers in related disciplines, and ninemeasures of strategic merit judged by reviewersfamiliar with the CFS literature and the field.The number of new projects awarded fundingwill depend on the rigor of applications submittedand the amount of funds available through theCatalyst Fund (see page 12).

More Valuable BioBank:In March 2010, we announced the launch of theSolveCFS BioBank, the first combined patientregistry and biorepository of its kind. In its first18 months of operation, the BioBank has enrolled449 participants (including well-characterizedCFS patients and healthy controls) and we havecompleted our first collaborative study. Resultsfrom that study are being analyzed and preparedfor publication. We are now ready to expand theBioBank and can engage participants anywhere inthe world, matching subjects and samples to theneeds of individual investigators. BioBank partici-pants contribute to multiple studies and form thebasis of study by various investigators focusingon different aspects of CFS, creating a “virtualcenter” in which we are partners in the designand conduct of research studies. Through theBioBank, we can deepen understanding of resultsobtained for individuals, subgroups and the popu-lation as a whole. It also helps provide continuityas individual investigators enter and exit the field.

INNOVATECFS 4

4. We developed a rigorous review processto select the strongest research proposalsbased on scientific and strategic merit.

5. We networked our funded investigatorsand required them to work together.

6. We worked closely with our granteesto ensure their projects yielded results.(More on pages 2–3.)

7. We established a patient registry andbiobank for clinical data and samples —the SolveCFS BioBank.

The changes we’ve made over the past three years have transformed our organization andour approach to CFS research. The traditional model, marked by passive support of researchgrants, is appropriate for disease states for which there exist large government- and indus-try-supported research portfolios that can be augmented through private philanthropy. Asyou know, this is not the case for CFS.

Expanding Research:

Looking to the Future

Biomarker Hit List:One of the products of the projects funded in2009–2010 is the knowledgebase generated from250,000 articles about CFS and related areas ofscience (see page 3). Dr. Bud Mishra’s team atNew York University built this knowledgebaseand the text mining tools that will enable us touse these assets to build a data-driven target listof biomarkers. We will then “shop” this list withacademic centers and biotech companies to stim-ulate validation of these target biomarkers usingsamples from the BioBank or other clinical pop-ulations, accelerating the pace of moving fromtheoretical to practical applications for diagnos-tics and treatments.

Expanding Collaborations:In 2009 we networked our funded investigators,bringing them together to discuss their studydesigns, data collection and subject recruitment —before their studies got started. The network wasexpanded to include NIH-funded investigators andhas yielded new collaborations and greater sharingof resources, data and ideas. We are now workingwith NIH and several academic groups to establisha secure data-sharing platform and to standardizeways of defining cases and collecting and analyz-ing data to improve comparability of researchacross all settings and to provide a more formalinfrastructure for collaboration and networking.

These new initiatives will truly transform the waythat CFS research is conducted — not just forstudies conducted with Association support, butfor the field as a whole. This approach reflectsan integrated strategy to overcome the barriersof the past and accelerate the pace of discoveryand implementation for the future. �

Participants fromanywhere in the world

Enhancedresearch continuity

Subjects and samplesto match study needs

Partners in research and design Virtual research center

SOLVECFSBIOBANK

BioMarker Hit List

250,000 Articles About CFSand Related Areas

8. We conducted our first collaborativeBioBank study and enrolled 449 activeparticipants.

9. We engaged researchers, policy makersand patients around the world. (More onpages 6–7.)

10. We have become the leading resourcefor credible research information. (Moreon pages 10–11.)

1. We narrowed our focus to execute the follow-ing strategy: “To stimulate research aimed atthe early detection, objective diagnosis andeffective treatment of CFS through expandedpublic, private and commercial investment.”

2. We deepened our expertise with the addi-tion of a Scientific Advisory Board. (Moreon page 5.)

3. We have learned from and collaboratedwith other innovative organizations workingto end suffering caused by common andrare diseases.

10 Ways the Association Has Readied to Transform Research

Roger Dodd, Ph.D.Vice President, Research and Development and Director,American Red Cross, Holland Laboratory Dr. Dodd’s primary research interest is the epidemiologyof transfusion-transmitted infections, with particularreference to emerging infections. He is responsible forthe Red Cross research programs supporting its bloodprogram and has more than 175 publications on transfu-

sion-transmitted infections. He has been an advisor to the World HealthOrganization, serves on the editorial boards of Transfusion, TransfusionMedicine and Transfusion Medicine Reviews, and is a past president ofthe American Association of Blood Banks (AABB).

Nancy Klimas, M.D. Professor, University of Miami, Miller School of MedicineDr. Klimas directs the Allergy and Immunology Clinicat the University of Miami and is director of researchfor the Clinical AIDS/HIV Research at the MiamiVeterans Affairs Medical Center. A leader in the fieldof CFS research, Dr. Klimas is the past president ofthe International Association for CFS/ME. Dr. Klimas

was the principal investigator of the National Institute of Health’s Centerfor Multidisciplinary Studies of CFS Pathophysiology at the Universityof Miami.

Kelly Morren, B.S.Vice President, Jones Lang LaSalle Ms. Morren is vice president of Jones Lang LaSalle’sStrategic Consulting organization. She is an engagementleader for the Workplace Solutions practice, withresponsibility for client relationships, workplace strategydevelopment, change management and product/servicedevelopment. Her work focuses on the strategy, planning

and management of complex transitions balancing strategic, financial andtactical perspectives.

Dimitris A. Papanicolaou, M.D. Merck Research LaboratoriesBefore joining Merck’s research and development program,Dr. Papanicolaou was a staff researcher of endocrinology atthe NIH and Emory University. Dr. Papanicolaou’s researchinterests focus on cytokines, particularly interleukin-6,in healthy and disease states. His interest in CFS researchbegan with his work at Emory University; he has also stud-

ied sarcopenia, chronic insomnia and the effect of COX-2 selective inhibitorsin acute and chronic pain conditions.

Vincent R. Racaniello, Ph.D.Higgins Professor, Department of Microbiology andImmunology, Columbia University’s College of Physiciansand Surgeons Dr. Racaniello has studied viruses including poliovirus,echovirus, enterovirus 70, rhinovirus and hepatitis Cvirus. He has served on the editorial boards of scientificjournals, including the Journal of Virology, and is a

community editor for the open access journal PLoS Pathogens. He is oneof four authors of the textbook, Principles of Animal Virology. He hostsseveral popular science podcasts including “This Week in Virology” andwrites Virology Blog.

Robert H. Silverman, Ph.D.Staff and Professor, Mal and Lea Bank Chair, Department ofCancer Biology, Lerner Research Institute, Cleveland ClinicDr. Silverman is dedicated to investigating antiviral innateimmunity in health and disease. His studies are focusedon RNase L, a key protein in the interferon responseagainst many viral pathogens. Dr. Silverman also studiesthe role of viruses and human genetics in prostate cancer.

