Solve ME/CFS Initiative 2014 Webinar Series

July 8, 2014

Workplace-WebinarBeginning in July and continuing through year-end, the Solve ME/CFS Initiative (SMCI) will be bringing you a free, monthly webinar series. Anyone that is interested can RSVP to participate live. Each webinar will be recorded and posted to our website and YouTube channel within a week of the live date, so if you miss it, don’t worry! You can still have access to the great content at your convenience.

Read more about the series and RSVP today!

 

Suzanne

Research Institute Without Walls – Progress and Promise

HELD on Thursday, July 31, 2014
Video Link

Suzanne D. Vernon, Ph.D., scientific director of the Solve ME/CFS Initiative will provide an update on the work being conducted through our Research Institute Without Walls. Participants can also expect to learn more about how the SolveCFS Biobank works and is attracting some of the brightest investigators from the best institutions to ME/CFS research.  You will leave with an understanding of what makes the SolveCFS BioBank unique, how to get enrolled and what to expect when you participate.  Vernon will also provide a sneak peek at some of the types of research being conducted on samples using the SolveCFS BioBank.

 

McGowan

Investigator Report: Epigenetics of ME/CFS

Thursday, August 21, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Patrick O. McGowan, Ph.D., is one of the Solve ME/CFS Initiative 2011 funded investigators.  McGowan is an assistant professor in the Department of Biological Sciences, University of Toronto at Scarborough.  He will talk about his latest results from our grant funding.  McGowan used blood samples from the SolveCFS BioBank to identify the chemical modifications (e.g., methylation) to the DNA that is different in ME/CFS patients compared to healthy people.  This type of research will help explain the immune dysfunction of ME/CFS.

 

Dane-Cook

Investigator Report: Deciphering Post-Exertional Malaise

Thursday, September 18, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Dane B. Cook, Ph.D. is assistant professor of Kinesiology at the University of Wisconsin, Madison.  Cook is one of the Solve ME/CFS Initiative’s 2011 funded investigators.  Cook will describe the system biology approach his team is taking to provide a clear picture as to what causes post-exertional malaise.  This is critically important research for ME/CFS because as Cook notes, “You can’t begin to fix a problem like post-exertional malaise until you can understand its underlying cause.”

 

unutmaz

Investigator Report: Decoding the Human Immune Response

Wednesday, October 1, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Derya Unutmaz, MD, is Professor of Microbiology, Pathology and Medicine at NYU Langone Medical Center.  Unutmaz is using samples from the SolveCFS BioBank to understand the “Good, Bad and Ugly” aspects of the immune response in ME/CFS.  Unutmaz hypothesizes that a disproportionate immune response leads to damage in ME/CFS.   He will describe what the immune signature of ME/CFS looks like compared to a healthy immune response.

 

PeterRoweInvestigator Report: Neuromuscular Strain in ME/CFS

Thursday, October 23, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot - Click HERE

Peter Rowe, MD, who directs the Chronic Fatigue Clinic at Johns Hopkins Children’s Center, will describe some novel observations about restrictions in range of motion in the limbs and spine in those with ME/CFS. Many affected individuals have restricted movements and increased mechanical tension in nerves. Applying a further mechanical strain to the nervous system can provoke increased symptoms in some patients. These concepts are starting to help explain the pathogenesis of some symptoms and neurological abnormalities in the illness—not only how they might arise but also how we might treat them more effectively.

 

 

November and December webinars to be announced at a later date.

 

 

Same Mission | New Name

May 30, 2014

Solve ME/CFS Initiative

We’re delighted to announce that The Solve ME/CFS Initiative has a new name – the Solve ME/CFS Initiative.   While our name has changed, our mission steadfastly remains the same:  We will make ME/CFS understood, diagnosable and treatable.

Why the change?  We recognize the many changes in our organization and our illness space since the organization was first named so long ago in 1987.  While the name of our illness continues to be controversial, “ME/CFS” better reflects today’s understanding. And we believe that the word “initiative” (defined as ‘leading action’), expresses our strong commitment to funding ground-breaking research.

Since our organization was founded and named in 1987, we have been the leading organization focused on this illness.  Over the years, we’re proud of our remarkable advances regarding this controversial and misunderstood disease.

  • Under the 22-year leadership of Kim McCleary, the organization’s first CEO, the Association played an integral part in developing a policy ruling for the Social Security Administration that recognized CFS as a disabling condition.
  • We are the leading private funder of ME/CFS research, directly funding $5.5 million in ground breaking research which has been leveraged into more than $12 million in additional ME/CFS research.
  • The organization fought to create and continues to advocate to sustain a dedicated federal advisory committee on ME/CFS research and education (CFSAC).
  • We helped expose the misappropriation of $12.9 million in CDC spending, restoring these funds to ME/CFS research.
  • We led the first-ever public awareness campaign for ME/CFS, led lobbying events, organized Congressional briefings and regularly deliver testimony at numerous federal hearings and meetings.

Four years ago, guided by a desire to move into a new era of scientific progress on ME/CFS, the Association made a strategic decision to heighten its focus on research.  Our thinking was simple – the best way to use our precious dollars is toward solving this despicable illness.

Today, led by President and CEO, Carol Head, the organization continues to drive its mission forward – to fund research that will make ME/CFS understood, diagnosable and treatable.  How do we do that? By providing more funding for high-quality ME/CFS studies, fostering increased collaboration among ME/CFS researchers and pushing the federal government to make ME/CFS research a higher priority.  We are working to leverage our experience, relationships and collective knowledge to propel the ME/CFS research field forward. We are a catalyst for scientific advances that translate into better care for ME/CFS patients. We are accelerating ME/CFS research.

As we continue our efforts to make ME/CFS widely understood, diagnosable, and treatable, it is fitting that we have a name that more accurately reflects who we are: The Solve ME/CFS Initiative. We trust that you will continue this journey with us as we work towards a day when ME/CFS is no more.

 

P2P Draft Report Set to be Published, 30 days for Feedback

December 18, 2014

P2P_title On December 9 & 10, 2014, the NIH Office of Disease Prevention held its Pathway to Prevention Workshop for “Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. If you were unable to participate in the meeting or watch the live stream, you can access the video archive HERE.

https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs/workshop-resources#archivedvideocast  P2P_screenshot2

On day 2, our own Dr. Suzanne Vernon spoke to the panel about the importance of the patient perspective and their voice in research in a session they titled  “What Outcomes Represent Improvement, Recovery, Prevention, Benefits or Harm?” You can advance to her presentation at time code 3:46:00

Upon the conclusion of the workshop, the panel began writing their report and recommendations. The draft report will be posted on the workshop website on Thursday, December 18, 2014. Comments will be accepted through Friday, January 16, 2015. 

The Solve ME/CFS Initiative will work with members of its Research Advisory Council and other advisers to issue a response to the report. Many other individual advocates and organizations will be doing the same, including members of the federal CFS Advisory Committee (CFSAC), upon which we play an active role.

The Solve ME/CFS Initiative will publish its reaction and response to the draft report on this blog as soon as it is available. Any stakeholder is also invited to offer their response to the draft report. Please reference the corresponding line number of the report, and submit your comments via:

Email - prevention@mail.nih.gov
Or
Postal mail
Office of Disease Prevention
National Institutes of Health
ATTN: Paris A. Watson
6100 Executive Boulevard, Suite 2B03
Bethesda, MD 20892

 

Read our earlier blog posts about the P2P HERE

$500,000 grant awarded to the Solve ME/CFS Initiative to further epigenetic research

December 15, 2014

We are thrilled to announce that the Solve ME/CFS Initiative (SMCI) has received a one-year, $500,000 Catalyst Research Program Award through the Dr. Ralph & Marian Falk Medical Research Trust. This competitive funding opportunity was designed to support research that leads directly to the development of treatments and cures for diseases for which there are no effective treatments or cures today.

