CrowdSpeak & ResearchSpeak: EBV and HSCT

Could HSCT be working via EBV?  #MSResearch #MSBlog #CrowdSpeak #CrowdacureMS

"Yesterday the Mouse Doctor asked me how do we reconcile the results of bone marrow transplantation (BMT) and/or HSCT with the EBV hypothesis of MS? The simple answer is I don't know. However, all high-efficacy DMTs have effects on B-cells including BMT/HSCT. This form of therapy may therefore be working via depleting B cells; not too dissimilar to what occurs with cladribine, alemtuzumab, mitoxantrone, cyclophosphamide and anti-CD20 therapy (rituximab, ocrelizumab, ofatumumab)."

"The case studies below show that BMT can actually eliminate EBV from the body or at least a strain of EBV. I am aware of a similar unpublished case with MS who was found to be EBV negative 5 years after having received alemtuzumab treatment for very active MS. This is why the very promising results of BMT/HSCT trials are not incompatible with the EBV causation hypothesis. What I can say is that until we do the trial of targeting EBV with a specific anti-EBV drug we won't be able to sort out this issue. Can you imagine what would happen to the field of MS if a small molecule anti-EBV drug proved to as effective as HSCT? That is what I refer to as a black swan.This is another reason for us to get our Charcot 2 project off the ground as soon as possible. Our fund raising is going very well with close to 200 donors already. For those of you who have donated already, thank you it is much appreciated. Despite early reservations I am now thrilled to have launched this initiative; it is taking PPI to another level at least in the UK. Once we have reached our target we plan to get the lab work completed as soon as possible. We will also display the results to you in real time and engage you with the design of the next study and the associated grant application. This is what we call citizen-informed science."

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Gratama et al. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8693-6.

Background: Wild-type strains of Epstein-Barr virus (EBV) can be distinguished on the basis of variations in the molecular weight of virus-encoded, growth transformation-associated proteins. 

Case studies: This approach was used to study the persistence of EBV in two seropositive recipients of allogeneic bone marrow transplants. The first patient received marrow from her EBV-seronegative brother, became EBV seronegative after grafting, and remained so for greater than 1200 days. Subsequently, she became infected with a new EBV strain that differed from her pretransplant strain but was indistinguishable from the virus isolated from her husband. The second patient received marrow from his EBV-seropositive brother. This patient showed only a transient decrease in IgG antibodies to EBV capsid antigen. His pretransplant strain differed from the virus of his donor. On days 252 and 915 after transplantation, lymphoblastoid cell lines were grown from the peripheral blood of the patient and were found to carry exclusively the virus of the donor. 

Conclusions: These results suggest that the latently EBV-infected host cells reside in a cellular compartment that can be destroyed by graft-versus-host reactivity, irradiation, or cytotoxic drugs. Hemopoietic tissue is the most likely candidate.

CoI: Team G will be recipients of a grant from Crowdacure to perform this research

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