Stars Not Aligning Any More: CFS NIH Grant Panel (SEP) Reverts, McClure on Board

February 3, 2011

Posted by Cort Johnson

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CFS GRANT REVIEW (SEP) Meeting Roster – (2/22/2011 – 2/23/2011)

The last CFS SEP Panel, heavy with immunologists and other CFS researchers, was remarkably changed. (Unfortunately Dr. Klimas called the number of grant proposals was ‘pitiful’ – so it’s not clear how helpful they were.) The present panel is remarkably different from the last one and not in a good way. Now we have an in-between panel; it’s a mix of pain (FM ie dental) and CFS and other researchers. It’s better than most CFS SEP’s (a third of the researchers have some CFS research experience – but it’s mostly dominated by pain researchers again.

In contrast to other standing panels which have consistent membership the SEP panels are supposed to reflect the types of applications before them. (This often did not happen before and several researchers have publically complained of having immune grant proposals reviewed by people with other backgrounds.) Whether the new panel reflects more fibromyalgia grant applications coming in (the panel reviews both) or whether the last panel was the anomaly that reflected the heightened interest in XMRV is hard to tell. Some changes were expected since this is a FM/TMD panel as well but many of the bright CFS faces on the panel (Klimas, Broderick, Ruscetti, Fletcher are gone…Only Friedberg and Hanson remain.

We did pick up some CFS researcher support from Baraniuk, Boies and Theoharidies but two of these researchers have hardly been focused on CFS. It’s tough to lose researchers with broad experience in CFS and a history of research such as Klimas, Fletcher and Broderick) and replace them with people with more of a peripheral interest. Bizarrely, Dr. McClure showed up and she’s the only UK researcher on the panel. Dr. Hanson provides an offsetting viewpoint on XMRV but what a strange thing to have this lightning rod show up on a CFS grant review panel. (A message to the WPI?) As XMRV Global Action notes at one point she said would never have anything to do with this disease again.

It’s a interesting panel of researchers with a wide swath of experience. It shows, I would guess, where the NIH is going with this group of diseases (CFS, FM, IBS)….a mix of behavior and pathophysiology with a strong focus on the brain, the stress response, HPA axis and an indications that researchers across these disorders are looking at childhood stress/HPA axis interactions – as well as in ME/CFS.

CFS SCORECARD

  • Prominent ME/CFS Researchers – 1
  • Researchers with a bit of ME/CFS Experience – 4
  • Pain Researchers – 10

Researchers with CFS background Dr. Baraniuk – allergist, brain proteome (new paper shortly), spinal fluid ANS

Quote:
  • Relationships among rhinitis, fibromyalgia, and chronic fatigue. Baraniuk JN, Zheng Y.
  • Allergy Asthma Proc. 2010 May-Jun;31(3):169-78.
  • Xenotropic murine leukemia virus-related virus in chronic fatigue syndrome and prostate cancer. Baraniuk JN. Curr Allergy Asthma Rep. 2010 May;10(3):210-4.

Richard Bolesbelieves mitochondrial disorders cause CFS, FM, migraines, depression and other ‘affective somatic disorders’:

Quote:
  • Fatal infantile lactic acidosis and a novel homozygous mutation in the SUCLG1 gene: A mitochondrial DNA depletion disorder.
  • Beyond the serotonin hypothesis: Mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.
  • High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the “affective spectrum disorders”, and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders.
  • Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency

Maureen Hanson - mostly a plant biologist; primary focus has been studying RNA editing/binding in plant cells, now studying XMRV in CFS, awarded one of few NIH grants on XMRV in CFS, found similar findings to Alter/Lo.

Quote:
  • An efficient downstream box fusion allows high-level accumulation of active bacterial beta-glucosidase in tobacco chloroplasts. Gray BN, Yang H, Ahner BA, Hanson MR.Plant Mol Biol. 2011 Jan 30. [Epub ahead of print]
  • Chloroplast RNA metabolism. Stern DB, Goldschmidt-Clermont M, Hanson MR. Annu Rev Plant Biol. 2010 Jun 2;61:125-55. Review.