SMCI will partner with Drs. Lucinda Bateman founder and director of the Fatigue Consultation Clinic and Patrick O. McGowan of the University of Toronto to expand the epigenetic study of myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) originally funded by SMCI in 2012. “Epigenetics is really a funnel by which the outside environment interacts with the genome,” explains Patrick O. McGowan, PhD, assistant professor at the University of Toronto and co-investigator on this project. This, in turn, influences how cells work (or don’t work). In research originally funded by SMCI, McGowan found evidence of distinct epigenetic profiles in immune and other physiologically relevant genes in a selected group of female ME/CFS patients.  This award from the Falk Medical Research Trust will allow the team to expand on these original findings and partner with ME/CFS clinical expert Dr. Lucinda Bateman.  Bateman will be the lead clinical investigator to expand enrollment of study participants to include male ME/CFS patients and more female patients. This new study will be substantially expanded to include 300 patients and healthy controls.

The Solve ME/CFS Initiative is targeting its work in order to one day understand ME/CFS at an unprecedented molecular level to guide research and development of new diagnostic tests and better treatments. SMCI will do this through funding and organizing rigorous, expansive, early research to deliver results that lead to the development of new diagnostics, therapies and cures. This grant will allow SMCI to accelerate its work, yet there is still much to be done. The support and participation of many patients, caregivers and loved ones has provided the funds for SMCI’s work thus far and remains critical to the path forward.

 

The Solve ME/CFS Initiative is a 501(3) non-profit organization, whose mission is to make ME/CFS understood, diagnosable and treatable.  Founded in 1987, SMCI is the longest standing organization serving ME/CFS patients by advancing rigorous research.

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Research Digest – December 2014: 10 Important Advances in ME/CFS

December 12, 2014

By Suzanne D. Vernon, Ph.D., Scientific Director, Solve ME/CFS Initiative top10
Dr. Anthony Komaroff, Simcox-Clifford-Higby Professor of Medicine, Harvard Medical School, Senior Physician, Brigham & Women’s Hospital, Boston MA

 

In this year-end blog post and December Research Digest, Dr. Vernon and Dr. Komaroff summarize what they regard as the most important recent advances in our field. They are not listed in any specific order. If noted, SMCI played a role in the discovery.

SMCI-Supported1. There is ample evidence that ME/CFS is a heterogeneous illness. As is true with many illnesses, not every person with the illness has all of the same features.   Now we are able to delineate ME/CFS subtypes using tools that measure phenotype (the ensemble of a patient’s observable and measureable signs and symptoms) and genotype (the inherited genetic code and gene expression). By objectively identifying subtypes, researchers are able to study groups of patients that are similar: this increases the likelihood of identifying biomarkers and of targeting treatment.

 

SMCI-Supported2. Many studies now have demonstrated that people with ME/CFS suffer from oxidative stress.  Oxidative stress occurs when the damaging effects of reactive oxygen species (free radicals) are not taken care of by antioxidant defense mechanisms. In other words, oxidative stress occurs when too many free radicals are produced, or not enough antioxidants are produced, or both.  Prolonged oxidative stress can damage cells and the structures inside cells that affect energy production and cell signaling.  Evidence for oxidative stress in ME/CFS has been found in the brain, as reflected by increased levels of lactate.  Oxidative stress more generally throughout the body is reflected by increased lipid peroxidation—which is caused when free radicals attack the lipids in cell membranes.  Oxidative stress is not specific to ME/CFS but it does help us understand the biological processes that are going awry.

 

3. Scientists at RIKEN, Japan’s renowned research institution have shown that the ME/CFS brain is inflamed.  They used a particular kind of brain imaging to show that immune system cells in the brain were highly activated (inflammation) in people with ME/CFS, compared to healthy individuals.  They further showed that the greater the inflammation, the greater a person’s symptoms.  The inflammation was a chronic, continuing state.  Investigators from other countries including the U.S. are now collaborating with the Japanese team to develop possible diagnostic markers and effective treatments.

 

SMCI-Supported4. Central sensitization is state in which the pain-sensing mechanism in the central nervous system gets “stuck” in a highly reactive state.  When this happens, a simple bump or light pressure causes greater and more widespread pain than it otherwise would.  Central sensitization has been best demonstrated in people with fibromyalgia, an illness similar in many respects to ME/CFS.  New research on restrictions in range of motion in ME/CFS patients indicates that central sensitization may also explain the fatigue, brain fog and post-exertion malaise. 

 

SMCI-Supported5.  The immune system is built to attack “foreign” things (like germs) and substances (like plant pollen).  In autoimmune diseases, instead of attacking something foreign, the immune system attacks healthy cells and organs.  Since women experience higher rates of many autoimmune diseases, and since women appear to develop ME/CFS more often than men,  autoimmunity has been suspected as a possible cause of ME/CFS.  A clinical trial of rituximab, a drug that destroys B cells (these are the antibody producing cells of our immune system), showed benefit in a number of ME/CFS patients.   This result has suggested that autoimmunity may be present in at least a subset of ME/CFS patients.  There are also several studies that show elevated antibodies to various “self” proteins in ME/CFS patients.   Understanding the role of autoimmunity in ME/CFS will help identify biomarkers and target treatments.

 

6. Patient-centered outcomes research seeks to determine if a treatment is leading to an improved outcome: reduced symptoms and suffering.  One problem with outcomes research has been that the “outcomes” that doctors measure do not always reflect the outcomes that are important to patients.  For example, during a 2012 FDA patient-focused drug development teleconference, an ME/CFS patient told the audience that she knew she was doing better when she could stand in the kitchen and make a salad.  Another problem with outcomes research until recent years has been that it was very difficult for patients to report, and therefore for doctors to study, how well the patient was doing every day. Now web-based, smart phone or personal device tracking and monitoring technology is making it possible for patients to participate in patient-centered outcomes research from anywhere including the comfort of their home.

 

7. Risk factors are behaviors or conditions that raise the risk of developing a particular disease.  Identifying risk factors can help us understand how to control and prevent disease.  Smoking is a classic example of a factor that increases your risk of lung cancer. Epidemiological research has suggested a few risk factors for developing ME/CFS such as a history of viral infection. Research has shown that ME/CFS patients have a 2-fold increased instance of high allostatic load, a quantitative index of hormones, inflammatory and cardiovascular measures of the body’s physiological balance. It is not yet clear if the high allostatic load caused the ME/CFS or the ME/CFS caused the high allostatic load, but additional research may show that allostatic load can be used to screen patients to assess ME/CFS risk.

 

8. Abnormalities in the white matter of the brain (white matter contains the nerve bundles) have been found in ME/CFS patients using a variety of magnetic resonance imaging (MRI) scanning techniques. The abnormalities have been found throughout the brain (likely due to the heterogeneous nature of ME/CFS).  A team at Stanford University found that a specific area of white matter on the right side of the brain was altered, adding to the increasing evidence that the neurocircuitry is affected in ME/CFS patients.

 

SMCI-Supported9. Abnormalities of the autonomic nervous system have been found by numerous independent researchers. These include a failure of the body to maintain blood pressure after a person stands up, abnormal responses of the heart rate to standing and unusual pooling of blood in the veins of the legs. These heart rate abnormalities persist during sleep along with abnormal levels of hormones known to regulate the cardiovascular system.  This is further evidence of a physiological imbalance in ME/CFS patients.