Together with collaborators Joseph DeRisi and Don Ganem (UCSF) andEric Klein (Cleveland Clinic), he discovered xenotropic murine leukemiavirus-related virus (XMRV) during studies on prostate cancer. He is afellow of the American Association of Microbiology. �

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Scientific Advisory Board Deepens Association’s ExpertiseThe CFIDS Association has formed a Scientific Advisory Board to guide and shape its research program. We are honored to have the service of these esteemedexperts representing diverse scientific and strategic disciplines. The formation of the Scientific Advisory Board is another important step in our transition to aresearch-focused mission and our commitment to “Put Research First” (see page 1).

Here are brief introductions to our scientific advisors. Learn more about them at Research1st.

Lucinda Bateman, M.D.Founder, Fatigue Consultation Clinic, Salt Lake CityDr. Bateman’s goal in establishing her clinic and theOrganization for Fatigue and FM Education and Researchis to encourage a more thoughtful evaluation process,sharing of information with patients and medical providersand cooperative research efforts aimed at understanding thecause(s) of CFS/ME and FM. Her focus on these conditions

is inspired by her sister, Shauna Bateman Horne, who had CFS for 15 yearsbefore she was diagnosed with non-Hodgkin’s lymphoma and died a yearlater from complications of a stem-cell transplant.

Italo Biaggioni, M.D.Professor of Medicine, Professor of Pharmacology,Vanderbilt UniversityDr. Biagionni leads a national referral center for theevaluation of patients with disorders of the autonomicnervous system (ANS). He sees patients with variousforms of orthostatic hypotension, orthostatic intolerance,syncope and autonomic forms of hypertension. His

clinical research focuses on the interaction between neural (autonomic)and metabolic (adenosine, nitric oxide) mechanisms that regulate bloodpressure. The program’s goal is to define the role of the ANS in bloodpressure disorders to develop targeted therapies.

Gordon Broderick, Ph.D.Associate Professor, Pulmonary Medicine,Department of Medicine, Faculty of Medicine and Dentistry,University of AlbertaAn engineer by training, Dr. Broderick’s current researchefforts are focused on understanding immune dysfunctionand autoimmunity from an integrated systems perspective.In particular his group is investigating how subtle imbal-

ances between the immune system’s multiple components, as well as itsinteractions with the endocrine and nervous systems, may lead to complexdisorders such as CFS and Gulf War Illness. His group is developing ana-lytical approaches to map the communication network linking the nervous,endocrine and immune systems and to decipher its operation. (See page 2.)

Russell L. Bromley, B.A. Principal, TRAC ConsultingMr. Bromley formed TRAC Consulting to assist non-profit medical research organizations in TranslationalResearch Acceleration via Collaboration. He specializesin designing and implementing strategic research plansand collaborative operational models that are alignedwith an organization’s mission and the unmet medical

needs of patients. Prior to founding TRAC Consulting, he served as thechief operating officer of the Myelin Repair Foundation where he wasinstrumental in the creation, implementation and evolution of the MRFAccelerated Research Collaboration™ model.

Lin Chang, M.D. Professor of Medicine, UCLA Department of Medicine —Division of Digestive Diseases, David Geffen School ofMedicine, UCLA; Co-Director, UCLA Center for NeurovisceralSciences and Women’s Health Dr. Chang’s main area of research is the pathophysiologyof irritable bowel syndrome (IBS) with particular interestsin the overlap of IBS with FM, as well as gender differ-

ences and neuroendocrine alterations. She is an NIH-funded investigatorstudying the central and peripheral mechanisms underlying IBS and shehas conducted clinical trials for functional bowel disorders.

Paul R. DeStefano, J.D. Partner, McDermott Will & Emery LLPMr. DeStefano is a member of the MWE’s HealthIndustry group and the firm’s Life Sciences & MedicalDevices group. He specializes in strategic planningrelated to the formation, finance and operations ofstart-up companies in the biotech industry. Mr. DeStefanois a former chief legal officer of Genentech, Inc., and has

served as an advisor to the Robert Wood Johnson Foundation and NationalAcademy of Sciences on the commercialization of human gene therapy. Hewas also an advisor to the Institute of Medicine on vaccine liability issues.

VALIDATECFS6

BiomarkersSpinal Fluid Proteins: Researchers at sixinstitutions led by the University of Medicineand Dentistry of New Jersey and PacificNorthwest National Laboratory reported finding738 unique protein markers in spinal fluidsamples collected from 43 CFS patients andcompared to samples from 25 neurologic post-treatment Lyme disease patients and 11 healthycontrol subjects. They were able to distinguishCFS from Lyme disease. Proteins identifiedin CFS patients only have been linked toParkinson’s disease and Alzheimer’s. Thisstudy garnered attention from “The CBSEvening News” and other news agencies.(PLoS One, Feb. 23, 2011)

Exercise Challenge Reveals PotentialBiomarkers: Forty-eight CFS patients werestudied and two distinct subgroups wereidentified on the basis of changes to the ɑ-2Areceptor, a key regulator of neurotransmitters inthe central nervous system. The larger group ofCFS subjects (71 percent) could be identifiedwith a combination of four biomarkers (P2XR,ɑ-2A, β-2 and IL10) at any time point within48 hours following the exercise challenge withhigh specificity and sensitivity. The smallergroup showed a large decrease in ɑ-2A, oppo-site of the larger group. This study was fundedby the CFIDS Association; see page 2 for moreinformation about it. (Journal of InternalMedicine, May 26, 2011)

Infectious Agents(see also XMRV-related research, pages 8–9)

Novel Pathogens: Researchers in the U.S. andSweden reported that they examined 45 pairs oftwins discordant for CFS or idiopathic chronicfatigue (one twin had CFS or ICF and the otherdid not) for evidence of novel pathogens. A weakassociation with hepatitis G virus was found innine percent of the cases and zero percent of thecontrols. (BMC Microbiology, Jan. 2, 2011)

Post-SARS CFS-LikeSyndrome: Moldofskyand Patcai studied 21health care workers whohad documented SevereAcute RespiratorySyndrome (SARS) and

were not well enough to return to work oneyear to three years later and compared them toseven healthy females and 21 females who met

Journal Highlights Reflect Multiple Hypothesesand Body-Wide Dysfunctions

fibromyalgia (FM) criteria. They found that thechronic post-SARS syndrome shares clinicaland sleep features with CFS and FM. (BMCNeurology, Mar. 24, 2011)

Brain & Autonomic Nervous SystemAutonomic Function: Forty-four CFS patientsand 52 healthy adolescents were recruited froma pediatric outpatient clinic in Norway. Duringnight-time sleep, heart rate and mean bloodpressure were significantly higher in CFSpatients as compared with controls. Duringdaytime, heart rate was significantly higheramong CFS patients, whereas blood pressureswere equal between the two groups. The find-ings supported other evidence of sympatheticpredominance of cardiovascular control inadolescent CFS patients and suggested apossible target for therapeutic intervention.(Acta pediatrica, Feb. 2011)