Myra McClure! - retrovirologist, published contamination XMRV paper and very, (very) early study finding no XMRV, public commentator on XMRV issues..only UK researcher on the panel..quite active in the field….balanced out by Hansen or not?

Quote:
  • Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFκB activation resulting in a microenvironment predisposed to ectopic pregnancy.Shaw JL, Wills GS, Lee KF, Horner PJ, McClure MO, Abrahams VM, Wheelhouse N, Jabbour HN, Critchley HO, Entrican G, Horne AW.
  • Mouse DNA contamination in human tissue tested for XMRV. Robinson MJ, Erlwein OW, Kaye S, Weber J, Cingoz O, Patel A, Walker MM, Kim WJ, Uiprasertkul M, Coffin JM, McClure MO. Retrovirology. 2010 Dec 20;7:108.
  • Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men. Thomson EC, Fleming VM, Main J, Klenerman P, Weber J, Eliahoo J, Smith J, McClure MO, Karayiannis P. Gut. 2010 Dec 7. [Epub ahead of print]

T Theonarides – major autism researcher, currently studying mast cell activation in CFS (as well as autism)

Quote:
  • Brief Report: “Allergic Symptoms” in Children with Autism Spectrum Disorders. More than Meets the Eye? Angelidou A, Alysandratos KD, Asadi S, Zhang B, Francis K, Vasiadi M, Kalogeromitros D, Theoharides TC. J Autism Dev Disord. 2011 Jan 6. [Epub ahead of
  • Theoharides TC, Angelidou A, Alysandratos KD, Zhang B, Asadi S, Francis K, Toniato E, Kalogeromitros D. Mast cells and inflammation.
  • Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, Asadi S, Vasiadi M, Weng Z, Miniati A, Kalogeromitros D.

L. Gerber - Cancer Fatigue and CFS - focus hard to tell; a mixture of pathophysiological factors and behavior/perception?

Quote:
  • Factors predicting clinically significant fatigue in women following treatment for primary breast cancer. Gerber LH, Stout N, McGarvey C, Soballe P, Shieh CY, Diao G, Springer BA, Pfalzer LA.Support Care Cancer. 2010 Sep 12. ( Findings - CSF at ≥9 months significantly correlated with BMI ≥ 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05).These are remediable. (by what? Exercise???)
  • Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome.
  • Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. PM R. 2009 Jul;1(7):620-8. (findings - This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued and have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity, and provide additional information about patients' perceptions)

Related Fields Lin Chang - main focus - pathophysiology of irritable bowel syndrome (IBS) with particular interests in the overlap of IBS with fibromyalgia, as well as gender differences and neuroendocrine alterations. She is all over the map co-authoring papers on everything from bacterial overgrowth to yes, childhood stress and the HPA axis..http://www.cns.med.ucla.edu/Bios/ChangL.htm

Quote:
  • Gastroenterology. 2011 Jan 19. The Role of Stress on Physiologic Responses and Clinical Symptoms in Irritable Bowel Syndrome.Diagnosis and management of IBS.Khan S, Chang L.Nat Rev Gastroenterol Hepatol. 2010 Oct;7(10):565-81. Review.
  • Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors? Spiegel BM, Chey WD, Chang L. Am J Gastroenterol. 2008 Dec;103(12):2972-6.
  • Childhood trauma is associated with hypothalamic-pituitary-adrenal axis responsiveness in irritable bowel syndrome. Videlock EJ, Adeyemo M, Licudine A, Hirano M, Ohning G, Mayer M, Mayer EA, Chang L. Gastroenterology. 2009 Dec;137(6):1954-62. Epub 2009 Sep 6.
  • Increased acoustic startle responses in IBS patients during abdominal and nonabdominal threat. Naliboff BD, Waters AM, Labus JS, Kilpatrick L, Craske MG, Chang L, Negoro H, Ibrahimovic H, Mayer EA, Ornitz E.