 

10.  Although many viruses and other infectious agents are completely eliminated by the immune system after an infection, other viruses can remain “latent” in the body for a long time—even for the rest of a person’s life.  There’s evidence of more frequent latent active infection with various herpesviruses and enteroviruses. The herpesviruses include Epstein Barr, HHV-6 and cytomegalovirus. Other infectious agents, like bacterium that cause Lyme disease, Ross River virus and Q fever, can also trigger CFS.  Whether these chronic infections cause the symptoms of ME/CFS remains unclear.

__________

The road to real discovery and life-changing progress is long, arduous, costly. The Solve ME/CFS Initiative is taking strategic steps to shorten the road and speed up progress. Despite our modest budget, SMCI has made great strides and was the first organization to fund research into epidemiology, viral causes, immunology, neuroimaging, exercise physiology and the autonomic nervous system.

big-donate-modifiedAll of this research work is only possible because of the support of the many who fund it. The investments made by those suffering with ME/CFS and their loved ones have fueled the Solve ME/CFS Initiative’s work. With that support, we have become one of the largest and most successful private funders of ME/CFS research… paving the road to objective diagnosis, treatment and a cure.

 

Funding Research to Inform the Path Forward, part 2

December 10, 2014

The Solve ME/CFS Initiative (SMCI) began funding research into myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as soon as it was founded in 1987. But the first competitive funding opportunity occurred in 2008. In part 1 of this blog post we reviewed the advances made through this competitive funding cycle.

Read it HERERIWW.2

In this second part of the series, we share the progress being made through our second competitive funding opportunity, which occurred in 2011. That year, SMCI solicited research proposals that would bridge the gap between bench discoveries and clinical implementation by funding research aimed at discovery and replication of diagnostic and treatment biomarkers and exploring new drug targets and treatments for ME/CFS. Knowledge acquired would be used to attract pharmaceutical and biotech study as well as augment the evidence base for clinical practice and health policy. That year, we funded 5 investigators, bringing 2 additional new researchers into the field of ME/CFS. Through the virtual structure of the Research Institute Without Walls, every investigator now has a means to archive all of their results in a central place called RedCap – the Research Electronic Data Capture system.

This innovative, collaborative approach, along with Dr. Vernon’s knack for recruiting leaders into the field, has allowed SMCI to begin to change the paradigm while bringing important discoveries to light.

 

2011 Funded Investigators Progress Report
Six grants were awarded totaling $470,487 to investigators in the US and Canada.  To date this funding has led to more than $1.6 million in additional funding for our grantees.

The Solve ME/CFS Initiative awarded Biovista, a small biotech company, to find new uses for approved drugs – a process known as drug repurposing.  Spyros Deftereos, MD, PhD, vice president for drug discovery, was excited to research ME/CFS because of the neurological impairment and neurology-related mechanisms, an area Biovista specializes in. They used their proprietary software to explore the biomedical literature, pharmaceutical databases and the SolveCFS BioBank for all of the symptoms of ME/CFS then matched these with underlying mechanisms of these symptoms and drugs known to target these mechanisms. In less than a year, Biovista identified two drugs that, when used in combination, could potentially target fatigue and pain – two major ME/CFS symptoms. A proof of concept clinical trial needs to be conducted to determine the efficacy of this drug combination in ME/CFS. Biovista is currently seeking partners and raising funds to conduct this trial.

Dane B. Cook, PhD is associate professor of Kinesiology at University of Wisconsin, Madison.  SMCI provided funding to Cook to study the relationships between the post-exertion crash, gene expression and brain function in ME/CFS patients and controls. Post-exertion malaise (PEM) can be induced by physical and mental exertion and has been described by patients as a “crash” because of the relapse that occurs within 24 hours. This “crash” presents in a worsening of all symptoms affecting thinking and memory, heart function, and sleep for days or even weeks. Despite being a cardinal feature of ME/CFS, no single research group had ever evaluated the effects of mental and/or physical stress on PEM in a comprehensive manner. Cook’s team is using both an exercise challenge and mathematical mental challenge to define PEM. He has completed testing on most of the ME/CFS patients and all the healthy controls and is deep into analyzing this amazing dataset. He has teamed up with Alan Light and Gordon Broderick for an integrated, systems biology approach to defining PEM.  Because of the work he was able to do under our award, Cook recently received a $750,000 award from the Department of Veterans Affairs to conduct the same study in Gulf War Veterans. (Go to https://www.youtube.com/watch?v=k7OLt6J4ySk&feature=youtu.be to watch Dane Cook’s webinar in which he presents his research results.)

Patrick O. McGowan, PhD, is an assistant professor of neuroscience and epigenetics at the University of Toronto. McGowan’s award allowed him and his team to study epigenetics – a first of its kind study for ME/CFS. Epigenetics refers to patterns of change in gene expression—not the gene itself—that occur in response to such things as nutrition, infection and physical and mental trauma, not genetic factors. These outside influences trigger a process called methylation that affects gene function but doesn’t change the underlying DNA structure. McGowan and his team used the SolveCFS BioBank for this innovative study; they’ve already published results in PLOS One, an open-access high-impact journal and are preparing the next set of results for publication. SMCI has provided McGowan with additional funding because his research shows promise for delineating ME/CFS subtypes and identifying biomarkers. Further, because of the results achieved through our seed funding, McGowan has received $845,000 from the Department of Defense to establish an animal model to further study how these epigenetic changes effect the immune and endocrine response. (Go to https://www.youtube.com/watch?v=QjrBP7MFVPY&feature=youtu.be  to watch Patrick McGowan’s webinar in which he presents his research results.)

Peter C. Rowe, MD is the Sunshine Natural Wellbeing Foundation Professor of Chronic Fatigue and Related Disorders at Johns Hopkins University School of Medicine. Rowe was the first to describe the connection between orthostatic intolerance and ME/CFS. The Solve ME/CFS Initiative has funded Rowe to determine if neuromuscular strain increases the cardinal symptoms, contributes to post-exertional malaise and increases central sensitization. Central sensitization is the process of the brain and nervous system becoming more sensitive and reactive. In Fibromyalgia for example, central sensitization helps explain why light pressure is felt as intense and widespread pain. So far Rowe’s research indicates that ME/CFS patients have more body areas with impaired range of motion and are more likely to have abnormal responses like increased heart rate variability to simple physical examination maneuvers. He’s published these results and is now analyzing how central sensitization might help explain post-exertion malaise.  (Go to http://www.youtube.com/watch?v=YnCcEoFSgvc&feature=youtu.be to watch Peter Rowe’s webinar in which he presents his research results.)

 

In part one of this series we discussed the 2008 funding cycle and the progress being made through those researchers. Read it HERE

On December 16th we will be holding a free webinar where we distill this information a bit more and answer your questions about this research progress and what it means to you. Register for that webinar today HERE.

https://attendee.gotowebinar.com/register/119787780;jsessionid=abc276q-OYylr4Ky6axOu

 

The road to real discovery and life-changing progress is a long, arduous and costly. The Solve ME/CFS Initiative is taking strategic steps to shorten the road and speed up progress. Despite our modest budget, SMCI has made great strides and was the first organization to fund research into epidemiology, viral causes, immunology, neuroimaging, exercise physiology and the autonomic nervous system.

big-donate-modifiedAll of this research work is only possible because of the support of the many who fund it. The investments made by those suffering with ME/CFS and their loved ones have fueled the Solve ME/CFS Initiative’s work. With that support, we have become one of the largest and most successful private funders of ME/CFS research… paving the road to objective diagnosis, treatment and a cure.

