Here are some of the most exciting CFS research initiatives happening today, with links to more information. The CFIDS Association of America is proud to have invested more than $5 million in research since our founding in 1987, while also hosting or co-sponsoring research conferences, symposia and meetings. Learn more about our Sponsored Research Program.
Insights into the biology of CFS, as published in the scientific literature, are described at CFS Research Findings. Check out the Research1st blog for posts about other research discoveries. The blog’s tag cloud can help you locate information on specific topics of interest.
There are many opportunities for CFS patients to participate in clinical studies. You can find a list of some of them here, as well as other places to search for additional studies enrolling patients.
Research-oriented conferences, meetings and workshops provide researchers, clinicians, patients and other stakeholders with opportunities to exchange information and hear about the latest data and discoveries. We regularly update our list of upcoming events.
If you have questions, we’ll do our best to answer them via our blog, FAQs, CFIDSLink (our free monthly e-newsletter) and other information posted on this site.
XMRV & OTHER MLVs
CFS has been linked to a family of murine leukemia virus-related viruses (MLVs), including xenotropic murine leukemia virus-related virus, or XMRV. High-profile studies have expanded research interest and sustained media interest in this potential association, the role of infectious agents in CFS and immune system abnormalities. We’ve followed the research closely since the first report in Science on Oct. 8, 2009, by Lombardi et al. We regularly update a detailed overview of the research and developments and a resource list of all the journal articles, media articles and recordings of presentations.
On May 4, 2011, the most comprehensive follow-up study of XMRV was published in the Journal of Virology by Shin et al. This study used multiple testing methods on freshly collected samples from 100 well-characterized clinic patients, 200 healthy volunteers from the same geographic area and 14 patients who had previously tested positive for XMRV by investigators at the Whittemore Peterson Institute (WPI). The team, led by senior author Ila Singh, PhD, processed, tested and analyzed all samples in an identical fashion. In spite of these measures and every hope of obtaining a positive result, they could not detect XMRV or polytropic MLVs in any of the samples and therefore could not confirm the link between this family of retroviruses and CFS. Of note is that the study followed a template published in the Nov. 3, 2010 issue of Viruses by Dr. Singh that suggests a definitive study of retroviral sequences in CFS. “The Iteration of X” is an analysis of this study prepared by the CFIDS Association’s scientific director and CEO. Publication of this study attracted coverage by the Wall Street Journal, ScienceInsider (Science magazine), Nature NewsBlog (Nature magazine), Los Angeles Times, Chicago Tribune and other outlets.
Two studies published in Science on May 31, 2011 add to the mounting number of publications that challenge the reliability of the initial report. The first study, “Recombinant Origin of the Retrovirus XMRV,” by Tobias Paprotka et al. builds on presentations made in March 2011 at the 18th Conference on Retroviruses and Opportunistic Infections (CROI). It provides data to show that XMRV is a laboratory recombinant of two endogenous murine leukemia viruses that arose during the development of a prostate tumor cell line called 22Rv1. The authors conclude that XMRV originated in the laboratory and does not readily infect or pose a risk to humans. This conclusion is supported by a number of published studies that have used serology to look for evidence of an immune response to XMRV infection.
The second study, “No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected,” by Konstance Knox et al. tested newly collected samples from 61 CFS patients diagnosed by Daniel Peterson, M.D. Of the 61, 43 had tested positive for XMRV by the Whittemore Peterson Institute or its commercial laboratory, VIP Diagnostics. This team used a variety of methods to detect XMRV and did not detect XMRV in any of the freshly collected samples. Following on reports from other laboratories, they tested a variety of reagents used to perform polymerase chain reaction and found 9 of 17 to be contaminated with mouse DNA similar to sequences reported by Lo et al. in the Proceedings of the National Academy of Sciences. These two studies, published the same day as an Editorial Expression of Concern from Science’s editor-in-chief Bruce Alberts, were covered heavily by general and science-oriented media outlets including the New York Times, National Public Radio, Scientific American and Nature. The Whittemore Peterson Institute replied to Science in a series of letters, including this one from the senior author of the 2009 paper, Judy Mikovits, PhD.
