Tag: 2018

Transient Receptor Potential Ion Channels in the Etiology and Pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling condition of unknown cause having multi-system manifestations. Our group has investigated the potential role of transient receptor potential (TRP) ion channels in the etiology and pathomechanism of this illness. Store-operated calcium entry (SOCE) signaling is the primary intracellular calcium signaling mechanism in non-excitable cells and is associated with TRP ion channels. While the sub-family (Canonical) TRPC has been traditionally associated with this important cellular mechanism, a member of the TRPM sub-family group (Melastatin), TRPM3, has also been recently identified as participating in SOCE in white matter of the central nervous system. We have identified single nucleotide polymorphisms (SNPs) in TRP genes in natural killer (NK) cells and peripheral blood mononuclear cells (PBMCs) in CFS/ME patients. We also describe biochemical pathway changes and calcium signaling perturbations in blood cells from patients. The ubiquitous distribution of TRP ion channels and specific locations of sub-family group members such as TRPM3 suggest a contribution to systemic pathology in CFS/ME.

Source: D. Staines, S. Du Preez, H. Cabanas, C. Balinas, N. Eaton, R. Passmore, R. Maksoud, J. Redmayne, S. Marshall-Gradisnik. Transient Receptor Potential Ion Channels in the Etiology and Pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. IJCM, Vol.9 No.5, May 2018. DOI: 10.4236/ijcm.2018.95038 

OMF creates new Harvard ME/CFS Collaborative Research Center and expands Stanford Data Center

From Open Medicine Foundation

We are proud to announce that OMF has funded $1.8 million for the establishment of a new ME/CFS Collaborative Research Center at the Harvard Medical School affiliated hospitals, which includes Massachusetts General Hospital (MGH), Brigham and Women’s Hospital, and Beth Israel Deaconess Medical Center.

The new Harvard Center will be led by OMF Scientific Advisory Board members Ronald G. Tompkins, MD, ScD, and Wenzhong Xiao, PhD, of Harvard University and will work synergistically with the ME/CFS Collaborative Research Center at Stanford led by Ronald W. Davis, PhD, of Stanford University, also funded by OMF. All science funded by OMF continues to be under the overall direction of our Scientific Advisory Board, directed by Ron Davis.

The goals for this new Harvard Collaborative Center are twofold. First is a basic research goal: to collect molecular data on muscle and other tissues affected by ME/CFS. Studies will include evaluation of patient muscle biopsies as compared to controls including genomics, proteomics, and ultrastructural analysis. Dr. Tompkins has extensive experience with such analysis on tissue from burn patients. He will be able to perform muscle biopsies, and possibly biopsies of other tissue types, greatly expanding the research, which has so far involved the analysis of blood cells. One focus of this new work will be to investigate the etiology of Post-Exertional Malaise (PEM).

The second goal is to establish a Clinical Trials Network to facilitate multi-center clinical studies on potential effective treatments for ME/CFS. The clinical resources at the MGH under Ron Tompkins, MD, are very extensive, making this an ideal site for overseeing and conducting clinical studies. This is a great opportunity to establish standards and the infrastructure for rigorous clinical trials.

Stanford ME/CFS Data Management and Coordination Center:

OMF is also funding the expansion of the Stanford Data Center for the Severely Ill Patients (SIPS) Study to encompass all the data from the Stanford and Harvard ME/CFS Collaborative Research Centers, as well as data from any other research we are funding.

The clinical results from the SIPS are currently already open to researchers with access via our website. This expanded data center will give researchers quick access to massive amounts of research data.

“These are exciting and important steps forward in our work to end ME/CFS, which we were able to take thanks to the dedication and donations of our many supporters. Thank you all for helping to make this possible and for being our partners in the urgent effort to put an end to this devastating disease.” – Linda Tannenbaum, CEO/President

Comparing Post-Exertional Symptoms following serial exercise tests

Abstract/Artist Statement:

Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functional ability. Recognizing the triggers, onset, symptoms and duration of PEM is important for the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM following serial exercise tests has not been examined.

PURPOSE: To compare descriptions of symptoms by ME/CFS and control subjects after two maximal exercise tests, each separated by 24 hours.

