Telebriefing on NIH Research - November 28, 2017

"We request your participation in a telebriefing about updates on NIH’s efforts to advance research on ME/CFS. The telebriefing will be held on November 28, 2017, 1:00 until 2:00 pm ET. If you will be calling from the U.S., please use the following dial-in information for the telebriefing.

Dial-in: 877-951-7311

Participant passcode: 8394694

If you will be calling from another country, please see the attached chart for your country’s access information.

Please remember to register at NIHME CFSWorkingG@ninds.nih.gov if you plan to participate in the call.

Thank you in advance for your participation and we look forward to an engaging, thoughtful and productive conversation.

Regards,

The Trans-NIH ME/CFS Working Group"

Dial in numbers:

Country Toll Numbers Freephone/Toll Free Number

ARGENTINA 0800-444-1896

AUSTRALIA ADELAIDE: 61-8-8121-5055 1-800-010-717

AUSTRALIA BRISBANE: 61-7-3102-2044 1-800-010-717

AUSTRALIA CANBERRA: 61-2-6100-0106 1-800-010-717

AUSTRALIA MELBOURNE: 61-3-9010-0855 1-800-010-717

AUSTRALIA PERTH: 61-8-9467-5283 1-800-010-717

AUSTRALIA SYDNEY: 61-2-8209-1532 1-800-010-717

AUSTRIA 43-1-92-81-451 0800-005-806

BELGIUM 32-2-400-9848 0800-3-8930

BRAZIL RIO DE JANEIRO: 55-21-40421496 0800-7610645

BRAZIL SAO PAULO: 55-11-3958-0781 0800-7610645

CANADA 866-845-8494

CHILE 1230-020-5992

CHINA CHINA A: 86-400-810-4797 10800-712-2420

CHINA CHINA B: 86-400-810-4797 10800-120-2420

COLOMBIA 01800-9-157003

CROATIA 080-08-06-427

CZECH REPUBLIC 420-2-25-98-56-30 800-700-242

DENMARK 45-7014-0293 8088-2749

EGYPT 0800000-9038

ESTONIA 800-011-1105

FINLAND 358-9-5424-7160 0-800-9-19768

FRANCE LYON: 33-4-26-03-51-63 080-510-2765

FRANCE MARSEILLE: 33-4-86-06-48-63 080-510-2765

FRANCE PARIS: 33-1-72-25-40-66 080-510-2765

GERMANY 49-69-2222-4865 0800-800-1421

GREECE 30-80-1-100-0646 00800-12-8037

HONG KONG 852-3001-3891 800-963-695

HUNGARY 36-1-700-8830 06-800-11161

INDIA BANGALORE: 91-80-61275233

INDIA MUMBAI: 91-22-61501664

INDIA NEW DELHI: 91-11-66482046

INDIA INDIA A: 000-800-852-1135

INDIA INDIA B: 000-800-001-6247

INDIA INDIA C: 1800-300-00495

INDONESIA 007-803-011-0174

IRELAND 353-1-506-0476 1800-936-203

ISRAEL 1-80-9212610

ITALY MILAN: 39-02-3604-6280 800-977-455

ITALY ROME: 39-06-8751-6069 800-977-455

ITALY TORINO: 39-011-510-0169 800-977-455

JAPAN OSAKA: 81-6-7878-2602 0066-33-812361

JAPAN TOKYO: 81-3-6868-2602 0066-33-812361

LATVIA 8000-3204

LUXEMBOURG 352-27-000-1393 8002-9280

MALAYSIA 1-800-81-46854

MEXICO GUADALAJARA (JAL): 52-33-3208-7389 001-866-944-7679

MEXICO MEXICO CITY: 52-55-5062-9189 001-866-944-7679

MEXICO MONTERREY: 52-81-2482-0689 001-866-944-7679

NETHERLANDS 31-20-716-8076 0800-020-0351

NEW ZEALAND 64-9-970-4606 0800-456-270

NORWAY 47-21-590-025 800-18093

PANAMA 011-001-800-5072372

PERU 0800-53731

PHILIPPINES 63-2-858-3760 1800-111-42436

POLAND 00-800-1213476

PORTUGAL 351-2-10054734 8008-14928

ROMANIA 40-31-630-01-38

RUSSIA 8-10-8002-5594011

SAUDI ARABIA 800-8-110062

SINGAPORE 65-6517-0502 800-120-5213

SLOVAK REPUBLIC 421-2-322-422-79 0800-002025

SLOVENIA 0-800-81350

SOUTH AFRICA 080-09-82158

SOUTH KOREA 82-2-6744-1091 00798-14800-7797

SPAIN 34-91-414-21-70 800-300-907

SWEDEN 46-8-503-34-825 0200-899-946

SWITZERLAND 41-44-580-4320 0800-001-427

TAIWAN 886-2-2795-7391 00801-136-033

THAILAND 001-800-1206-66639