At an international conference on HTLV and other retroviruses held June 5-8, 2011 in Belgium, eight presentations and 15 posters provided some new data and a forum for discussion of the conflicting findings in the field. Other publications and media coverage from late May through early July are summarized here. The most recent report of XMRV testing of CFS patients examined a cohort of monozygotic twins discordant for CFS using three PCR assays and found no positive PBMC samples. (Jerome KR et al., Diagnostic Microbiology and Infectious Diseases, July 27, 2011.)
Two multicenter studies supported by the National Institutes of Health (NIH) will help bring greater clarity to these issues. The first, known as the Blood XMRV Scientific Research Working Group (SRWG) study, was supported by the National Heart, Lung and Blood Institute (NHLBI). The third and now final phase was completed in August 2011 and results were published in Science on Sept. 22, 2011. In the SWRG’s Phase III study, none of the 19 assays used by nine participating labs was able to distinguish previously XMRV/MLV-positive CFS cases from healthy blood donors or pedigreed negatives on the basis of results for XMRV or the larger family of murine leukemia viruses. The results of the study are further described here and in a webinar with study leaders recorded on Oct. 14, 2011.
The second large study is being coordinated by Ian Lipkin, M.D., at Columbia University and funded by the National Institutes of Allergy and Infectious Diseases (NIAID). Six clinical sites will provide samples from well-characterized CFS patients and matched healthy controls. Coded samples will be tested under blinded conditions by investigators using their own assay methods and Dr. Lipkin will break the code. The laboratory investigators involved in the study include Dr. Judy Mikovits, Dr. Francis Ruscetti (NCI), Dr. Shyh-Ching Lo (FDA) and Dr. Willam Switzer (CDC). Sample collection for this study is nearly complete. The overall study is due to be completed in 2012.
Recent twists in the XMRV story have attracted even more attention to the controversy and there have now been more than 20 studies published that have not been able to confirm the association of XMRV and MLVs to CFS. A pair of retractions issued just before and just after the 2011 Christmas holiday removed the only two published reports linking these viruses from the record. In its Dec. 23, 2011 issue, Science editor-in-chief Bruce Alberts retracted the 2009 publication by Lombardi et al. On Dec. 26, 2011, the authors of the 2010 PNAS publication retracted their study. There have been no announced changes to plans to proceed with the Lipkin study.
OTHER RESEARCH
On Oct. 19, 2011 results of a double-blind placebo-controlled phase II clinical trial of rituximab were published in PLoS ONE. The study was small, with just 15 CFS patients in each arm, but it showed promising results. 67 percent of the patients treated with rituximab, a monoclonal antibody, showed improvement after two infusions given two weeks apart, compared to 12 percent of those who received placebo. Rituximab is approved for use in certain cancers and rheumatoid arthritis. It is one of manufacturer Roche/Genentech’s “blockbuster” drugs. The study attracted attention from media around the world and resulted in an apology from Norway’s Directorate of Health for the poor care that patients with CFS have received in the country’s health care system. Two additional open-label phase II studies are now under way and the team at Haukeland Hospital in Bergen (Norway) is working with other centers to design a larger phase III study.
An international panel of 26 researchers, physicians and teaching faculty has published new criteria for myalgic encephalomyelitis (ME) in the Journal of Internal Medicine ahead of print on July 20, 2011. The panel recommends use of the term ME and the new criteria as a replacement for CFS in research and clinical settings. The criteria propose one compulsory feature — post-exertional neuroimmune exhaustion (PENE) — plus seven symptoms from three subdivided symptom clusters: neurological, immunological and energy production/transport impairments, summarized here. 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. A study published a week later in BMC Medicine used three case definitions to identify ME/CFS cases in three populations of England. Based on their analysis, the authors recommend using both CDC-1994 definition (for CFS) and Canadian definition (for ME/CFS) to strengthen research studies.