METHODS: Open-ended questionnaires were provided to 10 control subjects and 49 ME/CFS patients who underwent two maximal exercise tests, 24 hours apart. Each subject evaluated how they felt immediately after the first exercise test, before and immediately after the second exercise test, 24 hours after the second exercise test and in the week following the tests. Responses were analyzed and categorized by two reviewers, blinded to subject diagnosis.

RESULTS: Over the two days of testing, ME/CFS subjects reported an average of 15.4±7.7 symptoms compared to 5.5±1.8 in the control group. Following the tests, ME/CFS subjects reported an average of 5.0±2.8 symptoms compared to 0.1±0.3 in the control group. Among the ME/CFS subjects, fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. Out of the eighteen symptom categories, ME/CFS subjects reported seventeen at a higher frequency than control subjects. The largest differences were observed in cognitive dysfunction, headache, light-headedness, muscle/joint pain and weakness. Other symptoms included decreased function, pain, flu-like and gastrointestinal symptoms. Forty-nine percent of ME/CFS subjects recovered within an average of 4.5 days while fifty-one percent had not recovered by day seven. In contrast, all but one control subject recovered within 1 day.

CONCLUSION: A standardized exertional stimulus produces prolonged and more diverse symptoms in ME/CFS subjects compared with those seen in control subjects. Understanding PEM more comprehensively may provide clues to the underlying pathophysiology of ME/CFS and lead to improved diagnosis and treatment.

Source: Lariel J. Mateo, University of the Pacific. Comparing Post-Exertional Symptoms following serial exercise tests. Poster presentation, April 4, 2018. https://scholarlycommons.pacific.edu/purcc/2018/events/87/

May 12 Letter to the World Health Organization

Note: Following is a letter sent to the WHO by The International Alliance for M.E. to increase international recognition of and funding for ME/CFS. You can read a PDF file of the letter HERE.

Dr Tedros Adhanom Ghebreyesus
World Health Organisation
Avenue Appia 20
1202 Geneva

11 May 2018
CC Dr Svetlana Akselrod, Assistant Director General for Non-Communicable Diseases and Mental Health

Dear Dr Tedros

Urgent action to address M.E. globally: a neglected NCD

Tomorrow, on 12th May, people across the globe will come together in public spaces, at government buildings, online and in their homes to ask: ‘Can you see M.E. now?’ You can see their films, photographs and stories, shared for this global M.E. Awareness Day event, at  http://www.facebook.com/MEActNet and www.twitter.com/IAforME

M.E. (Myalgic Encephalomyelitis) is a complex, disabling, chronic, fluctuating, neurological condition of unknown aetiology. It is sometimes diagnosed as Chronic Fatigue Syndrome or CFS/M.E. It is a disease which affects 20,000,000 individuals of all ages and from all
ethnic groups – and the families around them – causing significant personal, social and economic hardship.

The US government’s landmark report, Beyond M.E./CFS: redefining an illness, made it clear that M.E. is ‘a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients. In its most severe form, this disease can consume the lives of those whom it afflicts.’1

M.E. is associated with neurological, immunological and energy-metabolism impairment, and is characterised by significant disability and a widespread intolerance to even small amounts of
mental and physical exertion. Other symptoms include sleep dysfunction, dizziness, widespread pain, cognitive dysfunction, and sensitivity to light and sound. We know that:

* one in four people with M.E. are so severely affected that they are unable to leave their beds or homes, sometimes for many years, too ill to bear even the touch of a loved one
* M.E. has the lowest health-related quality-of-life score when compared to cancer, diabetes, lupus, stroke, heart disease and chronic renal failure2
* people with M.E. are at an increased risk of cancer, heart disease, and suicide3
* in children and young people, the disease is the most common cause
of long-term school absence.4

Despite this suffering and disability, and the urgent need to find effective treatments, only 0.02% of international mainstream research funding has been directed towards M.E.5 Moreover, the condition is frequently undiagnosed, misdiagnosed and/or mistreated by physicians and often not recognised by national treatment and health insurance systems.

The International Alliance for M.E.’s awareness event on 12th May in Geneva, just one of thousands of Millions Missing6 events across the world, is part of our work to highlight the challenges faced by people with M.E.