Mary Meagher - Effects of stress on viral activiation, neuroimmune factors

Quote:
  • Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity.Young EE, Sieve AN, Vichaya EG, Carcoba LM, Young CR, Ambrus A, Storts R, Welsh CJ, Meagher MW. J Neuroimmunol. 2010 Mar 30;220(1-2):79-89. Epub 2010 Feb 18.
  • Effects of stress on the immune response to Theiler's virus--implications for virus-induced autoimmunity. Welsh CJ, Steelman AJ, Mi W, Young CR, Dean DD, Storts R, Welsh TH Jr, Meagher MW.Neuroimmunomodulation. 2010;17(3):169-72. Epub 2010
  • Neuroimmune interactions in a model of multiple sclerosis. Welsh CJ, Steelman AJ, Mi W, Young CR, Storts R, Welsh TH Jr, Meagher MW.Ann N Y Acad Sci. 2009 Feb;1153:209-19. Review.

Pain Researchers - notice the focus on brain activation, stress and that several fields are exploring childhood stress/HPA axis alterations as well
Mary Davis - genetic basis for increased pain in FM, behavioral aspects pain/fatigue, cortisol - childhood maltreatment and pain, gender and pain

Quote:
  • COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.Finan PH, Zautra AJ, Davis MC, Lemery-Chalfant K, Covault J, Tennen H.Pain. 2011 Feb;152(2):300-7. Epub 2010 Dec 3. (findings provide support for genetic moderation of a maladaptive coping and pain process and suggest that genetic variation in the val(158)met polymorphism may affect fibromyalgia pain through pathways of pain-related cognition.)
  • Psychosom Med. 2010 Jun;72(5):471-80. Epub 2010 May 13. Childhood maltreatment and diurnal cortisol patterns in women with chronic pain. Nicolson NA, Davis MC, Kruszewski D, Zautra AJ. Health Psychol. 2010 Mar;29(2):134-42.
  • Genetic influences on the dynamics of pain and affect in fibromyalgia. Finan PH, Zautra AJ, Davis MC, Lemery-Chalfant K, Covault J, Tennen H.

Lucy Chen - physiological pain research -

Quote:
  • The Effect of Intrathecal Gabapentin on Pain Behavior and Hemodynamics on the Formalin est in the Rat

Dante Chialvo - brain networks - pain, sleep, environmental pollutants (!)

Quote:
  • Modular organization of brain resting state networks in chronic back pain patients.
Quote:
  • Balenzuela P, Chernomoretz A, Fraiman D, Cifre I, Sitges C, Montoya P, Chialvo DR.Front Neuroinformatics. 2010 Nov 17;4:116.
  • 2. Spike avalanches exhibit universal dynamics across the sleep-wake cycle. Ribeiro TL, Copelli M, Caixeta F, Belchior H, Chialvo DR, Nicolelis MA, Ribeiro S.PLoS One. 2010 Nov 30;5(11):e14129.
  • 3. The environmental pollutant endosulfan disrupts cerebral cortical function at low doses.Scremin OU, Chialvo DR, Lavarello S, Berra HH, Lucero MA.Neurotoxicology. 2011 Jan;32(1):31-7. Epub 2010 Dec 7.

Joel Greenspan - Pathophysiological Aspects of Pain, brain activation, neural pathways

Quote:
  • Differential brain activation associated with laser-evoked burning and pricking pain: An event-related fMRI study. Veldhuijzen DS, Nemenov MI, Keaser M, Zhuo J, Gullapalli RP, Greenspan JD. Pain. 2009 Jan;141(1-2):104-13. Epub 2008 Dec 5.
  • Identifying biological markers of activity in human nociceptive pathways to facilitate analgesic drug development. Chizh BA, Greenspan JD, Casey KL, Nemenov MI, Treede RD.Pain. 2008 Nov 30;140(2):249-53. Epub 2008 Oct 23. Review.
  • Quantitative somatic sensory testing and functional imaging of the response to painful stimuli before and after cingulotomy for obsessive-compulsive disorder (OCD).Greenspan JD, Coghill RC, Gilron I, Sarlani E, Veldhuijzen DS, Lenz FA.