The National Institutes of Health (NIH) hosted the ME/CFS State of the Knowledge Workshop on April 7-8, 2011. The workshop brought together subject matter experts to discuss multiple aspects of ME/CFS, including epidemiology, etiology, pathophysiology, diagnosis and treatment. The workshop panelists helped identify gaps in knowledge and opportunities for advancing biomedical research. NIH Director Francis Collins addressed the meeting and several other top Department of Health and Human Services and NIH staff attended all or part of the workshop. Secretary Kathleen Sebelius expressed her support in a letter sent to workshop participants. Read a summary of presentations. The NIH has also produced a report on the meeting.
The Department of Health and Human Services (DHHS) CFS Advisory Committee (CFSAC) meets twice a year to make recommendations about research policy to the Secretary of Health and Human Services. At its meeting on Oct. 12-14, 2010, the first day was dedicated to a review of key scientific findings. The committee met most recently on May 10-11, 2011 and Nov. 8-9, 2011. Agendas for, minutes of and presentations from past meetings are archived on the DHHS site. DHHS recently solicited nominations for terms of three members that end in early 2012. The CFIDS Association nominated four individuals to serve.
NEW RESEARCH INITIATIVES
On Dec. 21, 2011, the Medical Research Council (UK) announced awards totaling $2.5 million (USD) for five new projects to investigate the mechanisms and underlying biological processes involved in CFS/ME.
Nova Southeastern University (NSU) announced on Dec. 12, 2011 that Dr. Nancy Klimas would join its faculty to launch the Institute for Neuro Immune Medicine within its College of Osteopathic Medicine. Dr. Klimas’ move from the University of Miami comes after 27 years of service, but she saw an opportunity to combine her clinical and research interests under one roof. “It will be a place to coordinate cutting edge thinking and research, train new practitioners, and offer the highest quality clinical care for a hugely underserved population. I am thrilled to partner with NSU in this giant step forward in the field of CFS/ME care and research.”
In the early spring of 2011, British Columbia’s Ministry of Health announced funding of $2 million for a clinical and research study that will help patients with a variety of complex chronic diseases, such as chronic Lyme disease, fibromyalgia and CFS, with screening, diagnosis and treatment. On Dec. 1, 2011, the Provincial Health Services announced that the new clinic will be housed at the British Columbia Women’s Hospital and Health Center. An opening date has not yet been set, but several regional patient groups are involved in the planning. The Vancouver Sun reported about the new clinic on Dec. 6.
On Nov. 18, 2011, the National Institutes of Health issued two new funding opportunity announcements for investigator-initiated applications listed below. Many other funding opportunity announcements of possible relevance to CFS research are listed in the NIH Guide. Enter the keyword search term or a co-morbid condition and then click the Search button.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Etiology, Diagnosis, Pathophysiology, and Treatment (R01)
(PAR-12-032)
Standard R01 receipt dates apply; next receipt date for new applications is Feb. 24, 2012.
A call for R01 applications that propose innovative, interdisciplinary research to examine the etiology, diagnosis, pathophysiology and treatment of ME/CFS in diverse groups and across the lifespan.- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Etiology, Diagnosis, Pathophysiology, and Treatment (R21)
(PAR-12-033)
Standard R21 receipt dates apply; next receipt date for new applications is Feb. 24, 2012.
A call for R21 applications (exploratory/developmental research) that propose innovative, interdisciplinary research to examine the etiology, diagnosis, pathophysiology, and treatment of ME/CFS in diverse groups and across the lifespan.