We would greatly appreciate it if you could make time in your busy schedule to meet representatives from the International Alliance for M.E., a new collaboration uniting M.E. organisations in the US, Australia, Spain, Japan, South Africa and the UK. We would like to highlight the serious and significant impact of this often unrecognised condition, and explain why we are seeking urgent national and international action to increase research on the condition and ease the suffering of patients around the world.

We hope that, with the support of Members States and WHO, we will:

1. Recognise M.E. as a ‘serious, chronic, complex, and multisystem disease that frequently and dramatically limits the activities of affected patients’7 and adopt measures to provide a global and co-ordinated public health response to it.
2. Put in place transparency and a consultation process with M.E. organisations and patients on decisions related to M.E.
3. Support accelerated biomedical research to develop better diagnostic methods and treatments for M.E.
4. Ensure appropriate medical education for professionals working with M.E. patients.

As advocates, organisations, patients and carers, the International Alliance for M.E. is determined to see the condition properly recognised and treated, working with scientists and researchers across the world. We very much hope for your support for people living with M.E.

In the hope of your favorable reply to our invitation to meet,

Yours sincerely

The International Alliance for M.E.
ACAF – Associacio Catalana d’Afectades i Afectats de Fibromialgia i d’altres Sindromes de Sensibilitzacio Central, Spain
Action for M.E., United Kingdom
The American ME and CFS Society, United States
Emerge Australia, Australia
Forward ME, United Kingdom
Japan ME Association, Japan
ME CFS Foundation South Africa, South Africa
Plataforma Familiars Fm-SFC-SQM, Spain
Solve ME/CFS Initiative, United States

With support from
Association du Syndrome de Fatigue Chronique, France
Lost Voices Stiftung (Foundation), Germany
#MEAction, United Kingdom
ME/CFS Association Switzerland/Verein ME/CFS Schweiz, Switzerland
ME/FM Society of BC, Canada
ME Research UK, United Kingdom
Millions Missing Canada, Canada
Millions Missing France, France
National ME/FM Action Network, Canada
Open Medicine Foundation, United States
Welsh Association of ME & CFS Support (WAMES), United Kingdom

——–
1 Institute of Medicine (2015) Beyond M.E./CFS: redefining an illness
http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx
2 Hvidberg et al (2015) The Health-Related Quality of Life for
Patients with ME/CFS. PLoS ONE
3 Dimmock at al (2016) Estimating the disease burden of ME/CFS in the
United States and its relation to
research funding. Journal of Medicine and Therapeutics
4 Dowsett and Colby (1997) Long-term sickness absence due to ME/CFS in
UK schools; an epidemiological
study with medical and educational implications. Journal of Chronic
Fatigue Syndrome
5 Chowdhury and Radford (2016) M.E./CFS research funding
http://www.actionforme.org.uk/uploads/pdfs/mecfs-research-funding-report-2016.pdf
6 https://millionsmissing.meaction.net
7 Institute of Medicine (2015) Beyond M.E./CFS: redefining an illness
http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx

——–
(c) 2018 IAME

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis

Abstract:

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways.

In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop.

This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

Source: Morris G, Stubbs B, Köhler CA, Walder K, Slyepchenko A, Berk M, Carvalho AF. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev. 2018 Apr 4. pii: S1087-0792(17)30152-1. doi: 10.1016/j.smrv.2018.03.007. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29759891

Markey Leads Resolution Recognizing ME/CFS

Press Release: Washington (May 15, 2018) – Senator Edward J. Markey (D-Mass.) was joined by Senators Chris Van Hollen (D-Md.), Angus S. King Jr. (I-Maine), and Susan Collins (R-Maine) in introducing a Senate resolution recognizing May 12 as International Awareness Day for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). ME/CFS is a chronic, debilitating condition without a known cause, diagnostic, treatment, or cure. It may affect up to 2.5 million Americans and is estimated to be four times more prevalent in women than in men. ME/CFS costs the economy up to $24 billion a year, due to medical expenses and loss of productivity.

