Targeting EBV infected cells using immunotherapy. Is this the future of MS treatment? #MSBlog #MSResearch
“If you have been following this blog you will know that I am a firm believer that EBV causes MS. I say believer because when you apply Bradford-Hill’s criteria for causation we are not quite there yet. We need experimental proof that EBV causes MS and we need to understand how EBV interacts with the human biology to trigger or drive MS. EBV also has the explain everything we know about the epidemiology of the disease; for example the worldwide distribution of the disease, sex ratio, month of birth effect, parent-of-origin effect, changing incidence of the disease, treatment response to various classes of drugs, etc.”
“I say EBV trigger or EBV driver because we don’t know if EBV acts early in the causal pathway as a hit and run agent that triggers MS and then MS runs amok without the need for an ongoing role of the virus. In comparison the driver hypothesis is that EBV drives the disease and is needed throughout the course of the disease. If the latter is the case then we can target EBV with drugs or other anti-viral strategies to treat MS. This is what we are trying to achieve with the Charcot Project; the drugs we are choosing all target EBV or downstream events triggered by EBV.”
“The case study below from Michael Pender’s group supports an ongoing role for EBV in MS. They took CD8+ T cells from a SPMSer and supercharged them in the lab. These CD8+ T cells (a type of white blood cell) are akin to heat-seeking killer missiles that are targeted to EBV-infected cells within the body; they find these cells and kill them releasing proteins that literally punch holes in infected cells. The treatment was safe without any adverse events and remarkably the MSer improved. One swallow does not make a summer and this study will need to be repeated on a larger number of MSers. If this treatment is found to be safe it needs to be tested in a double-blind placebo-controlled study. I would suggest that instead of a placebo that an active control is used, for example CD8+ T cells directed at non-EBV viral proteins. The actve control is to make sure that the treatment response is not non-specific, i.e. simply due to something related to the infusion of activated T-cells.”
“Why is this research so important? Simply because it is challenging the current autoimmune dogma about MS that has a lot of holes in it. It is also part of the experimental evidence we need to prove that EBV is the cause of MS. Can you imagine what this would do to the field of MS? What it will do to the treatment of MS? What it will do the market of MS DMTs? This could be the black swan moment I have been waiting for. In my mind it is not a question about whether a black swan will land, but when.”
“For those of you confused by this talk of black swans should read my earlier posts on the subject.”
|Who said a black swan has to look and feel like a feathered bird?
“I would like to congratulate and thank Michael Pender and his colleagues for pursuing this work. You are brave people and your pioneering attitude and commitment to this field of work is much admired and appreciated. Please keep up the good work.”
Pender et al. Epstein–Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis Mult Sclerosis Journal Epub
Defective control of Epstein–Barr virus (EBV) infection by cytotoxic CD8+ T cells might predispose to multiple sclerosis (MS) by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. We have treated a patient with secondary progressive MS with in vitro-expanded autologous EBV-specific CD8+ T cells directed against viral latent proteins. This adoptive immunotherapy had no adverse effects and the patient showed clinical improvement with reduced disease activity on magnetic resonance imaging and decreased intrathecal immunoglobulin production. This is the first report of the use of EBV-specific adoptive immunotherapy to treat MS or any other autoimmune disease.