The U.S. Centers for Disease Control & Prevention (CDC) has entered into contracts with three physician groups: Dr. Benjamin Natelson (Beth Israel, NY); Dr. Nancy Klimas (Miami, FL); and a consortium formed by Drs. Andy Kogelnik (Open Medicine Institute, Calif.), Daniel Peterson (Sierra Internal Medicine, Nev.), Lucinda Bateman (Fatigue Consultation Clinic, Utah), Charles Lapp (Hunter-Hopkins Center, NC) and Richard Podell (NJ). These physicians will provide CDC with clinical expertise from physicians caring for patients with CFS from multiple clinical practices and will obtain standardized clinical, functional and epidemiologic data to ascertain the extent of heterogeneity within and between clinical practices. This information in intended to enable CFS researchers to determine a standardized approach to definition use in clinical diagnosis and management of CFS and improve standardization, integration and sharing of CFS data to benefit research. These contract awards were made in response to a May 2011 solicitation and were announced during the CDC’s agency update at the Nov. 9, 2011 meeting of the CFS Advisory Committee.
A new CFS research and clinical care initiative is getting under way at Mt. Sinai Hospital in New York under the leadership of Dr. Derek Enlander. There has been no formal announcement by the institution yet; a patient meeting held on Nov. 20, 2011 involved Dr. Eric Schadt and Dr. Miriam Merad of Mt. Sinai and promised more extensive collaborations with other researchers and institutions. The effort has been launched with a $1 million gift made by one of Dr. Enlander’s patients.
On Oct. 3, 2011, the CDC announced access to its large data set from the Wichita clinical study of CFS. The data sets were collected during a two-day in-hospital clinical assessment study conducted from December 2002 to July 2003 in Wichita, KS (referred to as Wichita Clinical Study). The study enrolled 227 people and classified them into five study groups. CFS patients were classified using the 1994 case definition (Fukuda et al., Annals of Internal Medicine). There are 32 data sets including demographic, clinical, laboratory, medication usage, cytokines, endocrine, sleep, single nucleotide polymorphism and gene expression data. For more information about the methods by which data was collected and the specific data sets, please visit http://www.cdc.gov/cfs/programs/wichita-data-access/index.html.
The Chronic Fatigue Initiative, launched Sept. 15, 2011, will provide $10 million from the Hutchins Family Foundation to support research and clinical experts at the world’s leading research institutions. The multi-faceted program will begin by funding projects at Columbia University on pathogen discovery and an epidemiology project at the Harvard School of Public Health. The CFI’s mission is closely aligned with the CFIDS Association’s and the two organizations’ approaches are highly complementary.
Research on chronic comorbid pain disorders, including CFS, has been proposed for 2013 funding through the NIH Common Fund, a special program that supports transformative, cross-cutting, trans-NIH programs that affect several disease areas. “Ideas” for Common Fund support are proposed by NIH staff and comments are invited from the public to shape final decisions about which initiatives are established. The title of the idea that specifically includes CFS is “Chronic Pain Conditions: A Transformative Classification for Stimulating Research, Improving Diagnosis, and Personalizing Treatment.”
The CFIDS Association of America issued a new Request for Applications (RFA) on Apr. 6, 2011, soliciting research proposals for studies that will advance diagnostics and treatments for CFS. The RFA was widely circulated in the research community and Letters of Intent were due on June 3, 2011. Full applications have been invited from 27 eligible investigators whose projects were responsive to the RFA and are due on Sept. 30, 2011. Applications will be reviewed for scientific and strategic merit and funding decisions will be based on both evaluations. Awards will be announced in early 2012.
Dr. Daniel Peterson, one of the early pioneers in CFS care and research, has established a new research foundation, Simmaron Research, to make use of his 25 years of experience and an extensive biorepository of biological samples collected from well-characterized patients. The foundation lists two current collaborations with Bond University in Australia and Wisconsin Viral Research. On Dec. 8, 2011, the Mason Foundation (Australia) announced a four-year, $831,037 award to Bond University and its U.S. collaborators.