Funding Research to Inform the Path Forward, part 1

December 9, 2014

The Solve ME/CFS Initiative (SMCI) began funding research into myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as soon as it was founded in 1987. But the first competitive funding opportunity occurred in 2008. That funding cycle solicited research proposals that would advance the discovery of biomarkers and methods for early detection, objective diagnosis and effective treatment of ME/CFS, and included a rigorous review process. That year, SMCI awarded 6 grants, engaging 3 researchers who were new to the field of ME/CFS research. All agreed to use similar measures, share data and collaborate with one another – breaking down the silos researchers typically work in.

RIWW.2In 2010, SMCI launched our Research Institute Without Walls, offering a stronger ‘virtual’ infrastructure to support collaboration and data-capture. This was also the year SMCI launched the SolveCFS BioBank™ – an important resource for researchers, lowering barriers, reducing costs and attracting new investigators into the field.

2011 brought our second competitive funding opportunity. SMCI solicited research proposals that would bridge the gap between bench discoveries and clinical implementation by funding research aimed at discovery and replication of diagnostic and treatment biomarkers and exploring new drug targets and treatments for ME/CFS. Knowledge acquired would be used to attract pharmaceutical and biotech study as well as augment the evidence base for clinical practice and health policy. That year, we funded 5 investigators, bringing 2 additional new researchers into the field of ME/CFS. Through the virtual structure of the Research Institute Without Walls, every investigator now has a means to archive all of their results in a central place called RedCap – the Research Electronic Data Capture system.

This innovative, collaborative approach, along with Dr Vernon’s knack for recruiting leaders into the field, has allowed SMCI to begin to change the paradigm while bringing important discoveries to light. In this two part blog series we explore our funded research projects in more depth.

 

2008 Funded Investigators Progress Report

Six awards totaling $647,940 were made to investigators in the US and Canada.  Our 2008 grant funding led to more than $7 million in follow-on funding from federal agencies for several of the investigators listed below. In other words, we provided important seed money.

Eric Aslakson, MS and Bud Mishra PhD, Professor of Computer Science & Mathematics New York University are accustomed to dealing with massive amounts of data.  Their 2008 award was to create a relational database of the 20 million abstracts in PubMed to begin to translate publicly available biomedical knowledge to further our understanding of ME/CFS. The Solve ME/CFS Initiative is now contracting with Eric’s company, Poiema, LLC, to utilize large scale natural language processing techniques to analyze hundreds of thousands of ME/CFS-related full text journal articles and all 20 million PubMed abstracts to categorize and explore biological relationships detailed in text and open source biological datasets.  When complete, the system will allow querying of complex biological causal relationships to elucidate ME/CFS etiology and potential treatment methods.

Gordon Broderick PhD, professor at NOVA Southeastern University and Ben Katz, MD professor of pediatrics at Northwestern University Feinberg School of Medicine teamed up to identify predictive markers of post-infection fatigue. Their 2008 award from the Solve ME/CFS Initiative was used to study samples that Katz had collected from an NIH-funded study. Broderick applied his computational skills to create a model of how the molecules worked and communicated with each other. (He spent years as a chemical engineer before Dr. Vernon recruited him into the field of ME/CFS research.) The Broderick team showed that five specific cytokines might be useful in diagnosing ME/CFS that occurs as a result of infection. Our 2008 award to Broderick has helped him receive funding from the Department of Defense to extend these findings in both ME/CFS and Gulf War Illness. He is also co-investigator on grants made by the National Institutes of Health to Mary Ann Fletcher and Nancy Klimas.

Alan R. Light PhD and Kathleen C. Light PhD are both research professors at the University of Utah.  The Light team generated intriguing preliminary data of receptors on blood cells that detect metabolites that could be biomarkers for fatigue and pain. SMCI awarded the Lights a grant to increase the sample size and test the markers in other diseases. Subjects in their study provided blood samples before and several times after riding a stationary bicycle to induce fatigue and the post-exertion crash. The Lights confirmed that the metabolite detection sensory gene expression increased following exercise in ME/CFS patients but not in the other disease groups or in healthy controls. They have received more than $2 million from the National Institutes of Health to learn more about these sensory receptors and how they can be used as biomarkers for ME/CFS. Even more important, the Light team continues to collaborate with our funded investigator Dane Cook to examine these biomarkers in Cook’s study.

Marvin Medow PhD, Associate Director of the Center for Hypotension at NY Medical College and Julian Stewart MD, PhD, Director of the Center for Hypotension at NY Medical College received an award from SMCI in 2008 to investigate how blood flow and orthostatic intolerance affect the flow of blood to the brain in ME/CFS patients. Medow and his team have been one of the most prolific scientific teams we’ve funded, publishing more than 10 papers in the biomedical literature. These results describe altered blood flow to the brain and how this altered flow affects ME/CFS symptoms, particularly brain fog. SMCI funded Medow again in 2011 to study how various treatments could be used to increase the blood flow to the brain. The Medow team has just published a paper showing that phenylephrine (a drug that increases blood pressure) improved blood flow to the brain when ME/CFS patients were on a tilt table and this improved blood flow correlated with improved cognitive testing.

Dikoma Shungu PhD, Professor of Physics in Radiology at Weill Cornell Medical College and Sanjay Mathew MD now Associate Professor of Psychiatry at Baylor College of Medicine were awarded seed funding by SMCI to use a powerful imaging technology known as proton magnetic resonance spectroscopic imaging to measure brain metabolism and oxidative stress in ME/CFS compared to other diseases and healthy controls. They published several papers and showed conclusively that there was oxidative stress (increased levels of reactive oxygen species) in the brain of ME/CFS patients. Shungu and his team went on to receive more than $1.4 million from the National Institutes of Health to continue studying the role of oxidative stress in ME/CFS and how it may be treated.

Sanjay Shukla PhD and Steve Yale MD of Marshfield Medical Research Foundation in Marshfield Wisconsin received a grant from SMCI to determine whether the gut microbiome was affecting post-exertion relapse. Shukla and Yale teamed up with Dane Cook at University of Wisconsin to conduct the exercise challenge testing and the Light team in Utah to test the blood biomarkers (described above). ME/CFS patients and controls provided blood and stool samples before and after the exercise challenge and reported their symptoms before and after the exercise challenge to determine the extent of their post-exertion relapse. The Shukla team identified another gene that was expressed in ME/CFS patients that correlated with their post-exertion symptoms. They also found increased microbe DNA in the blood (that likely came from the gut microbes) in both patients and healthy people following exercise. These results are being prepared for publication and put an interesting new twist on possible causes of the cardinal feature of ME/CFS – post-exertion crash.

In part two of this series – coming soon – we will discuss the 2011 funding cycle and the progress being made through those researchers.

On December 16th we will be holding a free webinar where we distill this information a bit more and answer your questions about this research progress and what it means to you. Register for that webinar today HERE.

https://attendee.gotowebinar.com/register/119787780;jsessionid=abc276q-OYylr4Ky6axOu

For the many of our readers who have donated to our organization, you can take pride in having supported this important work to advance ME/CFS understanding.

Being “Patient-Centric”

December 8, 2014

SMCI_MarkAs our logo depicts, patients are central to a solution for ME/CFS.  We have designed our SolveCFS BioBank™ to collect and manage data so that the individual is the central organizing principle. A patient-centric design allows for patterns to emerge from the group of biobank participants, while capturing unique individual information. In the future, our SolveCFS BioBank™ will collect experiential, health and genomic information as well as health history and genetic profiles from a large number of individuals, allowing us to identify disease determinants.