Cerebral Blood Flow: Using an MRI techniquecalled arterial spin labeling, this New Jerseygroup compared blood flow in the brains of 11subjects with CFS and 10 age-matched healthycontrols. The CFS patients as a group hadsignificantly lower global cerebral blood flow(CBF) compared to controls. The reductionin CBF occurred across nearly every regionassessed. Nine of the 11 patients showed thesereductions compared to the average control data,while two patients showed actual increases rela-tive to the controls. (Journal of the NeurologicalSciences, Feb. 15, 2011)

Migraine Overlap: Headaches of a new type orseverity is one of eight case-defining CFS symp-toms. Two cohorts of Georgetown UniversityCFS patients were evaluated using standard

criteria for headachesubtypes. 60 percentof CFS subjects hadmigraine without aura;24 percent had migrainewith aura; 12 percent hadtension headaches only;only four percent had no

headaches. Co-occurring tension and migraineheadaches were found in 67 percent of CFSsubjects. Sumatriptan (Imitrex) was beneficialfor 13 out of 14 newly diagnosed CFS migrainesubjects. (BMC Neurology, Mar. 5, 2011)

Impaired Cognition: A group in Belgiumevaluated 25 subjects with CFS, 25 subjectswith major depressive disorder (MDD) and25 healthy subjects using standardized testsof attention, working memory and verbal andvisual episodic memory. Patients with CFS hadslower phasic alertness; they also had impairedworking, visual and verbal episodic memorycompared to controls. This study confirmed thepresence of an objective impairment in attentionand memory in patients with CFS. (ClinicalNeurology and Neurosurgery, May 2011)

Brainstem Dysfunction and AlteredHomeostasis: Researchers in Australia usedstatistical parametric mapping of brain MRimages and compared against clinical scoresfor 25 CFS subjects and 25 normal controls.Midbrain white matter volume was observedto decrease with increasing fatigue duration.

These results are consistent with an insult to themidbrain at fatigue onset that affects multiplefeedback control loops to suppress cerebralmotor and cognitive activity and disrupt localCNS homeostasis, including resetting of someelements of the autonomic nervous system.(NMR in BioMedicine, May 11, 2011)

EEG Spectral Data Distinguishes CFS: Agroup at Harvard analyzed spectral data fromelectroencephalograms (EEGs) performed on70 CFS patients, 390 healthy controls, 24 sub-jects with major depression and 148 patientswith prolonged generalized fatigue, a total of632 subjects. Ten factors distinguished CFSfrom healthy and depressed controls, with thehighest rate of differentiation among unmed-icated female CFS patients and female healthycontrols, without misclassifying the subjectswith major depression as CFS. “CFS patientsmanifest patterns of functional brain couplingthat differ from those of normal controls. Sucha difference of CFS brain physiology may helpexplain known differences in cognition, mem-ory, sleep, and affect that afflict CFS patients.”Chief among the distinguishing factors werethose involved in the brain’s temporal lobefunction. (BMC Neurology, July 1, 2011)

On our new website, Research1st, we regularly update the progress being made in understanding CFS through engagement by researchers in a wide variety ofmedical and scientific disciplines and resulting publications in diverse journals. Here are some of 2011’s top journal highlights. The alerts you tomore in-depth information about this study on Research1st.

OtherGynecologic Problems Common: Researchersat the U.S. Centers for Disease Control &Prevention compared gynecological historiesof 36 women with CFS to 48 nonfatigued con-trols. Women with CFS had more gynecologicalconditions, including non-menstrual pelvic pain,endometriosis and amenorrhea. CFS patients hada higher mean number of pregnancies. Seventy-six percent of the women with CFS reportedhysterectomy compared to 55 percent of thehealthy women. Fifty-six percent of the womenwith CFS had one or both ovaries removed,while only 34 percent of healthy controls had thissurgery. (Journal of Women’s Health, Jan. 2011)

Behavioral Therapies Compared: This largestudy compared four treatment approaches in

Impaired Cardiac Function: Julia Newton’sgroup at Newcastle University used a newmethod of assessing the shape, structure andfunction of the heart in this study of 12 CFSpatients and 10 healthy controls. They foundthat compared to controls, “CFS patients havemarkedly reduced cardiac mass and bloodpool volumes, particularly end diastolic vol-ume: this results in significant impairmentsin stroke volume and cardiac output compared

to controls.”(Journal ofInternalMedicine,July 27, 2011;accepted articleapproved forpublication) �

7

641 patients using Oxford, CDC and Londoncriteria for CFS and ME. The study reportedmodest benefits following a six-month courseof cognitive behavioral therapy (CBT) orgraded exercise therapy (GET) compared tospecialized medical care alone or adaptivepacing therapy, based on improvement inself-reported symptom scores. There were nobiological measures taken during the studyto correlate with the results and media reportsgreatly exaggerated the small gains made bysome participants in self-report measures.This study sparked a firestorm within thepatient community and at its boundary withthe media, igniting tensions that sizzled inheadlines through the summer months. Aseries of reports in the U.K. media alleged thatSimon Wessely, one of the study authors, and

researchers who reported negative results inXMRV studies had received death threats froma small number of patient activists. (Lancet,Feb. 18, 2011)

Heritable Predisposition: Utilizing the UtahPopulation Database, researchers searchedlinked medical records for the diagnostic codefor CFS (780.71). They identified 941 personswith a CFS diagnosis for whom there was avail-able geneology data; 811 cases were includedin the assessment. The analysis “shows clearevidence of significant excess familial clusteringand significantly elevated risks for CFS amongfirst, second, and third degree relatives of CFScases. The results strongly support a geneticcontribution to predisposition to CFS.” (BMCNeurology, May 27, 2011)

The name and definition have been debated for decades. Three papers published this summer in quick succession drew attention to both issues.

New M.E. Criteria: A panel of 26 physicians, researchers and teaching faculty led by Bruce Carruthers proposed new criteria for myalgic encephalomyelitis(M.E.) and recommended use of this term and criteria as a replacement for CFS. The criteria propose one compulsory feature – post-exertional neuroim-mune exhaustion (PENE) – plus seven symptoms from three subdivided symptom clusters: neurological, immunological and energy production/transportimpairments. The criteria are intended for clinical and research use and the paper states that the panel is developing Physicians’ Guidelines and anInternational Consensus Symptom Scale for use in these settings. There is sure to be more discussion about the change in both the name and criteria,for both have potentially far-reaching consequences for research, policy and education. (Journal of Internal Medicine, July 20, 2011; accepted articleapproved for publication)

British Study Estimates Rates, Compares Case Definitions: The ME/CFS Observatory conducted a study of ME/CFS in three distinct areas of England todetermine prevalence, incidence and the ability of different definitions to detect ME/CFS (CFS). The prevalence rate of cases meeting the 1994 (Fukuda)definition was 0.19 percent of the population and slightly lower (0.11 percent) for cases meeting the Canadian definition. Prevalence was higher inLondon (urban), among women and among white-British, compared to industrial or rural areas, men or non-white ethnic minorities. The group suggestscombining the Fukuda and Canadian criteria for ascertainment of ME/CFS cases. (BMC Medicine, July 28, 2011)

Case Definition Face-Off: A group of researchers led by Leonard Jason used data-mining techniques to determine which questions were most effective foraccurately identifying cases using two definitions: the Canadian ME/CFS clinical definition (Carruthers, 2003) and the “empiric” definition proposed byCDC in 2005. Their findings show that the Canadian definition selects cardinal features of the illness better than the empiric and is better at discriminat-ing cases from noncases. (Journal of Clinical Psychology, Aug. 5, 2011)

Case Definition

� Served as a peer-reviewer for several CFS-related grant applications and manuscripts.

