Dr Gow Gene Disrupter! MEA funded

[Guest guest]

This is the Docter who have been funded by the MEAssociation

(www.meassociation.org.uk) for 5 years research total raised by

members and legacies is £79.000 the money is now running out please

donate any amount however small... even a few dollars would help...

thanks

Angie

MEA Director

Gene Research: A Scientific 'Signature' for ME/CFS?

The work by Dr Gow and colleagues (University Department of

Neurology, University of Glasgow), to whom MERGE has contributed

interim funding for the verification of potentially important genes,

is one of a number of ongoing research projects seeking

a 'biomarker' for the illness ME/CFS using novel microarray

technology. In this experimental technique, a sample of blood or

tissue is taken, applied to a glass slide (microarray) containing

more than 20,000 gene identifiers, and examined to determine which

genes in the sample are being expressed.

As has been reported in a series of articles — in the Scotsman, the

Evening Times, and on the BBC — the pilot data obtained by Dr Gow's

team have suggested alterations to genes controlling the metabolism

of prostaglandin and those regulation-specific immune cells. This is

interesting work which deserves to be supported into its mature

phase when a specific " gene signature " for particular proteins may

be revealed.

Contemporaneously, microarray investigations using samples from

ME/CFS patients are being undertaken by other research groups. One

team, led by Dr Kerr at St 's Campus Imperial College

London, supported by the CFSRF, is to publish a paper containing

early results in the Journal of Clinical Pathology (J Clin Path

2005; 58:860-863) in August 2005: a recent article on this work in

New Scientist (see Chronic fatigue is not all in the mind) reports

that using real-time PCR 15 of the genes were up to four times as

active in people with ME/CFS, while one gene was less active, and

that Dr Kerr is at present repeating the study in 1000 CFS patients

and healthy controls, this time looking at 47,000 gene products.

Another group, led by Suzanne Vernon of the Centers for Disease

Control and Prevention's molecular epidemiology programme in Atlanta

is investigating gene expression profiles in the large Wichita

clinical data set (see From Scepticism to Science). The preliminary

findings of these groups suggest dysregulation of genes involved in

immune pathways, supporting the many reports in the literature of

immune dysregulation in the pathogenesis of ME/CFS.

These developments are welcome: few areas of biomedical research

into ME/CFS can boast more than two separate research groups

simultaneously engaged on a common quest. It is likely to be a long

search, however. Experience from the use of genome-wide scanning

technologies for cancer screening has shown that discovery and

validation of biomarkers requires multiple phases of research. In a

lucid commentary, Sullivan Pepe et al. (2001) identified issues to

be addressed for the design of biomarker studies, and outlined a

five-phase structure for investigation — from phase 1 pre-clinical

exploratory studies to identify leads for potentially useful

biomarkers and prioritise identified leads, through phase 2

involving the development of a clinical biomarker assay and

assessment of its ability to distinguish patients and controls, to

subsequent phases of increasingly stringent validation involving

longitudinal, prospective, and large, expensive control studies. The

publicly available preliminary information on the status of genome-

wide scanning technologies in ME/CFS suggests that most work is

presently in or around the phase 1 stage, and that much progress in

bioassay development and validation studies will be required before

a valid 'gene signature' can be unveiled.

Of course, the same problems that confront all researchers in ME/CFS

also apply to research groups using microarray technology. One is

that 'diagnosis' of the illness is most often based on a ragbag of

common non-specific symptoms, resulting in a diverse group of

patients. As et al. (2005) have pointed out in an excellent

recent review, " Subgrouping is the key to understanding how CFS

begins, how it is maintained… and in the best case, how it can be

prevented, treated and cured. " It is unlikely, therefore, that a

single biomarker or cluster will be found able to detect all cases

as currently defined, although microarray technology does have the

potential to make diagnosis more precise in the long term. Another

problem is that obtaining and maintaining funding haunts the efforts

of all biomedical researchers in ME/CFS, and it is particularly

acute in these gene biomarker studies which will require million of

dollars to come to a definitive conclusion. At MERGE, we echo the

comment of Fergusson MSP in the Parliamentary members' business

debate (Thursday 9 June 2005; motion S2M-2852) on the subject of a

cure for myalgic encephalomyelitis, that it is entirely unacceptable

that major funding bodies seem prepared to see novel gene research

grind to a halt — particularly when large traunches of money have

been allocated to research on non-curative psychosocial strategies

designed to 'manage' symptoms.

Illnesses are most easily accepted when they have a specific

clinical or scientific 'signature'— a biochemical test, a cluster of

specific symptoms or signs, etc. — that confers legitimacy in the

eyes of healthcare professionals. Until then, patients are in a no-

man's land between the living and the well, subject to a variety of

quasi-therapeutic interventions and the ministrations of charlatans.

ME/CFS has been called the " disease of a thousand names " , but it has

also been the disease of a thousand false dawns and a thousand

broken promises. Yet, the discovery of a clinical or

scientific 'signature' for ME/CFS, indicative of the physical

terrain, would transform this situation at a single sharp stroke. In

the longer term, work using genome-wide scanning technologies has

the potential to reveal such a 'signature': to quote Steinau et al.

(2004), " Biomarkers characteristic of CFS could contribute to

precision in case ascertainment, identify heterogeneity in the CFS

population to clarify contributing pathways to disease, suggest

novel therapeutic targets, and provide indicators of disease

progression and prognosis. "

Many people have made contact about supporting Dr Gow's work through

MERGE, and we are delighted to accept contributions specifically

targeted at this study. Potential contributors should make clear in

their letters and e-mails that their donation is to be spent on

the 'University of Glasgow Gene Expression' project.

References

LA, et al. Chronic Fatigue Syndrome: The Need for Subtypes.

Neuropsychology Review 2005; 15(1):29-58.

Sullivan Pepe M, et al. Phases of biomarker development for early

detection of cancer. J Natl Cancer Inst 2001; 93:1054-61.

Steinau M, et al. Differential-display PCR of peripheral blood for

biomarker discovery in chronic fatigue syndrome. J Mol Med 2004; 82

(11):750-5.

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