The patient-centric design of our SolveCFS BioBank™ allows individuals to participate in many different types of research studies – through online surveys and by providing a genetic sample (i.e. blood) – all without ever leaving their homes.  A single carefully collected and processed blood sample can be used to detect antibodies, quantify cytokines, measure gene expression, sequence genes, and examine chemical modification, measure metabolites and more.  Importantly, all of the data generated on each individual stays connected to that individual through their assigned global unique identifier (GUID), creating a biological explanation specific to the individual while maintaining the individual’s anonymity and privacy.

BioBank_PatientCentric

The SolveCFS BioBank™ was the first to use a patient-centric design specifically for ME/CFS. Here are some of the researchers that are generating patient-centric data on samples currently in the SolveCFS BioBank™ inventory to help Solve ME/CFS:

  • Michael Cooperstock, M.D., MPH, University of Missouri Health System
    Cooperstock partnered with Madeleine Cunningham, PhD and David Kem, MD of the University of Oklahoma and Armin Alaedini, PhD of Columbia University to test blood samples for autoantibodies to a number of different human proteins.  Alaedini has made a finding that may help describe an ME/CFS subtype. Results are being prepared for publication.
  • Stephen J. Elledge, PhD, Howard Hughes Medical Institute, Harvard University
    Elledge developed a technology that reveals all the viruses targeted by the antibodies in the blood, detecting the interactions between antibodies and the millions of virus proteins, thereby generating millions of data points for each sample. Elledge and his team have completed the testing and are now analyzing the data to determine whether antibodies against viruses are different in ME/CFS patients compared to other diseases and against healthy controls.  We will report on these important findings in 2015.
  • Michael Houghton, PhD, Lasker Laureate, Canada Excellence Research Chair in Virology, Professor in the Department of Medical Microbiology & Immunology, University of Alberta
    Houghton is using samples to validate a possible diagnostic biomarker he has identified for ME/CFS.  Analysis of this potential biomarker validation is underway and we hope to describe it in 2015.
  • Leonard Jason, PhD, Professor, Center for Community Research, DePaul University
    Jason focuses his research on case definition for ME/CFS.  For the past 2 years he has used the clinical information in the SolveCFS BioBank to understand how best to classify and define ME/CFS patients.  So far Jason and his team have published 2 papers and another is under consideration describing their work using the SolveCFS BioBank™ data.
  • Derya Unutmaz, MD, Professor of Microbiology and Pathology, NYU Medical Center
    His laboratory has developed highly sophisticated and detailed profiling technology of the functional subsets of immune cells isolated from human blood.  Unutmaz has completed immune profiling on 25 ME/CFS patient samples from the SolveCFS BioBank™ and is now in the process of analyzing the data, comparing it to immune profiles from other diseases as well as from healthy controls.  (Please go to https://www.youtube.com/watch?v=c9ikUVCXnhU&feature=youtu.be to watch a recent webinar led by Unutmaz on his work.)

Our intention is to evolve the SolveCFS BioBank™ into the most sought after resource for ME/CFS research in existence. In order to achieve this, we must grow in a rigorous and strategic manner.  If you are already signed up, you are our research-ready momentum leaders. Your registration already makes you part of the solution. If you haven’t yet signed up, please contact Gloria Smith at BioBank@SolveCFS.org or by phone at 704-362-2343 to learn more.

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The Solve ME/CFS Initiative is targeting our work in order to one day understand ME/CFS at an unprecedented molecular level and be able to guide research and development of new diagnostic tests and better treatments. Your support and participation has gotten us this far and it is critical to the path forward. Please consider a gift that is meaningful to you – any and every donation help fuel the path forward.

Restructuring Medical Research

December 5, 2014

questionAt the Solve ME/CFS Initiative, we are often asked “why is it taking so long for research to come up with something that is going to help me?”

According to a recent article in MedicineNet.com, in the US, it takes an average of 12 years for an experimental drug to travel from the laboratory to your medicine cabinet. Only 5 in 5,000 drugs that enter preclinical testing progress to human trials. And only 1 of these 5 drugs that are tested in people is approved. The chance for a new drug to actually make it to market is only 1 in 5,000.

Though it has been 20 years since the Fukuda case definition for ME/CFS was created and 11 years since the more popular Canadian Consensus Criteria was developed, diagnosis still takes far too long and treatment options for people with ME/CFS have not improved much. So how can the status quo be changed?

broken_systemFirst, we have to understand why the current system for medical research doesn’t work for patients.

  • Individual scientists decide what they want to study based on their skills and training, not what is the most urgent need of patients.
  • Scientists and doctors are not incentivized to cooperate and work together to understand diseases and find treatments and cures more rapidly. Instead, they compete for limited resources and funding, a process that pits them against one another. In the struggle for competitive advantage they often protect new ideas and their scarce resources; access to patients, data and bio samples because being the first to publish a new discovery is vital for career promotion and future funding.
  • Rigorous peer review originally designed to ensure only the best science funding can result in scientific incrementalism – i.e. Reviewers want to ensure competitors don’t get too far ahead of the herd, making the peer reviewer’s future proposals less attractive. Historically, government funding mechanisms have rewarded this behavior in the name of scientific excellence.
  • Most research is hypothesis-driven, meaning that the experiments are designed to prove or dis-prove a specific theory. This hypothesis-driven approach rewards scientists for studies that are very narrowly focused, typically only looking at one or two experimental variables, which can be measured in laboratory animals or a small group of carefully selected patients, under closely controlled conditions.
    • These research design conditions generally do not replicate the human disease or the general patient population. Access to research data is limited to what appears in the publication and supports their hypothesis.
  • Even the most important studies frequently suffer from too few animals or people being tested to ensure the results are reliable, reproducible and broadly applicable.
  • Scientific journals will not publish negative results so the same failed experiment may be conducted repeatedly by different labs.
  • Human studies are limited by regulatory requirements, difficulty in finding enough patients and the time required to recruit them.  All this adds substantial, often prohibitive, cost.
  • There is virtually no funding to repeat even the most important experiments. Subsequently it is now estimated that up to 90% of the experimental results published in scientific and medical journals cannot be reproduced. Experiments that cannot be repeated, and results that cannot be replicated, have limited value for patients.

Solve ME/CFS Initiative is working to change these fundamental, unproductive structural problems in our work. Through the SolveCFS Biobank™, we ask patient and controls to contribute their health data and biosamples for research studies. Our goal is to bring together enough patients to be representative of the entire ME/CFS community. We are catalyzing research by providing access to patient samples and data for any qualified researcher who wants to help us solve ME/CFS better, faster and cheaper.

Through our funding program, SMCI supports researchers who want to test patient samples to understand what ME/CFS is and how it works at a molecular level (e.g. how genes or microorganisms in the gut contribute to ME/CFS or how ME/CFS changes metabolism by measuring proteins, lipids or hormones in the blood). We can and have supported studies to replicate research findings that help define ME/CFS and confirm that the findings are accurate and reproducible. And our Research Institute Without Walls creates a collaborative environment where one researchers efforts can be informed by and learn from another. Collaborations are being built and innovative approaches are coming to fruition.

In the future, with additional funds, we can expand this work and do more. We envision a day when we will build a platform for collecting, storing and sharing data from the ME/CFS community and ALL ME/CFS research (including research not funded by our organization) so that the best minds in computer science and bioinformatics, using the most advanced software, can add to our definition of ME/CFS and its sub-types. Today, no comprehensive ME/CFS research database exists. We envision testing these definitions in the lab and in clinic, demonstrating to diagnostic and pharmaceutical companies that we have the data they need to invest in developing new diagnostic tests and treatments for ME/CFS. It is the for-profit diagnostic and pharmaceutical companies that have the very substantial R&D resources to run the final lap toward approved FDA drugs for ME/CFS.