TURKEY 00-800-151-0818

UNITED ARAB EMIRATES 8000-35702389

UNITED KINGDOM BIRMINGHAM: 44-121-210-9183 0808-238-9817

UNITED KINGDOM GLASGOW: 44-141-202-0813 0808-238-9817

UNITED KINGDOM LEEDS: 44-113-301-0013 0808-238-9817

UNITED KINGDOM LONDON: 44-20-7950-1322 0808-238-9817

UNITED KINGDOM MANCHESTER: 44-161-601-0113 0808-238-9817

URUGUAY 000-413-598-3832

USA 1-203-607-0666 877-951-7311

VENEZUELA 0800-1-00-3644

VIETNAM 120-11747

Restrictions may exist when accessing freephone/toll free numbers using a mobile telephone.

PASSCODE: 8394694

Komaroff summary of 2016 IACFS/ME meeting

The IACFS/ME (International Association for CFS and ME) Conference is held every other year. This year it was held on October 27-30, at the Westin Fort Lauderdale Beach Resort in Fort Lauderdale, Florida.

This conference is a huge event, attracting researchers and clinicians from all over the world. There are workshops, presentations, poster sessions and numerous networking events. It is an exciting gathering, and a wonderful opportunity to hear the latest in ME/CFS research.

Traditionally, Dr. Komaroff gives a summary of the notable research presented at the conference. 

Mary Schweitzer has generously provided the summary below with this note: This is my best effort of transcribing Komaroff’s summary of the 2016 meeting - feel free to repost.

-----------------------------------------------------------

Komaroff summary of 2016 IACFS/ME meeting

In the past two years, since the 2014 SF meeting the report of the IOM based on a review of other 9.000 published articles concludes that ME/CFS is a “biologically-based illness”

Announcement of expanded research activities by the National Institutes of Health and educational efforts by the Centers for Disease Control and Prevention.

Evidence from this meeting of a biologically-based illness:

Studies of:
- Post-exertional malaise
- Immunologic findings
- Microbiome studies
- Brain and nervous system studies
- Epigenetic studies
- Energy metabolism
- Miscellaneous
- Diagnosis and treatment

Studies of post-exertional malaise (PEM)

Detailed analysis of the components of “post-exertional malaise” (Stanford)
- Physical and cognitive exertion trigger PEM more often than emotional distress.
- PEM includes not only fatigue, but also cognitive difficulties, sleep disturbances, headaches, muscle pain and flu-like symptoms
- PEM lasts 3 or more days in approximately 25% of people.

Exercise testing in patients with ME?CFS vs. healthy controls:
- Triggers a characteristic gene expression “signature” involving 15 cytokines/adipokines/growth factors (Stanford)
- When repeated 24 hours after a first exercise test leads to a significant decline in peak heart rate (“chronotropic incompetence”), which could contribute to post-exertional malaise (U of the Pacific)
- Leads to postural tachycardia after exercise (as contrasted to after tilt table testing) in a subset of ME/CFS patients and Gulf War Illness patients, due to increased sympathetic activity (Georgetown)

Exercise testing in patients with ME/CFS vs. healthy control subjects:
- Leads to lower oxygen consumption and earlier conversion to anaerobic metabolism (Nova and Wisconsin)
- Blood lactate levels in 2nd exercise test after 24 hours
- ME/CFS patients lactate levels are higher at all work loads
- Healthy controls: lactate leels are lower at all work loads.

