We wish to congratulate Dr Enlander on his new collaborative endeavour. The team put together by Dr Enlander looks impressive and we now have an opportunity to answer questions definitively. If the researches were willing to establish baseline immune profiles very much in the same manner as demonstrated by Dr Judy Mikovits we could establish unequivocally that ME is a neuroimmune disease.
Rituximab doesa lot more than deplete mature B cells. To begin, there is a molecule called IL-2 which is elevated in people examined by Dr. Mikovits who were ZMRVpositive. This molecule is a signal molecule and is pivotal in activating the immune system, and more importantly from our perspective, keeping it active. It also controls the level of certain kinds of T regulator cellcalled FoxP3. Without sufficient FoxP3 the T cells start to attack the immune system, and an over-high ratio of T Helper 17 (TH17) cells is created, as is found to be the case in auto-immune and chronic inflammatory diseases. If IL-2 (an interleukin, a type of cytokine) remains high, then the T regs response is suppressed, and an autoimmune situation will arise. Rituximab also acts as an antibody against IL-2 molecules and hence switches off or at least dampens down the activity ofthe immune system.
Rituximab could also be helping by removing TH17, a major source of autoimmune symptoms. It also reduces the level of a molecule called NF-kappaB. This is always high in people with an activated immune system and/or inpeople with activated microglia in the brain. The activated microglia are the ultimate source of neurotoxicity and mitochondrial damage. Importantly cytokine levels are maintained by NF-kappaB as is the continued activation of microglia, yet another way in which Rituximab administration could aleviate the symptoms of someone with neuroimmune activation.
Much of the molecular biology surrounding HIV has been revealed using a mouse model of the effects of a gammaretroviral infection. The virus used is a gammaretrovirus like XMRV and ZMRV and thecondition has been dubbed Murine Aids. This condition is caused by a replication defective retrovirus coding a protein, which causes B cells to expand once the retrovirus has infected the cell. This is called clonal expansion. The disease created is multisystemic likeME. Obviously if the ME retroviruses are found in B cells, as theyare in Murine Aids, then reducing the number of these B cells will aleviate symptoms. Finally, the B cells first meet the antigens (bugproteins) produced by the Murine Aids virus in the spleen, lymph nodes and the payers patches in the gut. Now, B cells tend to spend considerably more time in the compartments of the body where they first encountered anantigen than they do in the blood. In fact only about 4% of preactivated CD20 B cells are present in the blood at any given time. So looking for a ZMRV which inhabits CD20 B cells in the blood is not a very clever idea.
If base line Th17 Nf-kappa B and Tregs were established we could monitor the effects of rituximab directly and that would give the ammo for a specific licence application.
If then they are willing to use Dr Mikovits's/Dr Ruscetti's reverse transcriptase assay in its entirety, and Dr Lo's assay, we can establish the presence of ZMRVs once and for all.
Finally, there is good theoretical evidence that ZMRVs are not likely to be found in the blood at detectable copy numbers, hence a variation specifically looking for ZMRV sin gut tissue would blow the negative studies out of the water.
4 experts + onestudy = definitive answer.
Finally, for this blog we must comment on the increasing censorship endured by supporters of Dr Judy Mikovits and her research on patient forums. Wethink that hidden agendas should have no place on forums which are suppposed toserve the interests of patients rather than the intersts of individual administrators and moderators. We will endeavour to make this a safe place from which to receive unbiased information and a blog which unashamedly supports thecause of scientific research into our neurological disease and advocates for oppressed sufferers. The following is a post from Angela Kennedy a long term andhighly respected advocate.
I wanted to let people know that I have been prevented from posting on threads because I REPORTED OTHERS for blatantly breaking this forum's rules, and for them attacking other forum members, and using a campaign of intimidation and humilating tactics to silence, and called said others on what they were doing.
The moderator then said that what the person who started doing this on a particular thread, was 'fine', and has allowed it to stand.
This forum has been subject to abuse of moderator power for a long time, where moderators punish victims of abuse of forum rules, and use their power to advance their own partial positions, allowing others free rein to attack and intimidate others into silence and implied acquisance.
Free speech has been banished, and agent provocateurs of both the ideological and employed kind proliferate, spreading demoralisation and powerlessness.
Sadly forums have become one of the ways in which people who wish to advocate for this community to protect sufferers of ME/CFS against medical abuse. It is where people learn to mobilise, to discuss the issues, gather information. This forum is stopping that, and various other forums are on the way to this behaviour too.
I am speaking out because the level of abuse is blatant - I eventually recognised it for what it was. It took me a while because I actually do try and moderate my own behaviour to be reasonable. I'm no shrinking violet, and I don't have ME, so I can only imagine how dreadful this situation must be for people who are so ill - and find themselves powerless in the grip of such abuse of power and advancing of positions not in the interests of this community.
I empathise with those people on this forum - and I know there are enough of you because of discussions away from this forum- who have been intimidated and moderated into silence while others blatantly flout forum rules and intimidate others in order to advance points of view that are potentially and/or actually damaging to the interests of the ME community.
All I can hope is that this post is read before it is removed, and people will find some comfort in understanding the problem, and seek to get things changed. Whether that means leaving this forum and starting elsewhere, or having the courage to tell Cort and friends where they are going wrong has to be up to individuals.
This community has been under siege for too long. Friendly fire has ALWAYS been a problem, and the level of friendly fire has intensified with the advent of Mikovits's research. Sadly this is far more serious an issue than silly spats on a forum.
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