In spite of the CMO’s intervention there has been little response from scientists. This must be in part because the MRC would seem to be mainly interested in the views of psychiatrists in spite of the fact that evidence is mounting showing the organic nature of the disease.
In the U.K. the CFS Research Foundation has been meeting the challenge of CFS since it was established in 1992 and officially launched in 1993. Because of the poor quality of the little research which was being carried out at the time, it determined to fund only that research deemed to be of the highest scientific and ethical standards and to this end it established a research committee of scientists who were pre-eminent in their fields. This has paid dividends and the Foundation now has a respectable portfolio of papers published in scientific journals following research funded by the Foundation into different aspects of the illness.
Dr Russell Lane took muscle biopsies from CFS/ME patients at his neurological clinic in London. He carefully eliminated those who had any form of psychological problem. The remaining patients showed increased lactic acid production on exercise making the blood more acidic and causing muscle pain and fatigue; this group seemed to be largely distinct from the group with psychological problems. Professor Len Archard and his colleagues, using sophisticated scientific techniques, found evidence of enterovirus nucleic acid (RNA) in the muscle of some patients. Furthermore, they confirmed this using a different technique and showed that the virus was related to the enterovirus Coxsackie B3. [1] In a later collaboration with Dr Lane they showed that there is an association between detecting the viral RNA and an abnormal result on the exercise test.
There was an entirely independent study in Glasgow in which enterovirus RNA was detected in the blood of locally recruited CFS/ME patients with similar results. The results were published in the Journal of General Virology. [2]
Using a slightly different approach Dr Jonathan Kerr of Imperial College London, followed up a group of patients shown by laboratory tests to have been infected with another common virus, the parvovirus B19. A number complained of continuing fatigue and 13% of them had the symptoms of CFS/ME. He treated three of these patients with large doses of immune globulin (IgG) and all three recovered, the virus disappeared and the immune system returned to normal. [3]
The Foundation also funded a project to look for evidence of some human genes becoming more active in patients with CFS /ME. The work was done by Dr R Powell, firstly with Professor J Almond at Reading and then with Professor S Holgate in Southampton, where the patients and control subjects were recruited. White blood cells from about half a dozen patients and a few matched normal subjects yielded evidence that there were several genes which had become more active in the patients. [4]
In the light of this research, together with current developments human genetics and the rapid advances in sophisticated scientific technology, it was decided that it was possible to study the basis of the disease by examining gene expression in patients. We already had evidence from Dr Powell’s study that several of the patients’ genes involved in regulating immune responses might be activated, thus producing the general symptoms of CFS/ME.
The Research Committee decided that it was vital that these studies should be followed by a multi-centre study.
The Foundation is funding Dr Jonathan Kerr and colleagues, now at St George’s University of London, to elucidate the gene expression signature of CFS, and also to discover protein biomarkers in the serum of patients which can be used to develop a diagnostic test. The group has studied peripheral white blood cells from approximately 55 CFS patients and 75 normal controls using a microarray representing the entire human genome, with confirmation using Taqman real-time PCR. This approach has identified 88 human genes which are differentially expressed in CFS. These genes can be used to identify subtype of CFS, which have distinct profiles of clinical symptoms and levels of severity [6]. These 88 genes include the original 16 genes which were identified during a pilot study [5] Future work will confirm the specificity of this signature to CFS using more cases, normal persons and a range of disease controls.
The Foundation now wishes to extend its research to include studies in various aspects of the disease using immunological, virological and genomic approaches. Grants have been awarded over the years ranging from £5,000 over three years to the present study which was awarded a grant of £1.1 million over six years.
References
[1] Lane R.J.M, Soteriou B.A., Zhang H., Archard L.C. Enterovirus related
metabolic myopathy: a post viral fatigue syndrome. J. Neurol Neurosurg
Psychiatry 2003; 1382-1386. [PubMed].
[2] Galbraith D.N., Nairn C. and Clements G.B. Evidence for enteroviral persistence in humans. Journal of General Virology 1997; 78:307-312. [PubMed].
[3] Kerr J.R., Cunniffe V.S., Kelleher P., Bernstein R.M., and Bruce I.N. Successful Intravenous Immunoglobulin Therapy in 3 Cases of Parvovirus B19-Associated Chronic Fatigue Syndrome. Clinical Infectious Diseases 2003; 36:e100-6. [PubMed].
[4] Powell R., Ren J., Lewith G., Barclay W., Holgate S., and Almond J. Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients. Clin Exp Allergy 2003; 33:1450-1456. [PubMed].
[5] Kaushik N, Fear D, Richards SC, McDermott CR, Nuwaysir EF, Kellam P, Harrison TJ, Wilkinson RJ, Tyrrell DA, Holgate ST, Kerr JR. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J Clin Pathol. 2005; 58:826-832. [PubMed].
[6] Kerr JR, Petty R, Burke B, et al. Differentially expressed genes in Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) patients reveal seven subtypes with distinct clinical phenotypes. J Infect Dis 2007 (in press).