CFS Research Foundation: CFS/ME – XMRV Is there a connection?


Prefaced with Notes by ME agenda:

The Chief Executive of the MRC, Sir Lezek Borysiewicz, is to step down in 2010 ( Source: ME Association News page ).

Dr Tim Harrison PhD, DSc, FRCPath. is a Trustee of the CFS Research Foundation and member of the CFSRF Research Committee.

Professor Stephen T. Holgate FMedSci, MRC Clinical Professor of Immunopharmacology, University of Southampton is a member of the CFS Research Foundation’s Research Committee.

Professor Holgate chairs the MRC’s “CFS/ME Expert Panel”.

Dr Jonathon Kerr is a member of the MRC’s “CFS/ME Expert Panel”.

Dr Paul Kellam BSc PhD, Department of Infection, University College London is also a member of the CFS Research Foundation’s Research Committee and one of the project supervisors for the UCL PhD Project: Project title:

A role for XMRV in human disease  Division of Infection & Immunity, University College London: Project Supervisors: Prof G Towers; Dr P Kellam


CFSRF Newsletter

CFS/ME – XMRV Is there a connection?

It is likely that you will have heard or read about the interesting work being carried out by Dr Judy Mikovits and her team at the Whitmore Peterson Institute in Reno, Nevada to see if the retrovirus XMRV (exenotrophic murine leukaemia virus-related virus) might be associated with CFS/ME.

This research has been given tremendous coverage by the media throughout the world and while anyone suffering from CFS/ME must feel a degree of excitement we must caution restraint. A good deal more work needs to be done before too many claims can be made as to the relevance of this virus in CFS/ME.

Recently the retrovirus XMRV was found in the tumour tissue of a subset of prostate cancer patients. Both XMRV positive cancer and CFS/ME have been linked to alterations in a certain antiviral enzyme. The team in Nevada decided to carry out a study to see if this retrovirus might be associated with CFS/ME.

When the team analysed blood taken from 101 CFS/ME patients 68 (67%) tested positive to XMRV genes compared with only 8 (3.7%)out of 218 healthy controls. They stated that their results are consistent with the hypothesis that CFS/ME patients mount a specific immune response to XMRV. The have discovered a highly significant association between XMRV and CFS/ME.

The research associating XMRV with CFS/ME leaves many questions to be answered. First, it will be necessary for the study to be repeated. Over the years there have been claims for other retroviruses in other illnesses which have come to nought so it is essential that this research is found to have been concluded correctly and for the conclusions reached to be confirmed in independent studies around the world.

We have to ask the question is XMRV a cause or factor in the pathogenesis of CFS/ME oe a passenger virus in the immunosuppressed CFS patient population. Several other viruses have been linked to CFS/ME, for instance the Epstein-Barr virus, enteroviruses or herpes viruses, so we must ask what is their relationship to XMRV and the presence or absence off theses viruses.

Another question must be to ask if the virus XMRV causes CFS/ME or is it just more common in people with the illness.

In the USA the National Institutes of Health (NIH) have taken this research very seriously. They have called meetings of different departments to discuss the implications of these findings, and they and various groups throughout the world are currently setting out to determine whether this association can be confined for CFS/ME patients in Europe and other countries. They have also made a grant of $2 million to take the research further.

Dr Jonathan Kerr and Dr Judy Mikovits have been awarded $2 million from the NIH to study the disease mechanisms in CFS/ME. $1 million has been awarded to the research team in Nevada, the other $1 million has been awarded to Dr Jonathan Kerr at St George’s University of London, the scientist well known to all the supporters of the CFS Research Foundation who carried out the research which discovered 88 genes which were abnormal in CFS/ME patients but remained normal in healthy people. Dr Kerr will study CFS/ME patients to identify important genes which are turned on and off, proteins in the immune system (cytokines) and mutations in the DNA. Some of these American patients have developed Mantle Cell Lymphoma (MCL) after many years of having CFS/ME; these patients will also be included.

The CFS Research Foundation tackles some of the questions.

In spite of the large grant which Dr Jonathon Kerr has received from the NIH the Research Committee has decided that it is imperative that we know if UK and USA patients are infected with XMRV. So the Foundation is to fund a study to establish whether there is a relationship between XMRV and CFS/ME by testing samples from the UK and the USA. Dr Jonathan Kerr and Dr Kate Bishop, who is working at the national Institute for Medical Research in London, are planning to examine patients with CFS/ME and match comparison groups. They will test for the virus itself as well as for the immune responses to this virus. It is of course, vitally important to confirm or refute the finding recently published in the USA.

The Gene Work Continues

While this work is causing such excitement the work of gene expression continues. Of the 88 genes which are abnormal in the CFS/ME group but normal in the control group, Dr Kerr found that these genes could be divided into 7 subtypes. What was so interesting was that theses subtypes were associated with distinct differences in their clinical patterns and severity. Each of these subtypes had a different list of genes which were abnormal.

In a further study Dr Kerr tackled a problem which always causes great concern to CFS/ME sufferers and their families and friends. For years there has been dissension among doctors and scientists as to whether CFS/ME patients were suffering from endogenous depression. Many sufferers felt that this was holding up scientific research. Dr Kerr tested the genes of people with endogenous depression and compared them with the genes of 29 healthy blood donors. Gene levels in the endogenous depressed patients were similar to those in normal controls, but, importantly they are different from the CFS/ME patients.

Dr Kerr and his team are currently extending the previous findings by including a larger number of well-defined patients. These investigations are being conducted on a blinded basis in order to ensure that there has not been any potential bias on the technical aspects of the study. The samples have recently been collected by Dr Tim Harrison, a Reader in Molecular Virology at University College London Medical School, who visited St George’s Hospital to prepare the blinding. The samples were placed in tubes, each one coded, and then frozen. Dr Harrison will keep the code, and no one else will know it until the time set for unblinding.

You will see that this team will have made sure that their findings are accurate. This contrasts with some previous attempts carried out by other groups on a purely empirical treatment methods that have no firm scientific basis. The research being conducted at the present time by Dr Kerr and his team may well result in not only a reliable diagnostic test but also the initial steps for appropriate therapy based on firm scientific data.

The Future

The outlook for CFS/ME research has never been brighter. Increasingly, doctors and scientists are believing that this is an organic disease which need organic research. The paper from Nevada suggesting that the retrovirus XMRV might be associated with CFS/ME has caused great interest and scientists throughout the world have been attempting to repeat this study. Whether or not it is confirmed we already know that virus infection is important in CFS/ME.

We have some encouraging news from the Medical Research Council (MRC). For years people with CFS/ME, their relations, friends and some research scientists have been frustrated by the MRC’s concentration on psychiatrists when conducting research into this illness. This has now changed. The Chief Executive of the MRC, Sir Lezek Borysiewicz is anxious that CFS/ME research should go ahead in a wide field. This must be the best possible news.

The Foundation is seeking new studies of a high standard. We shall have to re-double our efforts to produce these studies and we hope we can receive some part funding from the MRC. We see the possibility of our research expanding and producing even more radical results as it has in the past. The speed at which we can go forward is up to all of us. We can now look to the future with even greater hope.

Anne Faulkner, Honorary Director