Mark Holmberg - cortical response to stimulation, arousal in the brain

Quote:
  • Temporomandibular disorder modifies cortical response to tactile stimulation.
  • Nebel MB, Folger S, Tommerdahl M, Hollins M, McGlone F, Essick G.
  • J Pain. 2010 Nov;11(11):1083-94. Epub 2010 May 1

Linda Laresche - Gender and pain - calling attention to gender disparities and the need for more research...(little research herself)

Quote:
  • Clin Orthop Relat Res. 2011 Jan 6. [Epub ahead of print] Defining Gender Disparities in Pain Management.
  • Pain. 2010 Aug;150(2):309-18. Epub 2010 Jun 16.Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review. Popescu A, LeResche L, Truelove EL, Drangsholt MT.

Octavio Plesh – mostly epidemiological type research on TMD/FM. Worked with Buchwald on one study

Quote:
  • Temporomandibular joint and muscle disorder-type pain in U.S. adults: the National Health Interview Survey. Isong U, Gansky SA, Plesh O.J Orofac Pain. 2008 Fall;22(4):317-22.
Quote:
  • Are post-traumatic stress disorder symptoms and temporomandibular pain associated? Findings from a community-based twin registry. Afari N, Wen Y, Buchwald D, Goldberg J, Plesh O.

E Schiffman – TMD Diagnosis – not pathophysiological research

Quote:
  • Influence of headache frequency on clinical signs and symptoms of TMD in subjects with temple headache and TMD pain. Anderson GC, John MT, Ohrbach R, Nixdorf DR, Schiffman EL, Truelove ES, List T. Pain. 2010 Dec 31. [Epub ahead of print]
Quote:
  • Critical appraisal of methods used in randomized controlled trials of treatments for temporomandibular disorders.Fricton JR, Ouyang W, Nixdorf DR, Schiffman EL, Velly AM, Look JO. J Orofac Pain. 2010 Spring;24(2):139-51.

Roland Staud – FM, very little research, appears behaviorally oriented

Quote:
  • Treatment of fibromyalgia. Dussias P, Kalali AH, Staud RM. Psychiatry (Edgmont). 2010 May;7(5):15-8.
  • Negative mood mediates the effect of poor sleep on pain among chronic pain patients.
  • O’Brien EM, Waxenberg LB, Atch
Quote:
CENTER FOR SCIENTIFIC REVIEWSPECIAL EMPHASIS PANELZRG1 CFSH 802/22/2011-2/23/2011MEETING ROSTER

MEMBERS


BARANIUK, JAMES N , MD
PROFESSOR
DEPARTMENT OF MEDICINE
SCHOOL OF MEDICINE
GEORGETOWN UNIVERSITY
WASHINGTON, DC 20007

BOLES, RICHARD G , MD, PHD
DIRECTOR, CHLA CLINICAL METABOLIC AND MITOCHONDRIAL DISEASES CLINIC/SERVICES
DEPARTMENT OF PEDIATRICS
SCHOOL OF MEDICINE
CHILDREN’S HOSPITAL OF LOS ANGELES
LOS ANGELES, CA 90027

CHANG, LIN , MD
PROFESSOR
DIVISION OF DIGESTIVE DISEASES
DAVID GEFFEN SCHOOL OF MEDICINE
UNIVERSITY OF CALIFORNIA LOS ANGELES
LOS ANGELES, CA 90073