Immunology:

Huge study: 192 cases, 392 healthy controls.
- Levels of 17/51 cytokines/adipokines/growth factors were significantly different in ME/CFS than healthy controls
- Most of the cytokines were pro-inflammatory, and their levels correlated significantly with the severity of symptoms (Stanford University)

Interesting because many clinicians and researchers in this field have long believed that the disease was caused by abnormal cytokines in the brain.

The errant B cell:
- The early rituximab studies, indicating therapeutic benefit in some patients (Bergen, Norway)
- Reduced diversity and increased clonality of B cells in ME/CFS
(NCNP, Japan)


Microbiome;

How the Microbiome may affect the brain
- The human microbiome: 10 times as many bacterial cells as human cells, containing 5-8 million genes compared to our 20,000+ genes

Microbes in our gut:
- Synthesize hormones and neurotransmitters (e.g. norepinephrine, serotonin, dopamine, Ach, GABA)

- Synthesize molecules of inflammation (cytokines, prostaglandins) and elicit the production of those molecules by the gut immune system
- Through inflammation, create a “leaky gut”: the tight junctions that bind gut epithelia cells together become loosened – allowing bacteria and bacterial toxins to enter the blood.

In addition to the recently-reported reduction in bacterial diversity in ME/CFS, the team reports finding an increased number of Caudovirales bacteriophage viruses in ME/CFS.

All of these findings point to low-level inflammation in the gut. (Cornell)

--------------

Brain and Nervous System

- Impaired speed in processing information is shown to be a critical deficit in both ME/CFS and Gulf War Illness
- Compared to healthy children, pediatric patients with ME/CFS had impaired information processing speed and attention. After exertion, these deficits worsened and ME/CFS kids also had poorer performance on tasks of working memory.
- Impairments in cerebral blood flow and cortical glutathione levels – not affected by comorbid psychiatric disease.
- A third of ME/CFS, but no healthy controls, had high white cell count or elevated protein in spinal fluid.
- Altered heart rate variability, due to reduced cardiac vagal activity, in ME/CFS v. healthy controls. [There is some evidence that this can be a sign or contributory factor to heart disease later.]

Functional connectivity among different brain regions impaired:
- Followed a cognitive test in ME/CFS v. healthy controls, determined by PET
- As determined by diffusion MRI in GWI patients
- As determined by EEG (eLORETTA) in ME/CFS patients at rest

----------------

Epigenetic studies

- Disease is caused not just by mutated genes
- It also is caused by perfectly normal, non-mutated genes, when those genes are not “expressed” (turned on or off) appropriately
- Gene expression is controlled by many different “epigenetic” forces
- Epigenetic studies are increasingly being done in ME/CFS v. healthy control
- ME/CFS: genes involved in signal transduction are hypomethylated more often, whereas genes involved in cell differentiation/cell death are hypermethylated more often
- ME/CFS: significantly different gene expression patterns for genes, involved in immune regulation (JAK-STAT pathway), hormone regulation and mitochondrial dysfunction.
- Gulf War Illness: 19 related groups of genes (“functional modules”) were found to have significantly altered gene expression. Specific immunosuppressant and hormonal therapies were identified that might target these dysregulated genes, and possibly improve symptoms.
- ME/CFS patients, compared to healthy controls, have 13 different gene loci, all involving glucocorticoid sensitivity that are differentially methylated. The different methylation patterns correlated with clinical symptoms
- Characteristic expression of two particular microRNAs in plasma leads to elevated homocysteine levels identified in ME/CFS
- Three SNPs distinguished ME/CFS patients from healthy controls. All involve a gene that codes for a subunit of NADH dehydrogenase – an important energy molecule.
- MicroRNAs in spinal fluid predict orthostatic tachycardia after exercise.
- No clear gene expression differences in ME/CFS v. healthy controls, at rest.