Our work is to fund and organize rigorous, expansive, early research to deliver results that lead to the development of new diagnostics, therapies and cures as quickly as possible. This is not an easy task. Even with a team of the best scientists and clinicians, using the best available technology it will take years. But the millions of people suffering from ME/CFS know we cannot afford to wait!

The Solve ME/CFS Initiative is targeting our work in order to one day understand ME/CFS at an unprecedented molecular level and be able to guide research and development of new diagnostic tests and better treatments. Your support and participation has gotten us this far and it is critical to the path forward.

 

big-donate-modifiedAs we approach year end, many are considering giving to a charity that is close to their heart. You have the power to ensure the good work of our organization continues to propel us all closer to a day when the world is free from ME/CFS. Any and every gift makes a very real difference in this fight to make ME/CFS understood, diagnosable and treatable.

Together we will solve ME/CFS.

Gift Registry for a Cure

December 3, 2014

An inspiring way to support the Solve ME/CFS Initiative (SMCI)

AaronPaas_download

Aaron & his sister, Danielle

When the sister of our board member Aaron Paas, Danielle, became ill with ME/CFS six years ago, like so many patients she went from vibrant and busy to severely ill and debilitated almost overnight.  “It left me completely bed-ridden for the first few months,” said Danielle.  “I could barely even lift a bite of food to my own mouth.”

It took Aaron a couple of years to really zero in on what was going on with Danielle. In his search for information and answers he stumbled on Solve ME/CFS Initiative (then the CFIDS Association of America) and became interested in the work the organization was doing to improve the lives of people with ME/CFS. “I love the focus that SMCI puts on funding the research that will solve ME/CFS” Aaron said.

So when Aaron and his fiancé, Haley, were setting up a registry for their wedding, the Boston couple wanted to find a powerful way to get people to understand a little bit about what Danielle’s life is really like. “She’s such a positive person that most people have no idea what she’s actually going through,” explained Aaron. “I was confident that by making the disease real, people would be compelled to do something about it.”

Excited by the concept, when the couple set up their wedding website, on the registry page they included a link to Danielle’s painful ME/CFS story and extended an invitation for guests to give the gift of hope by donating to SMCI.

“There is no cure for ME/CFS and no treatment available within the medical system, a fact that can make the future seem bleak at times,” Danielle wrote to her brother’s wedding guests. “However, I am able to have hope for my future because of the knowledge that the people at Solve ME/CFS Initiative are working tirelessly to solve ME/CFS.  Because of SMCI, I have hope that there will one day be a cure for ME/CFS.”

Aaron and Haley

Aaron and Haley

As their Aug. 2 nuptials approached, Aaron and Haley were elated to be tying the knot. “It’s so exciting to think that the work that SMCI is doing right now through the funding we’re helping raise could unlock the key to giving Danielle back the physical strength to match the strength of her spirit.”

And their excitement was bolstered by a far-reaching outpouring of support. “One of the cool parts of putting it on our wedding registry site was that it was right around international awareness day in May, so a few of us asked people on our social networks to share the story,” explained Aaron. “It travelled a lot more than we expected and we got over 5,000 people that week to visit the site and read the story, a ton of whom wrote back to Danielle telling her that it was the first time they really understood the power of ME/CFS, even some friends she’s known for 20 years.”

Aaron and Haley’s powerful network of support for Danielle through the SMCI is encouraging both to the Paas family and to our organization. With this kind of support, we really are one step closer to a world without ME/CFS.

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As the holidays approach, perhaps you are looking for a creative way to support the work of the Solve ME/CFS Initiative?

Crowdrise.com allows you to quickly and easily set up a personal web page then raise money for a cause you care about – ME/CFS Research through the Solve ME/CFS Initiative! – by inviting your family and friends to make donations.  Some of our supporters have asked their family and friends to give to their Crowdrise campaign for the Solve ME/CFS Initiative this year instead of gifts.  Others are simply asking family and friends to give in the holiday spirit.  Once you’ve created your page, you can get the message out via email, Facebook, Twitter, or any other tool you choose. Check out our profile on Crowdrise at www.Crowdrise.com/SolveCFS

If you are considering including SCMI in your own registry, have an idea for a personal fundraising campaign, or want to join our 10/$12 Challenge, please contact Erin E. Parsons-Wright, Director of Development, at eeparsonswright@solvecfs.org or call 704-364-0016.

The Solve ME/CFS Initiative (SMCI) funds its cutting-edge research program entirely through the generous gifts of individuals—ME/CFS patients and those who care about them.  These contributions fund research that is making real progress through our Research Institute Without Walls and SolveCFS Biobank™.  Please give and keep this vital progress moving forward.

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Together, we’re achieving our mission to make ME/CFS widely understood, diagnosable and treatable.

Giving Tuesday 2014 – Join the 10/$12 Challenge!

December 2, 2014

You can fuel progress for ME/CFS research this Giving Tuesday and Beyond!

We gave thanks on Thanksgiving,  got great shopping deals on Black Friday and Cyber Monday, and now it is Giving Tuesday, a global day for giving thanks and giving back. It’s not about saving money but changing lives and anyone can play a part.

It starts today but can continue well through year-end.  You can make a difference:

 1. Join our 10-$12 Challenge on Crowdrise!

10_12ChallengeThe Challenge: be one of 1,000 people willing to recruit 10 friends to donate $12 each

The Goal: $120,000 Raised between Giving Tuesday, 12/2, and the end of the year, 12/31/2014.

The Reason: Exciting progress is being made. The Solve ME/CFS Initiative is gaining momentum toward our goal of a world free of ME/CFS. We simply must fuel more research and increase our momentum toward making ME/CFS understood, diagnosable and treatable.

It is easy and EVERYONE can help! Here’s how your investment can make a difference just $12 at a time:

  • $12 (1 friend donates $12) allows us to process one person’s initial consent paperwork to begin the enrollment process into the SolveCFS BioBank
  • $60 (5 friends donate $12 each) can cover the costs of processing one biological sample into the BioBank, which will ultimately place the most valuable resource in a researchers hand – the patient.
  • $96 (8 friends donate $12 each) is equivalent to processing fees for one registrant into the Biobank, including assigning the important GUID (global unique identifier) that allows us to consolidate information on the sample across a variety of studies.
  • $264 (22 friends donate $12 each) allows us to offer one free online webinar, educating and empowering patients across the US and across the globe with investigator updates and cutting edge research progress.
  • $600 (50 friends donate $12 each) allows us to deliver the free monthly e-newsletter, Research1st for 10 months – bringing important research highlights, federal news updates, disease management information and more right to thousands of patients and loved ones completely free of charge
  • $1,200 (100 friends donate $12 each) is equal to funding one week of research by one of our funded investigators… Research that could lead to biomarker validation, a solid case definition, validating patient-reported outcomes, and unlocking secrets to autoimmunity, viral pathogens, epigenetics, and immune function in ME/CFS

 

Crowdrise.com allows you to quickly and easily set up a personal web page then raise money for a cause you care about – ME/CFS Research through the Solve ME/CFS Initiative! – by inviting your family and friends to make donations.  Some of our supporters have asked their family and friends to give to their Crowdrise campaign for the Solve ME/CFS Initiative this year instead of gifts.  Others are simply asking family and friends to give in the holiday spirit.  Once you’re created your page, you can get the message out via email, Facebook, Twitter, or any other tool you choose.