CHEN, LUCY L , MD
ASSISTANT PROFESSOR
MASSACHUSETTS GENERAL HOSPITAL
BOSTON, MA 02114

CHIALVO, DANTE R , MD
RESEARCH ASSOCIATE PROFESSOR
DEPARTMENT OF PHYSIOLOGY
SCHOOL OF MEDICINE
NORTHWESTERN UNIVERSITY
CHICAGO, IL 60611

DAVIS, MARY C , PHD
PROFESSOR
DEPARTMENT OF PSYCHOLOGY
ARIZONA STATE UNIVERSITY
TEMPE, AZ 85287

FRIEDBERG, FRED , PHD
ASSOCIATE PROFESSOR
DEPARTMENT OF PSYCHIATRY AND BEHAVIORAL SCIENCE
STONY BROOK UNIVERSITY MEDICAL CENTER
STONY BROOK , NY 11794

GERBER, NAOMI L , MD
DIRECTOR AND PROFESSOR OF REHABILITATION SCIENCE
PROFESSOR OF REHABILITATION SCIENCE
GEORGE MASON UNIVERSITY
FAIRFAX, VA 22030

GREENSPAN, JOEL D , PHD
PROFESSOR AND CHAIR
DEPARTMENT OF NEURAL AND PAIN SCIENCES
UNIVERSITY OF MARYLAND DENTAL SCHOOL
BALTIMORE, MD 21201

HANSON, MAUREEN R , PHD
LIBERTY HYDE BAILEY PROFESSOR
DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS
CORNELL UNIVERSITY
ITHACA, NY 14853

HOLLINS, MARK , PHD
PROFESSOR
DEPARTMENT OF PSYCHOLOGY
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
CHAPEL HILL, NC 27599

LERESCHE, LINDA A , SCD
PROFESSOR
DEPARTMENT OF ORAL MEDICINE
SCHOOL OF DENTISTRY
UNIVERSITY OF WASHINGTON
SEATTLE, WA 98195

MCCLURE, MYRA , PHD
PROFESSOR OF RETROVIROLOGY AND HONORARY CONSULTANT IN GU MEDICINE
HEAD OF SECTION OF INFECTIOUS DISEASES
JEFFERISS RESEARCH TRUST LABORATORIES
WRIGHT-FLEMING INSTITUTE
IMPERIAL COLLEGE LONDON
ST MARY’S CAMPUS, NORFOLK PLACE, W2 1PG, UNITED KINGDOM

MEAGHER, MARY W , PHD
PROFESSOR
DEPARTMENT OF PSYCHOLOGY
TEXAS A&M UNIVERSITY
COLLEGE STATION, TX 77843

PLESH, OCTAVIA , MD, DDS
PROFESSOR
DEPARTMENT OF RESTORATIVE DENTISTRY
SCHOOL OF DENTISTRY
UNIVERSITY OF CALIFORNIA
SAN FRANCISCO, CA 94143

SCHIFFMAN, ERIC L , DDS
DIRECTOR, TMD/OROFACIAL PAIN PROGRAM
SCHOOL OF DENTAL HEALTH
UNIVERSITY OF MINNESOTA
MINNEAPOLIS, MN 55455

STAUD, ROLAND M , MD
PROFESSOR
DEPARTMENT OF MEDICINE
UNIVERSITY OF FLORIDA SCHOOL OF MEDICINE
GAINESVILE, FL 32610

THEOHARIDES, THEOHARIS C , MD, PHD
PROFESSOR OF PHARMACOLOGY, INTERNAL MEDICINE, AND BIOCHEMISTRY
DEPARTMENT OF PHARMACOLOGY
AND EXPERIMENTAL THERAPEUTICS
TUFTS UNIVERSITY SCHOOL OF MEDICINE
BOSTON, MA 02111

YAO, HAI , PHD
ASSISTANT PROFESSOR
CLEMSON UNIVERSITY AND
MEDICAL UNIVERSITY OF SOUTH CAROLINA
CHARLESTON, SC 29425

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