----------------

Energy Metabolism Studies

- Studies on patients in the rituximab trial have an energy metabolism deficit, and the key molecule is the enzyme pyruvate dehydrogenase (PDH). Speculate that autoantiboedies may be the cause of this deficit. Upregulation of PDH inhibitors in white blood cells (Norway group – study will finish late 2017)
- Peripheral white blood cells from ME/CFS produce energy less well than WBCs from healthy subjects, particularly when the cells are exposed to stressors.
- Citric acid cycle metabolites are depleted. Glucose as an energy source is being replaced by fatty acids and amino acids
- “Unbiased” metabolomics study finds that the metabolites that are most different between ME/CFS and healthy controls involve pathways harvesting energy from glucose, fatty acids and amino acids.
- Also finds a general hypometabolic state, as did the recent paper from Naviaux (PNAS), though different metabolites were examined.

---------------------

Miscellaneous

- ME/CFS patients, but not healthy controls, experience a worsening of symptoms following true (but not sham) strain: neuromuscular strain (even sitting/driving for prolonged time) may contribute to symptoms of ME/CFS. Physical therapy likely to help
- Five specific findings on physical examination were quite accurate in diagnosing ME/CFS. This is of interest, since ME/CFS is defined exclusively by symptoms.
- Of over 200 single-nucleotide polymorphisms examined, three – all located in the gene for NADH dehydrogenases – were significantly different in ME/CFS patients than in healthy controls.
- ME/CFS patients have significantly higher anti-citrullinated protein antibodies than matched healthy controls, as is seen in the autoimmune whatever.
- Particular mutations in two nucleosome transport genes distinguish ME/CFS patients from healthy controls.
- A second case of ME/CFS caused by an enteroviral infection of the brain.
- Impressive hypothesis: dysregulation in the production/release of Hydrogen Sulfide could explain many of the symptoms and objective abnormalities seen in ME/CFS
- A subset of ME/CFS patients with sinusitis and/or hives has more pain and other symptoms

Possible Diagnostic Tests for ME/CFS?

Four biomarkers – IL-8, sCD14, PGE2 and CD3/CD57+ count – correctly predicted ME/CFS in 97% of female cases (UNR)

An ideal diagnostic test would:
· Have very low false positive and false negative rates, compared to healthy controls and other fatiguing disease, when retested on a large number of new people
· Be easy for perform reliably by many labs
· Be inexpensive

Treatment Studies

· MRI spectroscopy revealed 15% lower levels of the natural antioxidant, glutathione, in the brain in ME/CFS patients compared to controls. N-acetyl-cysteine (NAC) treatment improved both brain
glutathione levels and symptoms, and reduced oxidative stress, in the ME/CFS patients
· Randomized trial of low-dose methylphenidate plus a nutritional regimen designed to improve mitochondrial function. At 12 weeks, a trend toward reduced symptom that was not statistically significant; more severely ill patients seemed to benefit
· A careful study of 990 ME/CFS patients found that patient beliefs about the cause of their illness did not explain their level of activity, a result that does not support the theoretical benefit of cognitive behavioral therapy.
· Multimodel physical therapy improves symptoms in adolescents and young adults with ME/CFS and impaired range of motion.
· Quantitative modeling identifies drug that are already FDA-approved and that might target TNA-alpha, IL-2 and the glucocorticoid receptor – targets that may be important in causing the symptoms of GWI

Multisite consortia to standardize and pool clinical and biosample data
· CDC: Multi-Site Clinic Assessment (MCAM), with 7 collaborating centers. Biospeci and other things.

Questions addressed by many presentations:
· In an illness defined exclusively by subjective symptoms, is there evidence of underlying biological abnormalities?
· Could those biological abnormalities theoretically explain the symptoms?
· Do the abnormalities in fact correlate with the symptoms?

In Summary:

Case-control studies comparing patients with CFS to both disease comparison groups and healthy control subjects find robust evidence of:
· the brain and autonomic nervous system
· immune system
· energy metabolism
· oxidative and nitrosative stress

The illness is not simply the expression of physical symptoms by people with a primary psychological disorder.

[Komaroff believes that new methods are getting us closer, quicker. Also the exercise evidence is changing the way people do research.]

Chasing Competent Care Conference Report

By Sally Burch

Hope 4 ME & Fibro Northern Ireland ran an ambitious and exciting conference on Monday 6th June in The Stormont Hotel, Belfast.  The conference, “Chasing Competent Care” delivered a strong message calling for change to the currently inadequate care situation for ME and fibromyalgia patients in Northern Ireland.

