Journal of IiME Volume 6 Issue 1 (June 2012) “In the end I think we have to find the cause behind the disease, or else no one will believe us. If we are right, which I think we are, we will make it. In a few years I think the scientific community will have the answer”, said Fluge responding to some of the doubting critics. It is important to acknowledge, like Fluge and Mella themselves have repeatedly said, that there is need for bigger studies before concluding on Rituximab and ME/CFS. And this study, like every innovative scientific study, also needs to be subject for criticism and disagreements to make headway for what we all want in the end – the truth. So why did I mention Jonathan Edwards? I did because he has been here, right where ME/CFS is now with Rituximab, just with a different disease. And Jonathan Edwards won the dispute. No one ridicules his ideas anymore. In the 1990s Edwards, together with another British scientist, Geraldine Cambridge, came up with a theory about possible B-cell involvement in rheumatoid arthritis (RA). They met a cold shoulder from the rest of the research community. The importance of T-cells was then the only accepted theory in RA, and therefore most in the medical community automatically thought that the theory of Edwards and Cambridge were not worth pursuing. But Edwards and his colleagues pursued their idea despite the resistance, starting off with a small pilot study on Rituximab in five RA patients. "When the patients' B cells disappeared, so did most of their arthritis," Edwards told New Scientist in 2001. Three of the five patients remained well for a longer period, while symptoms of the disease came back in two patients once their B cells returned. After years of unproductive battling trying to get this groundbreaking idea of the importance of Bcells in RA acknowledged in the medical community, Edwards talked to the press, and the story made headlines. Something which of course made some of his critics even more critical, but it worked. Finally they got funding for a big study on Rituximab in RA, and in 2004 the results were published in the prestigious New England Journal of Medicine. The result? Rituximab turned out to be a superior treatment in the study, and suddenly B-cells were on everybody’s lips. An article on the history of RA and Rituximab in The National in 2009 ends by mentioning Mella and Fluge’s pilot study on Rituximab in three Invest in ME (Charity Nr. 1114035) ME/CFS patients, which then had just been published: “With so few patients, it’s hardly definitive proof of a cure. Yet it is just the situation Prof Edwards and Dr Cambridge found themselves in a decade ago. CFS sufferers must be hoping medical researchers are not about to repeat history by rejecting these intriguing findings out of hand – despite not having any better ideas themselves.” Against the odds, Jonathan Edwards and his colleagues turned the whole field of RA around through pure persistence. He definitely knows that paradigm shifts do happen in medicine. No stranger from controversy, maybe Edwards gets that old feeling back reading the PLoS ONE study from Mella and Fluge, tempting him to have his say in public. Maybe he knows that the Norwegian scientists are in for a hell of a ride. And maybe, just maybe, he wants them to win too. After the article was written Jørgen Jelstad also conducted a short Q&A session with Dr Fluge – Q & A with Olav Mella and Øystein Fluge 1. What is your current hypothesis for why Rituximab works? Our working hypothesis has been, and still is, that ME/CFS might be an autoimmune disease. Maybe it should at this stage be called a disease of immune dysregulation, and inflammation probably also is a factor. So right now our hypothesis is that ME/CFS might be an autoimmune/autoinflammatory condition. 2. Why do most of the responding patients relapse after experiencing several months of improvement? We do not yet know. But we see that with maintenance treatment some patients have a continuous major improvement lasting for months, even years. Another interesting observation is that some patients have a worsening of ME-symptoms right after the www.investinme.org Page 17 of 108
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