“ME/CFS has been in the shadows for too long,” said Senator Markey. “Our resolution is just one step to help shine light on this condition and what we can collectively do to help improve the quality of life of those impacted. I am inspired by the commitment from individuals living with ME/CFS and their loved ones to change the trajectory of this disease, and am honored to help raise awareness of their efforts with Senators Van Hollen, King, and Collins with this resolution.”  

Over the last several years, the National Institutes of Health (NIH) reorganized the Trans-NIH ME/CFS Working Group. Last year, the NIH awarded more than $7 million in grants to help establish Collaborative Research Centers and a Data Management Coordinating Center to enhance and coordinate research initiatives for ME/CFS throughout the NIH.

You can read the full resolution HERE.

Millions Missing Demonstrations – in Pictures

On May 12, 2018, Millions Missing demonstrations were held in over a dozen countries. Over 100 cities participated, bringing the plight of ME/CFS patients to the attention of media, public officials, and health organizations all over the world. The demands of Millions Missing are simple: Fund research, find a cure. Here is a small sampling of images from the May 12 protests. (You can find more photos HERE.)

 

UNITED STATES

Washington, DC

New York City

New York City

San Francisco

Los Angeles

Seattle

Morristown, NJ

Atlanta

UNITED KINGDOM

Southampton

London

Bristol

Manchester

Edinburgh, Scotland

EUROPE

Geneva, Switzerland

Copenhagen, Denmark

Bilbao, Spain

Helsinki, Finland

Gothenburg, Sweden

DOWN UNDER

Melbourne, Australia

Sydney, Australia

Christchurch, New Zealand

WORLD

Mexico City

 

Tokyo, Japan

Montreal Conference a Hit!

By Courtney Craig, D. C.

This May 3rd to May 5th marked the first annual Canadian Collaborative Team Conference at the CHU Sainte-Justine Hospital, Montreal. The conference brought together American and Canadian, patient and clinician, scientist and activist. Collaboration was indeed a major theme—with a focus on leveraging innovation to advance ME/CFS research. Day 1 introduced clinicians to the diagnosis and management of ME/CFS. Speakers stressed the importance of refining the diagnostic process. An accurate diagnosis was deemed the most important factor in patient care and in some cases is therapeutic. Canadian Clinicians presented a unique multidisciplinary approach with the establishment of large centers focused on the complex multi-system needs of patients.

A research-heavy day followed with parallel patient-centered sessions. Here, advocacy groups came together to brainstorm new projects in a post-Unrest ME/CFS world. Projects beyond May 12th and Millions Missing were suggested to continue the campaign throughout the year. Medical school education, leveraging technology and social media, legislative persistence, and education events targeted to industry, lawmakers, and philanthropists were all suggested.

Continue reading “Montreal Conference a Hit!” →

Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Prior research has found a heightened risk of suicide in patients with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). It is possible that a number of factors including stigma, unsupportive social interactions, and severe symptoms could lead to the development of depression, suicidal ideation, and heightened risk of suicide in this patient population. Prior studies have indicated that patients often report the legitimacy of their illness being questioned by family, friends, and even their physicians. This study aimed to determine whether stigma experienced, social support, symptomology, and functioning may be associated with depression and endorsement of suicidal ideation (SI) in patients with a self‐reported diagnosis of ME or CFS.

Findings indicated that participants that endorsed both SI and depression, in contrast to those that did not, experienced more frequent unsupportive social interactions in the form of blame for their illness, minimization of its severity, and social distancing from others. In addition, 7.1% of patients with ME and CFS endorsed SI but do not meet the criteria for clinical depression. These findings highlight the importance of stigma and unsupportive social interactions as risk factors for suicidal thoughts or actions among patients with ME and CFS. Community psychologists have an important role to play in helping educate health care professionals and the public to these types of risk factors for patients marginalized by ME and CFS.

Source: Stephanie L. McManimen, Damani McClellan, Jamie Stoothoff, Leonard A. Jason. Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome. Journal of Community Psychology, May 2018. https://doi.org/10.1002/jcop.21984

VIDEO: M.E. and me | BBC Newsbeat

ME sufferer Emma Donohoe investigates how young people cope with the debilitating illness, of which symptoms can include devastating fatigue, digestion issues and brain fog. It comes as current treatments for the condition are being reviewed, after years of controversy.