Chairperson, Martina Marks opened the meeting, welcomed everyone and thanked the Big Lottery Fund for their sponsorship of the event. Her welcome was followed by an impassioned plea from Joan McParland, the founder and treasurer of Hope 4 ME & Fibro NI, to have medical professionals take patients’ symptoms seriously.  Joan explained that she had been ill, and operating at less than 30% of her normal capacity, since 1999. In that time no effective treatments had been offered, and one consultant had even suggested she was simply reading too much into her symptoms and that she should see a psychiatrist!

Joan thanked the many volunteers and family members who made the event possible, and also the medical professionals and MLAs in the audience for taking time to attend.

Sally Burch, another charity trustee, then pointed out that ME (myalgic encephalomyelitis) and fibromyalgia are both disorders recognised by the World Health Organisation. She then explained that the most severely affected by ME could be left bed-bound, tube fed and lying in darkened rooms for weeks, months and years! She further described the severely debilitating nature of fibromyalgia and how the invisible pain that sufferers endure can have devastating life consequences. Sally outlined the symptom overlap between these conditions and suggested that biomarker development and medical research was now urgently required.

Lined up, to the side of the speakers’ podium, was a haunting display of over 200 pairs of empty shoes. These were part of the global #MillionsMissing campaign. Each pair of shoes carried a tag with the name of a patient unable to participate in their active lives due to ME and/or fibromyalgia.  During the conference many attendees took time to read the comments on the tags and to consider the magnitude of the devastation caused by these largely forgotten and ignored conditions.

Joe McVeigh

First speaker up was Dr. Joe McVeigh, who outlined the problems with exercise and fibromyalgia. He explained that whilst exercise is important for maintaining health, that it must be conducted at a level manageable for each individual patient. He called this the “Goldilocks approach”, and explained that at no time should attempted exercise cause a patient to relapse.

Professor Malcolm Hooper next gave a strong talk berating the inadequacies and misleading conclusions of the PACE Trial.  At one point, he suggested that the PACE Trial was potentially fraudulent and told us that he had once even said as much in The House of Lords.  This elicited a spontaneous round of applause from the audience. Feelings run high amongst patients on the PACE trial, mostly because it has been used to support the NHS recommended therapies of Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET), both of which have been demonstrated to cause harm in patient surveys.

Malcolm Hooper

Professor Hooper questioned the motives of the PACE trial authors in promoting results that carry such marginal benefits and such great potential risks. He recommended that patients reference Mark Vink’s paper, “The PACE Trial Invalidates the Use of Cognitive Behavioral andGraded Exercise Therapy in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome:A Review,” any time they were asked to undertake these therapies.

After this lively and well received talk, the conference paused for a comfort break. The weather was uncharacteristically balmy for Northern Ireland, and some of the audience sat outside in the evening sun as they contemplated the issues raised.

Natalie Boulton, carer to her daughter who has severe ME, spoke next.  She opened by showing a clip from the video “Voices from the Shadows”, that gave the audience a disturbing insight into the annihilation caused by very severe ME.  Natalie told us she had recently followed up with some of the patients from the video and found many of them had worsened, and that both Emily Collingridge and Lyn Gilderdale had since died. She spoke of the horror of the treatments doled out by psychiatrists who believed patients to be faking their illness. Hers was a genuinely moving and sobering talk.

Next Professor Mady Hornig from Columbia University, USA, gave a detailed and highly informative account of her work towards developing blood biomarkers.  She explained how immunity and gut microbiota can be linked to the brain, its functioning and mood.  She talked about the epigenetic changes that can occur in the microbiome during a person’s lifetime and the link to serotonin production. She also talked about measuring blood molecules such as cytokines before and after an exercise challenge in ME patients, and comparing these changes to healthy controls. These cytokines being the most promising as potential biomarkers. Although much of what she described cannot be simply summarised, the audience was left with a strong feeling that Professor Hornig is now working determinedly to solve the biochemical riddles produced by ME.