Presentations and Meetings� Participated in the meeting of collaborators forthe study of XMRV being led by Dr. Ian Lipkin.(Dec. 20, 2010) (See page 9 for more info.)

� Provided an overall summary of research,existing gaps, areas of agreement and needednext steps at the ME/CFS State of theKnowledge Workshop. (April 7–8) (Seepage 10 .)

� Delivered public testimony at the DHHSCFS Advisory Committee meeting, alongwith CEO Kim McCleary and Boardmembers Jennifer M. Spotila, J.D., andAmy Squires. (May 10–11) (See page 10for more info.)

� Gave a presentation on CFS and chaired asession at the 6th Annual TMJ AssociationScientific Meeting on Co-Morbid Conditions.(June 5–7)

� Spoke to participants, volunteers, donors andsponsors about CFS at the second annual 24Hours in the Enchanted Forest. (June 17–19)(See page 11 for more info.)

� Delivered three presentations on biobanking atthe Genetic Alliance 25th Annual Conference.(June 23–26)

� Gave a series of presentations in Sweden,including a half-day seminar with other CFSexperts at the Ministry of Health and a programfor doctoral students at the University of Umea.(Aug. 22–26)

� Provided more than a dozen media interviewsand authored numerous articles for Associationpublications. �

Our scientific director,Suzanne D. Vernon, PhD, hasdedicated the majority of herprofessional career to studyingCFS and bridging gaps in ourscientific understanding of it.It’s more than just an occu-pation for Suzanne, it’s a

personal passion. From the podium at scientificmeetings to the steep and narrow trail at a 24-hourbike race organized to solve CFS, her leadershipof the Association’s research program is recog-nized and lauded by researcher-colleagues,patients and advocates alike. Here is a brief sum-mary of some of ways in which Suzanne has beenorchestrating transformation over the past year.

Sponsored Research Program� Closely monitored grantees’ performancemilestones and outcomes. (See pages 2–3for more information.)

� Developed and widely circulated newRequest for Applications (RFA). (See pages4–5 for more information about the nextphase of funding.)

� Explored various data-sharing platforms andpolicies and other institutions’ policies onintellectual property to foster discovery anddevelopment of promising findings.

� Reviewed Letters of Intent and issued invita-tions and declinations to investigators whosubmitted letters of intent.

� Distributed revised policies and addressedquestions from invited applicants and theirrespective institutions.

� Recruited dozens of qualified reviewers toevaluate the scientific and strategic meritof proposals due Sept. 30.

SolveCFS BioBank� Oversaw the conversion of the collection ofextensive medical history and clinical datafrom BioBank participants from a paper-based system to a secure online system. (Seepage 4 for more information about the plansto expand the SolveCFS BioBank.)

� Completed the first collaborative study usingBioBank resources, data for which is beinganalyzed and prepared for publication.

� Received two new applications to utilizeBioBank resources; one has been approvedand one is pending review by the MedicalResearch Advisory Committee.

Other Collaborations� Served as a member of the NIH ME/CFSState of the Knowledge Workshop planninggroup. Participated in several group discus-sions as follow-up to the need for acentralized data-sharing platform.

� Participated in two XMRV-related workinggroups; CEO Kim McCleary participates intwo other XMRV-related working groups.

� Consulted with a biotech company to developa biomarker proposal in response to theDepartment of Defense CongressionallyDirected Medical Research Program(CDMRP). (See page 10 for more infor-mation about the CDMRP.)

� Developed five research funding proposalssubmitted to other institutions, all of whichare collaborations with other investigatorsand organizations.

� Helped identify clinical collaborators for aPhase II clinical trial of a promising therapybeing planned by an academic center.

Hi-Fi Sci-Di: Dr. Suzanne Vernon Orchestrates High-Fidelity Research

The X FactorTwo years ago, a gammaretrovirus calledxenotropic murine leukemia virus-like virus(XMRV) was linked to CFS with a high-profilestudy published in Science by a team ofresearchers from the Whittemore PetersonInstitute (WPI), National Cancer Institute(NCI) and Cleveland Clinic. Today, this studyby Vincent Lombardi et al. remains the only oneto have shown an association between XMRVand CFS. Research groups in six countries havetested samples from CFS patients and published15 papers that cast doubt on the original data.Through more than 170 publications aboutXMRV, researchers have documented a betterunderstanding of its origins, life cycle and otherproperties, yet no links to human disease havebeen firmly established.

Recent StudiesWhile several of the early follow-up studiesinvolving samples from CFS patients were small,used broader criteria to define CFS or had otherlimitations, two major studies published in May2011 addressed many of the criticisms. The firstwas from Clifford Shin et al., published May 4 inthe Journal of Virology. Konnie Knox et al. pub-lished results in Science on May 31. Both groupstested samples from CFS patients who had testedpositive at WPI, yet neither group found evidenceof the virus in those samples or others they testedfrom well-characterized patients using multipledetection methods. Both studies attracted consid-erable media attention that kept CFS and XMRVin headlines for most of May and early June.

Another group at NCI led by Tobias Paprotkareported in the same issue of Science that XMRVoriginated through a laboratory recombination oftwo mouse viruses in the prostate cancer cell lineCWR22Rv1. The recombination event occurredbetween 1993 and 1996. This evidence makes itunlikely that XMRV will be shown to be the solecause of CFS, which certainly existed beforethese dates. The XMRV sequences submitted byWPI to the public DNA sequence database are98–100 percent identical to VP62, an XMRVclone derived from 22Rv1 and used by WPIand the Cleveland Clinic.