Here’s how to do it:

  1.  Visit https://www.crowdrise.com/SMCI1012Challenge
  2. Click on “ Set up your fundraiser,” and then select the “start your own fundraiser” option
  3. Follow the instructions, filling in all of the fields to set up your campaign – you can upload a picture, tell your own story and create a simple URL to share
  4. Email your family and friends, sharing the link/URL you created when you signed up. By following that link they can easily donate to your campaign! It’s that simple.

Need help?  Email Erin Parsons-Wright, Director of Development, at eeparsonswright@solvecfs.org or call 704-364-0016

 

2. Donate!

big-donate-modifiedThe Solve ME/CFS Initiative (SMCI) funds its cutting-edge research program entirely through the generous gifts of individuals—ME/CFS patients and those who care about them.  These contributions fund research that is making real progress through our Research Institute Without Walls and SolveCFS Biobank™.  Please make a donation in honor of Giving Tuesday and keep this vital progress moving forward.

Together, we’re achieving our mission of working to make ME/CFS widely understood, diagnosable and treatable.

Deciphering Post-Exertional Malaise

November 21, 2014

Guest Blog by Dane B. Cook, PhD

On September 18, 2014, Dane B. Cook, Ph.D., Associate Professor of Kinesiology at the University of Wisconsin, Madison and a Solve ME/CFS Initiative 2011 funded investigator, presented a webinar on the system biology approach his team is taking to provide a clear picture as to what causes post-exertional malaise. You can access the full recording of the webinar HERE.

In this guest post for our blog, Dr. Cook reviews the material presented and tackles the many questions we received from webinar participants.

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Post-exertional malaise (PEM) has been called “the illness within the illness” (Anthony Komaroff, 2011). It is the defining and cardinal symptom of myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and yet the term used to describe it is a horrible one that does not do justice to the suffering that patients experience. Deciphering PEM is a critically important area of research for ME/CFS; you can’t begin to fix a problem like post-exertional malaise until you can understand its underlying cause. The goal of our research is to help our understanding of PEM so that we are able to mitigate its effects.

In the webinar I discussed both the clinical and laboratory characteristics of Post-Exertion Malaise (PEM) emphasizing that the patient experience and the laboratory study of PEM do not always coincide well with one another.

Clinical Perspective
There are several ‘descriptions’ or case definitions currently in circulation for ME/CFS. The international consensus criteria (Carruthers et al., 2011) offers a detailed clinical description of PEM and has potential utility for physicians. This case definition refers to PEM as Post-exertional neuroimmune exhaustion (PENE) and notes that it is a required symptom for the disease. It describes PEM or PENE as:

  1. Marked, rapid physical and ⁄ or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
  2. Post-exertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
  3. Post-exertional exhaustion may occur immediately after activity or be delayed by hours or days.
  4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.
  5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

The current clinical description of PEM makes note of the large variability in time-course, severity and symptom make-up of this phenomenon among patients. This highlights the very real need for more research on these topics.

Research Perspective
Current clinical descriptions and case definition criteria of PEM are not currently quantified well-enough to be used in the laboratory setting. As a result, most studies have had to operationally define PEM. This has led to PEM being described and defined in a host of different ways including:

  • Increased symptoms of pain & fatigue
  • Reduced physical activity levels
  • Abnormal exercise responses
  • Changes in cognitive function
  • Circadian rhythm/period changes
  • Sleep disruption
  • Impaired pain regulation (central nervous system sensitivity)
  • Various biological markers (e.g. complement C4a, cytokines, natural killer cells, NF-кB, oxidative stress, gene expression, etc.)

Too many studies that have defined PEM based on biological outcomes have failed to measure symptoms. This is problematic because unless you demonstrate that biology is related to illness severity, you cannot attribute any changes in biology to the phenomenon of interest (in this case PEM).

The Solve ME/CFS Initiative funded a study led by my Master’s student Jacob Meyer.  This study, published in 2013 in the journal Fatigue: Biomedicine, Health & Behavior, is an example of how we study PEM in the lab.

  • This study examined gene expression for metabolite, immune and sensory receptors and symptoms pre and post exercise in ME/CFS patients and healthy controls who were matched on age and fitness. The study was an extension and replication of the work of Light and colleagues (2009; 2011) at the University of Utah.
  • Results showed that maximal exercise resulted in sustained up-regulation of the glucocorticoid (NR3C1) and alpha 2A adrenergic receptors for up to 72 hours in ME/CFS patients compared to controls.  Importantly, these changes in gene expression were significantly related to symptoms of pain, fatigue and confusion. These results demonstrate that ME/CFS patients have a different physiological response to exercise, one that appears to be consistent with exercise inducing an inflammatory state in ME/CFS patients and that clearly has negative consequences.

Our most recent study, “Post-exertion malaise in CFS/ME: Brain, inflammation and behavioral interactions”, also funded by SMCI, is a collaborative effort with Alan and Kathy Light at the University of Utah and Dr. Gordon Broderick at Nova Southeastern University in Florida. The project is a direct extension of our previous work (Meyer et al., 2013) and adds two critical components. The first is assessment of brain responses to cognitive tasks during a state of PEM. The second is the use of a “systems biology” approach to data analysis.

  • The overall goal of this study is to determine the dynamic relationships between brain structure and function, gene expression for sensory, adrenergic and immune receptors and self-reported symptoms in CFS/ME using a model of PEM
  • The key concept is that determining the interaction between several physiological systems (i.e. central and peripheral systems) will better predict PEM than determining the influence of any single system independently

The study protocol:

  • On Day one, we screen all participants for either ME/CFS or as healthy
  • Day two consists of detailed symptom measurement and functional brain imaging of both fatiguing and non-fatiguing tasks. Blood is collected both prior to and following brain imaging.
  • One week later participants return for exercise testing. A blood sample is taken and symptoms are measured. Participants exercise at 70% of peak heart rate for 30 minutes. Metabolic, heart rate and lactate responses to exercise are measured. Blood and symptoms are measured during the first 15 minutes post exercise.
  • Participants return 24-hours later for their second functional brain imaging session (i.e. they repeat day two of testing)

Cook_StudyProtocol

Though this study is not yet completed, this is what our preliminary data is showing:

  • Variability in symptoms from pre- to 24 hours post-exercise. These data demonstrate an incredible amount of variability in the magnitude, number and types of symptoms reported by patients. The variability is likely the result of a number of reasons such the severity of symptoms at baseline (i.e. ceiling effects), the individual time course of PEM (i.e. it may not have peaked for certain individuals) and how sick the patient was at study entry.

Cook_VariableSymptoms

  • Cognitive performance and brain responses for the fatiguing cognitive task. Patients tended to perform worse as they became more fatigued and performed more poorly post- compared to pre-exercise. The opposite was observed for controls. They tended to show improved performance during the first day and continued to improve 24 hours post-exercise.
  • Brain responses during the cognitive task reflected the cognitive performance results. ME/CFs patients showed greater brain activity than controls at baseline in brain regions involved in executive control (i.e. anterior cingulate and inferior frontal cortices) and memory (bilateral hippocampus).

Cook_BrainResponse1

Cook_BrainResponse2

Importantly, ME/CFS patients showed a different change in brain responses 24-hours post-exercise than controls and these changes in brain responses were significantly related to changes in symptoms. These data show that acute exercise has neural consequences for patients, suggesting that central nervous system outcomes are predictive of PEM.