Pamela Bell

Dr. Pamela Bell then took the podium to talk about the problem with pain. Dr. Bell has worked extensively in the field of pain, and is now chair of the Pain Alliance Northern Ireland. She emphasised the widespread nature of chronic pain and its disabling effects, noting that once pain becomes chronic it no longer serves a useful purpose in the body. She recognised the difficulties with effectively treating ongoing pain and explained that different types of pain needed different drug types to alleviate symptoms.

The final speaker of the evening was Louise Skelly from the Patient and Client Council of Northern Ireland.  She spoke of her frustration at trying to bring about change to the current impasse with Health and Social Care Board in Northern Ireland regarding the care on offer for ME and fibromyalgia patients. She spoke of her determination to follow through with the campaign to improve the situation, and of the great need of these neglected patient cohorts.

Martina Marks then brought the conference to a close. Overall the atmosphere of the evening was one of both frustration, and of optimism. Frustration that change seems to be taking so long to happen and for the injustices that have occurred along the way, but also optimism that things are starting gain momentum towards real medical advances for the future.

As the hall emptied, the lines of lonely shoes from the #MillionsMissing campaign were gathered up, their labels still attached, and some-one was heard to say: “These are the folk we do all this for, they will not be left forgotten any longer.”

____________________

Please consider using this link for all your online shopping and raise funds for Hope 4 ME & Fibro Northern Ireland at NO charge to you!

https://www.giveasyoulive.com/refer

Bio-ethics and ME tweet chat on April 7th

The following message is from @Katiissick

There will be an open twitter chat on bioethics and ME on April 7, at 8:30 PM Eastern time (5:30 PT) thanks to Jennifer Chevinsky, a medical student who hosts a weekly bioethics chat on Twitter.

These chats attract health care professionals, ethicists, and the general public. You are welcome to join in the dialogue and share your ideas. All you need is a twitter account! It is an opportunity to raise awareness, and there are big chances that many will learn about ME and its devastation at the personal and societal levels.

The April 7 chat is focused on the following questions:

1. Are there ethical or societal effects of calling the disease Myalgic Encephalomyelitis versus Chronic Fatigue Syndrome? How do disease names affect perceptions?

2a. Myalgic Encephalomyelitis is often misdiagnosed and/or mistreated. What additional harms can misdiagnosis and/or mistreatment expose individuals, healthcare professionals, and society to?

2b. A Patient with Myalgic Encephalomyelitis has been held in a Denmark psychiatric facility since February 2013 against her will. What conditions should be met to ethically commit a patient?

3a. Myalgic Encephalomyelitis is not 'rare,' but it can be considered unpopular. What makes (or should make) a disease more likely to get funding or research money?

3b. What makes (or should make) a disease more likely to be taught in medical education? How does it affect the patient population if it is not taught?

4. How can you, patients, health care professionals, and/or others help remove stigma from diseases such as myalgic encephalomyelitis? What's one thing you have learned tonight?

In order to participate in the chat, all of your tweets need to include #bioethx in them.

A few websites facilitate twitter chats, including www.tweetchat.com You will need a twitter account and login information, enter the hashtag (bioethx) and enter the virtual room.

There are many Twitter Chats related to health care. You can visit http://www.symplur.com/healthcare-hashtags/tweet-chats/ to look up the different chats and their schedules. Chats are also a great opportunity to increase your contacts outside our patient community and speak out about your experiences. Sunday evening's #HCSM (health care social media) are usually a lot of fun!

There are common sense rules when taking part in a tweet chat. 

1) Answer the questions with their number A1, A2a, A2B etc.

2) Stay on topic, and engage in the discussion.

3) Make sure you have the #bioethx in your tweet otherwise it is not seen by others in the chat or recorded. Other hashtag of use are #mecfs #neuroME #CDC #HHS #NIH #meded #hcldr (health care leaders)

Twitter can be powerful as you can direct advocacy to interest groups, like the NIH and CDC. For instance, Dr Frieden at the CDC has an account. The Center for Infection and Immunity (@CII722) (Columbia university) has a twitter account and tweets about ME. We can increase awareness by engaging with different groups and people outside our community. Twitter does that.

The chat will be recorded and will be available afterwards if you missed it. I will update as available.

Share widely and join us on April 7th at 8:30 EST!

Feel free to add me on twitter @Katiissick