The other piece of evidence weighing againstXMRV as a human pathogen are multiple reportsof contaminants with mouse DNA in laboratoryreagents, supplies and equipment that can showfalsely positive results in tests for XMRV andother murine leukemia virus-like viruses (MLVs).Four papers published on Dec. 20, 2010, inRetrovirology drew considerable attention to the

issue of contamination. The twoCFS papers published in May(described above) reported spe-cific sources of contaminantsthat were encountered in theirstudies. Information posted toNCI’s website in early Junestates, “a sample of the XMRVviruses reported in the 2009article has been cultivated frompatient samples and was ana-lyzed at NCI. In contrast to theoriginal findings, the new datasuggest it is unlikely that theseXMRVs were derived frominfected patients. Instead, likethe other XMRVs that havebeen sequenced, they appearto be laboratory contaminants.” Robert Silvermanof the Cleveland Clinic told the Chicago Tribunein March 2011 that he was “concerned aboutlab contamination, despite our best efforts toavoid it.” His lab is conducting additional experi-ments to test for the possibility. WPI has statedrepeatedly that its tests for contaminants havebeen negative.

By the end of May, doubts about the originalreport had grown so strong that the editor ofScience, Bruce Alberts, requested the authorsretract the original paper. They declined to doso, stating it was premature. On May 31, Albertsissued an “Editorial Expression of Concern”that is now tagged to the paper pending theoutcome of two large multicenter studies beingfunded by the National Institutes of Health(NIH) (see below).

Supporting evidence for gammaretrovirus associ-ation with CFS has come from two groups whohave reported finding sequences consistent withthe larger family of gammaretroviruses, but notXMRV specifically. The first team, from theFood and Drug Administration (FDA), NIH andHarvard Medical School, published its findings inAugust 2010 in the Proceedings of the NationalAcademy of Sciences (Shyh-Ching Lo et al.).Testing stored samples collected in 1993 for astudy looking for mycoplasma, Dr. Lo found32 of 37 samples from CFS patients positive forMLV sequences. Eight patients from that cohortprovided fresh samples and seven of those testedpositive again. None of the researchers involvedin this study has reported any further data.However, two papers published this summer bygroups working independently reported that thesequences obtained from the two time pointswere not consistent with evolutionary changes.

The other group, led by Cornell Universityresearcher Maureen Hanson, has presented data atmeetings, but its findings have not yet been reportedin the literature. The WPI has presented positivedata from a study of patients in the U.K., but thathas not yet been published, either. News aboutother unpublished data has circulated through thecommunity and some have charged that positivestudies are being unfairly declined by journals,but no specific incidents have been made public.

Clarity Ahead?To bring greater clarity to the issue, NIH issupporting two studies that involve some of thelabs that have published conflicting data.

The first is being coordinated by the NationalHeart, Lung and Blood Institute and is known asthe Blood XMRV Scientific Research WorkingGroup study (SRWG). It is a four-phase studydesigned to evaluate XMRV detection assays inanalytical and clinical samples and to make an ini-tial estimate of XMRV prevalence in blood donors.

� Results from Phase I were reported in July2010 at a meeting of the FDA’s Blood ProductsAdvisory Committee (BPAC). They showedthat six participating labs (CDC, Gen-Probe,NCI-Drug Resistance Program, WPI andFDA-Lo and FDA-Hewlett) had comparablesensitivity in their testing methods using codedanalytical samples spiked with XMRV.

� Phase II results were presented at a BPACmeeting in December 2010. The presentationwas repeated days later during a webinarhosted by the CFIDS Association. (The record-ing is available on our YouTube channel foron-demand viewing.) In Phase II, samples wereobtained from four subjects whom WPI indi-cated were positive for XMRV on multipleoccasions and one pedigreed negative control(tested in Phase I). Samples were collectedin the same manner and then split into threegroups for immediate processing and process-ing after two days and four days to compareresults. Five labs (CDC, Gen-Probe, NCI-DrugResistance Program, WPI and NCI-Ruscetti)tested the samples under blinded conditionsusing the assays from Phase I. Results fromthree labs (CDC, Gen-Probe and NCI-DrugResistance Program) were all negative. WPIhad at least one positive result for three ofthe four XMRV-positive subjects as well asthe negative control. NCI-Ruscetti reportedpositive results for three of four XMRV-positive subjects, as well as the negativecontrol. The results from WPI and NCI-Ruscetti agreed on two of the XMRV-positivesubjects and differed on the other two. Oneof the aims of Phase II was to determinewhether processing time affected testingresults; the data indicated that it did not.

At a Dec. 14, 2010, meeting of the FDA’s Blood Products Advisory Committee (BPAC), the com-mittee heard nine presentations on XMRV research and testimony from several public witnesses.The Committee was asked to vote on the following question: “Do the scientific data support askingdonors about a medical history and/or diagnosis of as a basis for indefinite deferral?” Ninemembers voted “yes” while four voted “no.” The 9–4 vote reflects opinion on the issue of whetherasking a question of blood donors was better than using educational materials to elicit donordisclosure of past/present diagnosis, the process most blood centers had put in place in June 2010.All BPAC members indicated that they agree with the indefinite deferral of patients based on allevidence that it will promote donor and recipient safety. The FDA strongly considers guidance fromits advisory committees when making policy. No date has been provided for a decision by the FDA.

In a special report published in the Apr. 2011 issue of Future Microbiology, Roger Dodd, Ph.D.,vice president, research and development for the American Red Cross, addresses the issue of bloodsafety. He concludes,

“…the issue may perhaps best be analyzed by considering the safety issues relating to ME/CFSseparately from those involving XMRV/MLV. It thus seems reasonable to accept that patients witha past or current diagnosis of ME/CFS should not give blood, both for their own protection and as aprecautionary measure, given the potential associations of chronic viral infections with the disease.”

Blood Safety

VALIDATECFS8

The March 14, 2011 issue of Nature, one of the world’s most prestigiousscience journals, covered XMRV in depth with Ewen Callaway’s “Fightingfor a Cause.”

Predicted Recombinant BetweenPreXMRV-1 and preXMRV-2

It remains to be seen whether XMRV will providethe answers to better methods of diagnosis andtreatment that were heralded in October 2009.There is no question that the original report of anassociation has attracted remarkable scientific tal-ent, increased engagement by health agencies andcreated unprecedented awareness of the devastatingimpact of CFS. No other report among the 5,000+peer-reviewed articles about CFS has attracted thismuch attention or such sustained effort to investi-gate more thoroughly. The debate over XMRVhas been polarizing at times, but there is no longerdispute about whether CFS is worthy of scientificendeavor; that, in itself, is progress. �

expected to wrap up before year-end, delaysin securing required institutional approvals maypush the conclusion of the study into 2012.

Other studies continue as well:� The American Red Cross is collaboratingwith Gen-Probe and Abbott Laboratories totest samples from 10,000 healthy people insix geographic areas. They will also test sam-ples from 120 recipients of blood donationsfrom more than 4,000 donors. Both donorsand recipients will be tested for evidence ofXMRV and MLVs.

� The NCI has evaluated CFS patients who hadbeen previously tested for XMRV at one of itsclinics for a study of the different assays usedto detect XMRV.

� The FDA’s Center for Biologics Evaluation andResearch has conducted a study of the trans-mission and infection processes of XMRV toaddress potential safety concerns in cells usedto produce vaccines and blood products; resultshave been submitted for publication.