Cook_BrainActivity1Cook_BrainActivity2

My take home messages:

  • Post-exertion malaise affects both the immune system and the brain.
  • No single outcome or biochemical is likely to explain the complexity of PEM
  • Determining physiological systems interaction will be critical towards understanding the mechanisms of PEM and perhaps how ME/CFS symptoms are maintained and/or exacerbated
  • There is still a large gap in our knowledge of what PEM is in terms of time course, variability, severity and primary symptoms.

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This was our highest attended webinar of the year and there were far more questions submitted than we were able to cover during the webinar. Dr. Cook graciously took the time to answer a majority of the individual questions submitted and those responses are below.

Webinar Q & A

Q: Are there ME/CFS exercise studies with brain imaging before, during & after exertion?

A: To our knowledge only the study by Rayhan et al., (2013)in Gulf War Veterans with ME/CFS has looked at brain responses pre and post exertion.

 

Q: Why do you say “subjective” response & not “objective” to maximal exercise?

A: The subjective response I was referring to was the symptoms that the patients experience post exercise. We also focus on the objective responses to the exercise such as oxygen consumption.

 

Q: Are you taking in to consideration the age of your patients and the length of time ill when you look at your results?

A: We will look at this preliminarily, but with a sample size of 15 it may be tough to demonstrate a statistical effect. This is something we are certainly interested in and hope to be able to investigate in a larger study.

 

Q: Do you have a list of examples that you can offer about PEM to help physicians and others better understand that this is a disease within a disease?
A: Some personal examples:

  • Need to stop grocery shopping mid-shop, stow shopping cart, lay-down in car for ½ hour and then return to finish shopping
  • Completely unable to perform activities of daily living
  • A debilitating crash following minimal exertion that can take weeks to recover from

A: Here is the 2011 case definition PEM list:

  • International Consensus Criteria (Carruthers et al., 2011)

A. Post-exertional neuroimmune exhaustion (PENE): Compulsory

1. Marked, rapid physical and ⁄ or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.

2. Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.

3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.

4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.

5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

Q: Have they found any muscle shut-down and/or myclonis with PEM?

A: Not to my knowledge

 

Q: Are you using functional MRI’s versus regular ones?

A: we are using both MRI (to look at brain structure) and fMRI (to look at brain function.

 

Q: Are you working with anyone in the Northwest (Portland)?

A: We are not currently working with Northwest US researchers.

 

Q: Can you tell us more about the effects seen with the HPA axis, particularly (eventually) effecting hormones: neuro, reproductive, thyroid?

A: It is too early to tell the cause or consequence of our glucocorticoid findings. Although the HPA-axis is an attractive hypothesis, the receptor response we are seeing could also be in response to inflammation. Some of the downstream consequences, if are results are confirmed, could mean that the neuroendocrine system is being affected in ME/CFS. This system regulates a host of hormones, the immune system, mood, storage and spending of energy. This system also interacts with numerous brain structures that interact with these systems.

 

Q: Can the different results of the symptoms be because there are not enough patients in the study?

A: This could certainly be a factor for average changes in symptoms for the group, however the individual variability we are seeing is not due to small samples. It’s showing us that PEM is highly variable and that we need large samples to study this variability in depth.

 

Q: Is IL2 refering to Interleukin 2?

A: Yes

 

Q: Is the PASAT the same version as for diagnosing MS?

A: I’m not sure if it is the same as used in MS research, but if not, it is very similar.

 

Q: Did this study include ME/CFS with fms??

A: We did not exclude for FM and yes some of our participants have both. We will look closely at this during our final analyses.

 

Q: Do repetitive episodes of PEM decrease a patients chance to recover from CFS/me?

A: I do not know the answer to this question, but it is a good one.

 

Q: Do these PEM abnormality show equally to M.E. AND Fibromyalgia patients?

A: This question is unknown (no data that I’m aware of) and it’s also a very good question.

 

Q: Do you think changes in brain scan images are a sign that there is brain damage or just a side effect of the illness?

A: The scans I presented do not tell us whether there is overt brain damage or not. They inform us if the structure of the brain is different in size and whether brain function differs during a particular task between patients and controls and in our case pre and post exercise.

 

Q: Is their lactic acid build up in muscles with exercise?

A: Yes, particularly for exercise that is of higher intensity.

 

Q: Does the up-regulation in in NR3C1 mean that cortisol level are extremely low or non-existent in the morning when cortisol levels are supposed to be the highest?  And non-existent levels throughout the day known as adrenal fatigue?

A: The up-regulation we see could be in response to low levels initially or it could be in response to regular levels that don’t necessarily function optimally. Our data suggest that baseline levels of expression are not different between patients and controls, but this does not mean that the actual receptor numbers do not differ. That requires a different blood analysis.

 

Q: Were levels tested before exercise?

A: Yes, we tested levels at baseline. For our first study blood level for gene expression did not differ between patients and controls. I will add though that brain responses to cognitive tasks have differed at baseline.

 

Q: Have they studied Chronic Pain Patients in these same ways?

A: There are post-exertion malaise studies in chronic pain patients, but these tend to not have blood or brain outcomes. They tend to measure pain responses to pain stimuli.

 

Q: Is it possible to do research on patients that cannot function at a level to exercise for 30 minutes or do a 2 hour mental task? That IS the reality for so many of us. Even if you live in the area, just getting to the hospital for the research is a daunting outing.

A: At this point, I am not aware of studies that can accommodate the most severely affected patients. This is a sad and recognized limitation of this research. Once we learn more, perhaps we can investigate how little it takes to trigger PEM?

 

Q: Is it possible to do some of this testing in other places? What would be required? Equipment, training etc

A: Yes, we could design multi-site studies. It would require a significant funding level of course, but they could be done.

 

Q: Is there a difference in these tests if the person is new to the disease or someone who has had the disease a long time?

A: A great question and one we (and others) are interested in. At this point, we do not know.

 

Q: Is there any hope of a study to make sure that men show the same problems as women (i.e., that diagnosis and treatment should be the same for both)?

A: Mary Ann Fletcher just received an RO1 to look at sex differences in ME/CFS.

 

Q: Talk about the difference between post-exertional malaise and post-exertional relapse.

A: At this point, we don’t know the laboratory differences. Perhaps expert physicians would know the clinical differences?

 

Q: This is fabulous–the best webinar for me to share with family and friends to make them familiar with the condition. It would make it even better if it could be stated and printed in the PowerPoint that exercise tests are made to approximate the activities of daily living that cause PEM. I have had people respond with “just don’t exercise that hard.”

A: Thank you. I’m glad it was useful. My response to people who say “don’t exercise that hard” would be that research has shown that even light activity can result in a worsening of symptoms and to be honest we don’t know how much is too much.

 

Q: Were people in study suffering from ME/CFS only or have other medical conditions that may contribute to PEM? I am very healthy other than suffering from ME/CFS and PEM is one of the most severe symptoms, mentally and physiologically, I experience!

A: All patients had ME/CFS and no other medical explanation for their symptoms or intolerance for exercise.

 

Q: Does PEM typically have detrimental effects on the immune system?

A: The research to date suggests that PEM does affect the immune system. Some data suggest that these responses are detrimental, but there is much more we need to learn about the consequences of the changes that we are seeing.

 

Q: You mentioned brain inflammation, is there any way you have to measure that?

A: There are some neuroimaging techniques that get at brain inflammation. For example, MR Spectroscopy can be used to look at certain molecules in the brain that are indicative of brain cell health that might be related to brain inflammation.

 

Q: Do you find a delay in the response, at least in symptoms after the exercise?

A: There is research to suggest that symptom worsening can be delayed for many days. There is other research that shows symptoms get worse the day of exertion and stay bad for several days. We need more research to understand this variability better.