The Department of Defense’s Congressionally Directed Medical Research Program (CDMRP) included CFS in its priority topics for the first time in FY11. The CFIDS Association advocated for its inclusion during the FY11 federal funding cycle. This recognition gave researchers another potential source of funding, although applications still must successfully pass peer review. Interested investigators were required to submit pre-applications by May 25, 2011. Applications are now under review.
On Mar. 31, 2011, the UK’s ME Association announced that its Ramsay Fund will support new research into the role of transcription factors (complicated proteins that act at a cellular level as a key part of the body’s initial defensive response to harmful stimuli) in ME/CFS. The study is expected to be completed in 2012.
In March 2011, Stanford University launched a Chronic Fatigue Initiative dedicated to studying infection-associated chronic illnesses, including CFS. Under Dr. Jose Montoya’s leadership, the center will provide clinical care and already has several research projects under way.
The Food and Drug Administration’s Office of New Drugs announced on Jan. 26, 2011 that all new applications for CFS treatments will be assigned to the Division of Pulmonary, Allergy and Rheumatology Products. This decision may help streamline review of products that were previously scattered to six different review divisions.
In March 2010, the Association established the SolveCFS BioBank, an integrated patient registry and biorepository that collects standardized medical information and biological samples from individuals diagnosed with CFS and control subjects. The SolveCFS BioBank is operated under the Genetic Alliance BioBank using its cooperative cost-sharing model that translates into a tightly controlled, comprehensive infrastructure to serve the dual functions of a patient registry and biorepository. The cooperative structure utilizes standardized protocols, allows for ethical re-contact of subjects and ensures robust privacy and security protections. Since securing institutional and ethical approval for the SolveCFS BioBank in March 2010, we have enrolled 449 CFS patients and controls, all of whom have consented to provide clinical information and donate biological samples. Through our first collaboration with an industry partner, we collected biological samples from 267 participants who met stringent enrollment criteria for this particular study. Testing of those samples has just been completed and the data is being analyzed and prepared for publication. This project not only adds important knowledge to the literature, but serves as a proof-of-concept for the SolveCFS BioBank structure and the ability to attract new partners to the study of CFS.
The NIH Clinical Center is undertaking a study of CFS patients, especially those who have been tested for XMRV with either positive or negative results. The NIH Clinical Center is the nation’s largest hospital devoted exclusively to clinical research. Teams of researchers, including collaborators at academic institutions, translate scientific observations and laboratory discoveries into new approaches for diagnosing, treating and preventing disease. The study has completed enrollment and testing of samples is currently being completed. Results will be submitted for publication.
The Institute of Medicine issued a consensus report on June 29, 2011 on the current state of pain research, care, and education with recommendations for an integrated strategy to address the human suffering and economic toll it takes. Two public meetings held on Nov. 22, 2010 and Jan. 4, 2011 were attended by representatives of the Chronic Pain Research Alliance (formerly the Overlapping Conditions Alliance) and testimony was presented based on recommendations included in the Alliance’s report issued in 2010, “Chronic Pain in Women: Neglect, Dismissal and Discrimination.” In early 2011, the committee sought public comment on barriers to pain care and groups that may not be adequately treated for pain. More than 2,000 individuals submitted comments, which helped shape the report in addition to extensive research. The report, “Relieving Pain in America: Transforming Prevention, Care, Education and Research,” includes recommendations for immediate and long-term corrective action. Watch the June 29 IOM press conference.
The Institute of Medicine and Department of Health and Human Services hosted The Health Data Initiative Forum on Thursday, June 9, 2011 to accelerate momentum for the public use of data and innovation to improve health. The Forum builds on the success of The Community Health Data Initiative Forum: Harnessing the Power of Information to Improve Health, held in June 2010. It included a number of fast-paced demonstrations that present a range of tools and applications developed using health data, a series of discussion sessions, and a data and apps exposition where participants can interact with featured innovators, learn more about available data, and identify opportunities to expand upon current efforts.
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