� Based on presentations made earlier thisyear at the 18th Conference on Retrovirusesand Opportunistic Infections (March 2011) andthe 15th Conference on Human Retrovirology,HTLV and Related Viruses (June 2011), thereare other reports in the publication pipeline.

In spite of the other conflicting data, it wasdeemed that Phase III would proceed.

� This spring, samples were collected from30 subjects who previously tested positivefor either XMRV or MLV sequences, twopedigreed negative controls and 12 blooddonor controls. Five analytical controls wereincluded in the panel as well. Eight partici-pating labs (CDC, Gen-Probe, NCI-DrugResistance Program, WPI, NCI-Ruscetti,FDA-Lo, FDA-Hewlett and Abbott) testedblinded samples according to approvedprotocols and each has submitted its resultsto the Blood Systems Research Institute fordecoding and analysis. Results will be pre-sented at meetings this fall and submittedto a peer-reviewed journal.

� The need for Phase IV (focused on blooddonors) will be based on the outcome ofPhase III.

The second large study is being sponsored bythe National Institute for Allergy and InfectiousDiseases. W. Ian Lipkin, M.D., of Columbia’sCenter for Infection and Immunity, a renownedpathogen hunter, is coordinating the collectionof samples from 100 well-characterized CFSpatients and 100 matched controls from four sitesaround the country. Samples will be processed,blinded and sent to labs at the FDA (Lo), CDCand WPI. Dr. Lipkin will break the code andreconcile the results. Although the study was

In testimony presented on May 10, 2011,to the federal CFS Advisory Committee, CFIDSAssociation president & CEO Kim McCleary madethe following statement about XMRV:

“The CFIDS Association stands for rigorousresearch that leads to better care for CFSpatients. The results of NIH-supportedresearch into XMRV will provide answersabout whether XMRV is a route to bettercare. We will support the outcome of thosestudies, whichever way they lead. We willcontinue to foster the engagement of scien-tists interested in viral hypotheses and otherwell-reasoned approaches to improvingdiagnosis and treatment.”

9

VIPDx and WPI previously tested 37 of these:� 26/37 XMRV positive� 11/37 XMRV negative

Chart review found 19 of 41 had 2 blood sam-ples drawn on the same day by samephlebotomist; 1 sent to VIPDx, 1 sent to WVRG.� VIPDx detected XMRV DNA in 10/19 samples� WVRG tested the same samples,

0/19 positive

Discrepant findingsprompted new collectionof samples called P2

WVRG results for these 29 samples:� 0/29 positive by RT-PCR on PBMCs

& plasma� 0/29 positive by culture of activated

PBMCs

Sera from 19 CFS patients and 7 healthycontrols was tested for ability to inactivateXMRV and X-MLV:� 26/26 inactivated XMRV and X-MLV

� > inactivation of X-MLV than XMRV

26 tested positive for XMRV in at least one ofthe three virus assays or had XMRV antibod-ies detected by VIPDx or WPI.*

Chemiluminescence immunoassays to detectantibodies to XMRV or other MLVs� 1/60 weak positive but not confirmed by

western blot

26 female, 15 male

20 CFS females9 CFS males

7 healthy controls

This diagram shows the testing of two CFS cohorts for XMRV by Knox et al. asreported in Science.

p1 = 41 archived samples from CFSpatients cared for at the Sierra Internal Medicine

p1 = 29 fresh collected samples from CFSpatients cared for at the Sierra Internal Medicine

60 plasma samples from P1 and P2tested for antibodies Western Blot

(SU protein)Western Blot(cell lysate)

NestedPCR

QuantitativePCR

ELISA(SU protein)

SpinInoculation

SerumPlasma

Genomic DNAExtraction

White BloodCells

White BloodCells

WPICohortn=14

HealthyVolunteersn=200

CFSPatientsn=100

Shin et al., tested 100 CFS patients, 200 matched controls and 14 WPIpatients for XMRV using multiple testing methods, as reported in theJournal of Virology.

As reported by Paprotka et al., in Science, XMRV may have originatedwith a laboratory recombination of two mouse-derived viruses (left halfand right half) in a prostate cancer cell line.

CONNECTCFS10

Introducing Research1st: A New Internet Home for the AssociationOn May 24, we introduced Research1st.com,a new website and blog intended to become aone-stop shop for the most current and reliableinformation about CFS research. The site housesregularly updated information about currentresearch initiatives and another section onfindings from completed studies. A section onmedia coverage makes it easy to track how thepress reports on studies and the evolving scien-tific understanding of CFS. Research1st.comalso features a moderated blog with more than100 posts by staff writers and guest contributors,where comments are welcomed. Posts providein-depth analysis of new study results, confer-ence reports, announcements and perspectives.The site has several search tools to aid in locat-ing material. Research1st.com complements

our main website, Facebook page, Twitter feed,YouTube channel and our monthly e-newsletter,CFIDSLink.

We recognize that many SolveCFS readersdon’t have regular access to the Internet, sowe’ll point you to a few Research1st posts thatyou may want to prioritize:

“XMRV: Trials and Tribulations” |Suzanne Vernon, Ph.D. and KimMcCleary | June 1, 2011Analysis of two studies published in Sciencethat led editor Bruce Alberts to requesta retraction of the original study linkingXMRV and CFS. (More info on pages 8–9.)

“Exercise Challenge Reveals PotentialBiomarkers” | Kim McCleary |June 2, 2011Analysis of the exciting Journal ofMedicine study from Dr. KathleenLight and collaborators, funded bythe Association (see pages 2 and 6).

“The Outs and Ins of OI” |Kim McCleary | June 19, 2011“Is it Anxiety or OI?” |Kim McCleary | June 21, 2011 The first article provides a briefoverview of OI, its diagnosis andmanagement. Based on one of manyexcellent questions posed by read-ers, Kim followed up on the overlapof OI symptoms and anxiety.

“From the CEO’s Desk: What Can WeLearn?” | Kim McCleary | July 8, 2011Kim looks at the recent debate over Avastinand lessons from HIV/AIDS advocacy formessages about the often tense boundariesbetween patients, researchers, physiciansand regulators.

“Oxidative Stress and MitochondrialDysfunction: Key Players in CFS?” |Dikoma Shungu, Ph.D. | July 21, 2011Dr. Shungu refers to two classic papers thatpoint to clues.

“Shedding Light on Biomarkers” |Alan Light, Ph.D. | Aug. 2, 2011Dr. Light defines the term “biomarker” anddescribes how biomarkers are evaluated.

“I Can’t Brain Today: I’ve Gotthe Dumb” | Katrina Berne, Ph.D. |Aug. 9, 2011Dr. Berne describes the cognitive dysfunc-tion she experiences and offers tips for howto compensate.

“Doc Talk: Filling the Information GapBetween CFS Clinicians and Patients” |Lucinda Bateman, M.D. | Aug. 22, 2011Dr. Bateman offers insights and suggestionsfor how to bridge communication.

