Wednesday, 1 June 2011

Abstract for the MS Frontiers Meeting


I am giving a debate at the MS Frontiers meeting taking place 23-24 June 2011 at Sofitel , Heathrow. The following is my abstract.

"Multiple Sclerosis is caused by Epstein Barr virus"

"Is there sufficient data to support EBV as being the cause of MS? Clearly, further research is required to disprove the hypothesis. Is it premature and irresponsible to make claims of causation? People with MS feel that the issues around EBV are very complex and difficult to interpret, and that there are too many unanswered questions to support the claim that “EBV is the possible cause of MS”. It is clear that MS is a complex disease, i.e. it results from an interaction between genes and the environment. The majority of the genetic susceptibility to MS is linked to specific MHC haplotypes. Migration studies indicate that exposure to an environmental factor(s) in early adolescence or childhood causes or contributes to the cause of MS. The incidence of MS is increasing. In some populations the female:male sex ratio of people affected with MS has gradually been increasing. Smoking, levels of sunlight exposure (latitude), vitamin D metabolism and season of birth are other factors that are associated with MS risk. If EBV causes MS all these factors have to be explained. In contrast the evidence for other causative factors is less well established. The following are some of the reasons that support the claim that EBV causes MS:
  1. Virtually all subjects with MS (>99%) are infected with EBV compared to only ~90% of control subjects. 
  2. MS is very rare in subjects who are not infected with EBV. 
  3. People with MS have an increased tendency for spontaneous in-vitro lymphocyte transformation. 
  4. People who have had symptomatic EBV infection or glandular fever have a higher risk of developing MS compared to people who have not had glandular fever (relative risk ~2.4). 
  5. People with higher levels of antibodies to EBV have a higher risk of developing MS compared to subjects with low antibody levels. 
  6. A unusual cluster of MS in children attending a school in rural Denmark occurred shortly after an outbreak of glandular fever. 
  7. A undefined proportion of antibodies in the spinal fluid of subjects with MS recognise EBV-specific. 
  8. Autoimmune MBP-specific T cells in the circulation of subjects with MS, which are capable of orchestrating an attack on myelin producing cells, also recognise EBV antigens. 
  9. Subjects with MS have a higher number of circulating T cells that recognise EBV than controls subjects. 
  10. There is evidence that during MS relapses EBV is actively replicating compared to period of remission MS, suggesting that MS relapses or disease activity may be triggered by peripheral EBV replication. 
  11. Drugs that target B-cells are effective in MS. 
Despite this evidence EBV does not fulfil Koch’s postulates, but does fulfill many contemporary criteria for causation. Causation, however, is a complex science and more extensive and definitive data is required to convince the wider community that EBV is the pivotal factor in the complex causal pathway that ultimately leads to the development of MS. To establish EBV as the cause of MS all aspects of the epidemiology of MS and specific clinical observations will need to be explained or at least be concordant with the hypothesis; for example response to specific classes of disease-modifying therapies. Establishing the causal link between EBV infection and MS will provide several new therapeutic and preventative strategies for people and their families living with the disease."

5 comments:

  1. You don't need to convince me. I've never smoked, had lots of outdoor hobbies (Vit D) as a child, but a bad case of GF as a teenager. Guy at work had GF at 25 and two years later was dx with MS. Recent question on a US MS website asked 'what do you think caused your MS'. Surprising how many of the responders mentioned a bad case on Mono (GF) as a teenager.

    A couple of years ago I saw some research by a Dr Aloissi (?sp) - Italian researcher. It looked as if they had found EBV infected cells in the MS brain - but all seems to have gone quiet! (assuming couldn't be replicated)

    It would be good to pin this down in the next 3-5 years i.e. definitive answer. What other causes are being presented at the conference?

    ReplyDelete
  2. Michael J. Fox was told on the Oprah Winfrey show by some guy called Dr. Oz that Parkinson's Disease should be curable within the next 8 to 9 years (see here: http://www.youtube.com/watch?v=lDFJOzu9SyM).

    It'd be nice if someone could be as equally confident about curing MS.

    ReplyDelete
  3. Prof, what are your thoughts on MP Pender's hypothesis re EBV and MS?

    ReplyDelete
  4. Re "Pender's hypothesis": nice in theory, but there is no evidence to support auto-reactive B cells being immortalised in MS. The EBV experts have dismissed this as not being possible; this usually means that it has not been investigated properly. In short we need to remain open to the possibility.

    ReplyDelete
  5. Sounds interesting - hopefully you will blog about the contributions at the conference - you are in danger of becoming a full time blogger:-)

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.