NEW RESEARCH IN ME/CFS INVEST IN ME SPRING 2017 MAJOR CATEGORIES - - PowerPoint PPT Presentation

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NEW RESEARCH IN ME/CFS INVEST IN ME SPRING 2017 MAJOR CATEGORIES - - PowerPoint PPT Presentation

NEW RESEARCH IN ME/CFS INVEST IN ME SPRING 2017 MAJOR CATEGORIES 1. TISSUE/BRAIN BANK 2. COMMON DATA ELEMENTS 3. MICROBIOME/METABOLOME 4. AUTOIMMUNITY TISSUE/BRAIN BANK 1. NACAL & OTHERS, LONDON SCHOOL OF HYGIENE AND


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SLIDE 1

NEW RESEARCH IN ME/CFS

INVEST IN ME SPRING 2017

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SLIDE 2

MAJOR CATEGORIES

  • 1. TISSUE/BRAIN BANK
  • 2. COMMON DATA ELEMENTS
  • 3. MICROBIOME/METABOLOME
  • 4. AUTOIMMUNITY
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TISSUE/BRAIN BANK

  • 1. NACAL & OTHERS, LONDON SCHOOL OF
  • HYGIENE AND TROPICAL MEDICINE & NIAID
  • 2. ESTABLISH POST-MORTEM BRAIN AND

TISSUE BANK FOR STUDY OF ME/CFS

  • 3. ESTABLISH A SPECIFIC DONOR PROGRAM
  • 4. RAPID COLLECTION AND PROCESSING
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TISSUE/BRAIN BANK

  • 5. SUPPLEMENTAL CLINICAL, LAB AND SELF-

ASSESSMENT DATA COLLECTED FROM EACH POTENTIAL SUBJECT IN ADVANCE

  • 6. INCORPORATE INTO AN EXISTING BIOBANK

(CREUTZFELDT-JACOB DISEASE/ALZHEIMER’S)

  • 7. POTENTIAL DONORS ACCESS A WEB PAGE

AND FOLLOW INSTRUCTIONS

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TISSUE/BRAIN BANK

  • GOALS:
  • 1. SEEK TO ESTABLISH A COHORT OF WELL

CHARACTERIZED CONTROLS AND ME/CFS PATIENTS

  • 2. IDENTIFY POTENTIAL BIOMARKERS AND

RETRIEVE HIGH QUALITY PATHOLOGICAL SAMPLES

  • 3. DISSEMINATE THIS RESOURCE GLOBALLY
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COMMON DATA ELEMENTS

  • Jason LA, Unger ER, Dimitrakoff JD et al.

Minimum data elements for research reports in ME/CFS. Brain Behav Immun.2012 Mar;26(3):401-6.

  • ADDRESS PROBLEM OF VARIABILITY IN

ME/CFS RESEARCH; CRITICAL ELEMENTS THAT SHOULD BE INCLUDED IN NEW RESEARCH

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COMMON DATA ELEMENTS

  • 1. STUDY DESIGN:
  • a. type of study: case/control; longitudinal
  • b. demographics: age, race, ethnicity,

gender,duration of illness, disability status

  • c.case definition: ?multiple vs one
  • d. symptom inventory: frequency and severity
  • f case defining symptoms; sleep, pain,

include scoring methodology

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COMMON DATA ELEMENTS

  • e. use of self report scales: SF-36; sickness

impact profile

  • f. functional assesment: exercise testing
  • g. allostatic loads: heart rate variability, body

mass index; 24 hour urinary cortisol

  • h. test HPA axis, i.e. cortisol, ACTH
  • i. immune fx: nk studies, cytokines
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COMMON DATA ELEMENTS

  • j. sympathetic activity: salivary amylase
  • k. imaging: MRI, functional MRI, SPECT scan
  • l. genomic and transcriptomic studies:
  • Genome wide assessment studies; whole

genome sequencing; transcriptomal analysis (mRNA); epigenetic studies

  • m. proteomic studies: disease defining

markers

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MICROBIOME

  • Professor Simon Carding, Institute of Food

Research, Norwich Research Park, UK

  • Navaneethavaja N, Griffiths, V, Carding S, et al.

A role for the intestinal microbiota and virome in ME/CFS. J Clin Med. 2016 Jun;5(6)55.

  • 1. Breaks in gut epithelial mucosa help

transport elements of gut dysbyosis

  • 2. Link to diminished cognitive function in

ME/CFS patients

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MICROBIOME

  • 3. 77% of ME/CFS patients demonstrate small

intestinal overgrowth

  • 4. further examination of gut `virome’ which is

unique to the individual and less subject to change that bacterial species; bacteriophages transport viral particles into the gut

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METABOLOME

  • Fluge O, Mella O, et al. Metabolic profiling

indicates impaired pyruvate dehydrogenase function in ME/CFS. JCI Insight. 2016 Dec 22; 1(21):e89376

  • 1. Diminished number of amino acids that fuel
  • xidative metabolism via the tricarboxylic acid

cycle (TCA)

  • 2. Amino acid pattern shows impairment of

pyruvate dehydrogenase (PDH), key enzyme

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METABOLOME

  • 3. inadequate generation of ATP by oxidative

phosphorylation causes excessive lactate generation on exertion

  • 4. diminished glucose oxidation and increased

anaerobic metabolism with increased use of amino acids in the TCA cycle

  • 5. PDH dysregulation and changes in amino

acid metabolism provide one mechanism

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METABOLOME

  • 6. Other studies have shown diminished

sphingo-lipid and fatty acid metabolism

  • 7. PDH dependent metabolism is important in

exertional activity but may not be apparent when ME/CFS subjects are at rest

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AUTOIMMUNITY

  • Loebel M, Grabowski, P, Scheibenbogen C.

Antibodies to beta adrenergic and muscarinic receptors in chronic fatigue syndrome. Brain Behav Immun. 2016 Feb; 52:32-9.

  • 1. Infection triggered disease onset leads to

chronic immune activation and autonomic dysregulation suggesting autoimmune antibodies directed against neurotransmitter

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AUTOIMMUNITY

  • Receptors in ME/CFS patients
  • 2. in patients receiving Rituximab, B cell

depletion therapy, those patients who are responders will have diminished antibody to these receptors at the end of treatment