Throughout this issue of SolveCFS, look forthe symbol; it signifies expandedinformation available on Research1st. �

Federal Agency UpdatesNIH Convenes ExpertsThe National Institutes of Health (NIH) hostedthe ME/CFS State of the Knowledge Workshopon April 7–8, 2011. Held on the NIH campus,the workshop brought together subject matterexperts to discuss epidemiology, etiology,pathophysiology, diagnosis and treatment.Workshop panelists helped identify gaps inknowledge and opportunities for advancing bio-medical research. NIH Director Francis Collinsaddressed the meeting and several other topDepartment of Health and Human Services andNIH staff attended all or part of the two-daysession. Secretary of Health Kathleen Sebeliusexpressed her support in a letter sent to the100+ workshop participants.

The meeting was webcast live and the record-ings have been archived for on-demand viewing.Jennie M. Spotila, J.D., participated by webcastand prepared a summary posted to Research1st.

The NIH issued a formal summary ofthe proceedings in August. You can find linksto these and other meeting resources atwww.cfids.org/SolveCFS/smr-fall2011.asp

The Workshop was planned by the Trans-NIHME/CFS Working Group under the leadershipof Dennis Mangan, Ph.D., and a steering

committee comprised of the followingvolunteers appointed by NIH: Pat Fero; KenFriedman, Ph.D.; Leonard Jason, Ph.D.; NancyKlimas, M.D.; Mary Schweitzer, Ph.D.; andSuzanne Vernon, Ph.D.

CFS Advisory CommitteeRecommendations and NominationsThe CFS Advisory Committee (CFSAC) to theDepartment of Health and Human Servicesmet May 10–11, 2011, to hear agency updatessubcommittee reports and public testimony

and to make policy recommendations.Three recommendations were made (excerptedfrom the official record):

1. The CFSAC considers CFS to be a multi-system disease and rejects any proposalsto classify CFS as a psychiatric condition inUS disease classification systems. (NOTE:no disease classification system under HHS’control proposes to move or to include CFSin or among psychiatric conditions.)

2. The April 2011 NIH State of KnowledgeWorkshop identified a number of gaps inwhat is known about the illness. CFSACrecommends that ME/CFS research receivefunding commensurate with the magnitudeof the problem and that the NIH (and/orother appropriate agencies) issue an RFAspecifically for ME/CFS.

3. CFSAC asks that HHS organize a workshopto engage experts in disability assessment, theoutcome being a document useful to patientsand adjudicators which could contribute to amore efficient and fair disability process.

The terms of three CFSAC members will endin April 2012. In August, the Associationresponded to an open request for nominations

with the following recommendations: RogerDodd, Ph.D. (Vice President for Research andDevelopment, American Red Cross); AlanPocinki, M.D. (Clinical Associate Professor,George Washington University Medical Center);Charles MacBrayer Sasser, J.D. (FoundingPartner, Sasser Law Firm) and Suzanne D.Vernon, Ph.D. (Scientific Director, The CFIDSAssociation of America).

Department of DefenseRecognizes CFSThe Department of Defense’s CongressionallyDirected Medical Research Program (CDMRP)included CFS in itspriority topics forthe first time infiscal year 2011.The Associationadvocated for itsinclusion during the FY11 federal fundingcycle. This recognition enables researchersto compete for funding under this $50 millionprogram, although applications must success-fully pass peer review. The Association isaware of several groups that submitted CFS-related applications to meet the July 5, 2011,deadline. �

Building Awareness and Deepening UnderstandingAward-winning author and CFS patient Laura Hillenbrand is again receiving rave reviews for her new book, titledUnbroken, released on Nov. 16, 2010, by Random House. She tells the true story of World War II bombadier LouisZamperini in this “testament to the resilience of the human mind, body and spirit.” Sinceits release, the book has stayed at or near the top of multiple bestseller lists and has won orbeen nominated for several awards. It has also attracted international media coverage,

focusing attention on Laura’s owntriumph of mind, body and spirit.“The Today Show,” TIME maga-zine, the New York Times, USAToday, the Washington Post, ELLEmagazine and Sports Illustratedare just a few of the outlets thathave helped inform the publicabout Laura’s courageous battle.

Pulitzer-Prize winning journalist Amy Dockser-Marcus was among the first to cover the research that connectedCFS to XMRV. In the nearly two years that have passed, she has distinguished herself by sticking with the storyand expanding the coverage to include other aspects of CFS research, writing more than 30 articles about CFS forthe Wall Street Journal and its Health Blog. March 2011 was a big month. On March 5,CFS filled two pages of the Journal’s Review section with an article titled, “The Puzzleof Chronic Fatigue.” Amy traveled to Lyndonville, NY, to trace Dr. David Bell’s longjourney caring for patients with CFS. On March 12, her article, “AmidWar on a Mystery Disease, Patients Clash With Scientists,” shared thefront page of the paper with news of the tsunami in Japan. It explorestensions that have deep roots going back to the name of the conditionitself, a poorly funded federal research effort that has too often strayedto behavioral and psychosocial issues and decades of neglect by themedical community. “Unlocking Chronic Fatigue Syndrome,” ran inthe paper on March 22. It featured an essay by patient Molly J. Billingsabout her life with CFS.

The Institute of Medicine (IOM) released a lengthy report, “Relieving Pain in America: ABlueprint for Transforming Prevention, Treatment, and Research,” on June 29, 2011. A pressconference and a statement from 32 organizations (including the CFIDS Association of America)attracted considerable media attention to the 116 million Americans who experience chronicpainful conditions, and its high economic toll, costing the nation up to $635 billion annually.TIME, US News & World Report, Reuters and hundreds of other news outlets covered the story.The report includes several pages of policy recommendations. In particular, the IOM hasrecommended that “the Department of Health and Human Services develop a comprehensiveplan with specific goals, actions, and timeframes…Given the burden of pain in human lives,dollars, and social consequences, relieving pain should be a national priority.”

The CFIDS Association is pleased to announce that it has been approved to join patientINFORM, a collaboration ofmedical publishers, health organizations, medical societies and health information professionals. Through the uniquepatientINFORM partnership, participating publishers allow qualifiednonprofit health organizations to provide access to the full text ofjournal articles without a subscription. The patientINFORM logo is likea seal of approval given to top websites that seek to link consumers withthe most current, reliable information available about a particular condition. The CFIDS Association joins top-ratednonprofits including the American Heart Association, the American Diabetes Association and the Lupus Foundationplus publishers like Nature Publishing Group, AAAS (Science), Elsevier and Wiley-Blackwell. We are in the processof updating our Research1st site to add full-text links to research study summaries and analyses of articles publishedin participating journals.

Supporting the CauseThe Association welcomes to its Board of Directors Kevin Frick, co-founder and general partnerof Serent Capital. Kevin is a graduate of Stanford University’s M.B.A. program and graduatedsumma cum laude with a B.S. in electrical engineering from University of Michigan. Before found-ing Serent Capital, Kevin was a partner in McKinsey & Company’s Palo Alto office. Kevin lives inSan Carlos, CA, with his wife Michelle Thies. They have been actively pursuing a solution to herCFS symptoms for more than 10 years. We also extend tremendous gratitude to retiring directorsKatrina Berne, Ph.D., and Dimitris Papanicolaou, M.D. Trina served from 2004 until early this year,most recently leading the Board’s Nominating Committee. Dr. Papanicolaou joined the Board in 2005 and now serveson the Scientific Advisory Board.

The CFIDS Association won $25,000 by placing 23rd among the top 100 organizationscompeting in the Chase Community Giving contest on Facebook in May. Funds will supportthe Association’s research program.

The second annual “24 Hours In the EnchantedForest: A Race to SolveCFS” was held June 18, 2011,in McGaffey, NM. The event raised more than $10,000for the Association’s research program. Claudia

Goodell, who has had CFS since 1985, founded this endurance cyclingevent in 2010. This year’s event attracted about 40 percent more racersand next year’s event promises to be even larger. Thanks to Claudia, theSolveCFS Team (which included our scientific director Suzanne Vernon,Ph.D., and family members) and all the racers and volunteers who madeit a success! Check out links on our website to an action-packed eventvideo made by CFS patient Ken Holmes and a slideshow of photos takenby Mountain Flyer Magazine photographer Brian Leddy. �

The CFIDS Associationof America

BOA RD O F D I R E C T O R S

Adam LesserSan Francisco, CAChairman

Amy DivineBoulder, COVice Chairman

Jennie Spotila, J.D.King of Prussia, PASecretary

Bruce AllshouseNew Castle, DETreasurer

Christoph Bausch, Ph.D.St. Louis, MO

Diane BeanBethesda, MD

Vicki Boies, Psy.D.Chicago, IL

Stuart Drescher, Ph.D.Salt Lake City, UT

Kevin FrickSan Carlos, CA

K. Kimberly McClearyCharlotte, NCPresident & CEO

Robert RaidtRiver Forest, IL

Brian SmithChicago, IL

Amy SquiresAlexandria, VA

Patrick VenetucciPark Ridge, IL

P R O F E S S I O NA L S T A F F

K. Kimberly McClearyPresident & Chief Executive Officer

Kristina P. HopkinsChief Financial Officer

Suzanne D. Vernon, Ph.DScientific Director

Sara L. CollinsPublic Relations & Events Manager

Ashley A. ComstockMajor Gifts Officer

Kim A. AlmondOperations & Network Administrator

Gloria E. SmithOffice Manager

C ON T A C T I N F O

The CFIDS Association of AmericaPO Box 220398Charlotte, NC 28222-0398

E-mail: cfids@cfids.orgWebsites:www.cfids.org and www.Research1st.comResource line: 704-365-2343Fax: 704-365-9755Facebook: www.facebook.com/cfidsassnTwitter: @PlzSolveCFS YouTube: www.youtube.com/solvecfs

Web home for this issue of SolveCFS:www.cfids.org/SolveCFS/smr-fall2011.asp

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News Briefs

TRANSFORMCFS12

For 24 years, the CFIDS Association has steadfastly committed to making CFS widely understood, diagnosable, curableand preventable. We have evolved to meet new challenges and adapt to changing realities. Now, as the vast majorityof our supporters have urged, we’ve narrowed our focus to research. The preceding pages of this issue of SolveCFSreport on progress in advancing our new research-focused strategy and describe how we intend to transform theresearch landscape.

Your gifts have sustained this organization and we present a new opportunity to spur the next phase of vigorous growthand deepening impact.

In science, catalysts are substances that change the rate of chemical reactions. “Positive” catalysts speed a particular reaction. We are seeking at least 200individuals, families, foundations and corporations to help the Association transform CFS research by donating $10,000 or more to a new fund that will speeddiscovery and transform the way that CFS research is conducted. This $2,000,000 sum will allow us to immediately execute plans for the expanded researchactivities described on pages 4–5.

There are three ways you can join other Catalysts to make this goal a reality:

Make a gift or pledge of $10,000 or more with special recognition and benefits at the Gold ($10,000-$24,999),Platinum ($25,000-$49,999), Palladium ($50,000-$99,999) and Rhodium ($100,000+) levels of giving.

Engage family, friends, support group members and others to join with you in making a combined donation of$10,000 or more. We can provide tools to help you prepare a fundraising letter to share with your contacts, set upa Facebook cause or host a local event in support of THECatalystFUND.

Help us secure a special matching grant. Two donor families (who wish to remain anonymous) have pledged upto $75,000 to match a pool of smaller donations so that gifts of any size (up to $10,000 each) help us build towardthe $2,000,000 goal and engage as many supporters as possible in THECatalystFUND. This challenge grant has aDec. 31, 2011 deadline.

Catalysts at all donation levels will be provided exclusive updates from Association leaders, members of the Association’s Scientific Advisory Board and funded inves-tigators. Web-based programs offered only to Catalysts will help keep you personally informed about progress being made across the research field. In addition,Catalysts will receive special recognition in Association publications and events. (Anyone who wishes to remain anonymous is welcome to do so.)

In 2012, we will host a special event marking the Association’s 25th year of service where we will honor Catalystsand members of the President’s Circle, a group of extraordinary individuals whose lifetime gifts to the organizationexceed $50,000. Further details about this gathering will be provided early in the new year.

We are delighted to announce that within days of sharing the newsof the creation of THECatalystFUND with just a few of our mostenthusiastic supporters, a rapid reaction was generated and giftstotaling $192,000 were provided to speed the Fund’s growth. That’sthe power of catalytic action! We’ll share Catalyst profiles andupdates on the $2,000,000 goal through the fall and into winter.

We invite you to become a Catalyst. Gifts of every size are neededand will be gratefully recognized as part of THECatalystFUND.Please use the enclosed envelope to make your gift today, callAshley Comstock at 704-364-0016 ext. 101, or make a secure giftonline at www.cfids.org.

Thank you for your generous support and for considering this unique opportunity tohelp us transform CFS research!

Become a Catalyst to transform research.

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T H E C F I D S A S S O C I A T I O N O F AM E R I C A

Our Mission:For CFS to be widely understood, diagnosable, curable and preventable.

Our Strategy:To stimulate research aimed at the early detection, objective diagnosis and effectivetreatment of CFS through expanded public, private and commercial investment.

Our Core Values:To lead with integrity, innovation and purpose.

We invite you to becomea Catalyst. Gifts of everysize are needed to reach

our $2 million goaland will be gratefullyrecognized as part of

THECatalystFUND.

Did You Know?

Gold, platinum, palladium and rhodium are metalsrequired in many catalyticreactions. Rhodium is oneof the rarest preciousmetals and is the most

costly on earth.