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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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I'm pretty sure Dr Edwards said he doesn't see ocrelizumab in the future of ME/CFS and that there are better b cell depleting agents in the pipeline.I think that`s the gist of it Jaybee00, maybe @Jonathan Edwards knows if there`s anything more.
I'm pretty sure Dr Edwards said he doesn't see ocrelizumab in the future of ME/CFS and that there are better b cell depleting agents in the pipeline.
Yeah true, but which agents? I see few reasons not to do a trial, if there are no other obvious choices about.
Supposedly we need agents who reach lymph nodes, bone marrow?, spleen.
Why does rtx not work here very well? I have no ida, but iv`e read that to be the case, and i lack understanding of why.
Ocrelizumab was mark 2, even the same company is on about mark 4 or mark 5 now. There is one particular antibody in development that has a more powerful B cell killing effector mechanism. I suspect they are all humanised (or human) now. Which would be the next one to be tried out will be a matter of practicalities and politics.
Thanks prof
Interesting insight!
I guess it makes sense to wait until the phase 3-trials are done before another b-cell depletion study is carried out. Another one than rtx, that is
I know it's an old thread, but if I may ask: Why is it important how potent the MAB is, given that Rituximab at doses used in the Norwegian trials usually destroys all B cells and they are 0 in the blood after just a few days?
Couldn't a more potent antibody just destroy them a few days faster? Given the timeframe for response to treatment (2-6 months minimum), this shouldn't matter much, right?
B cells in the blood are not the only ones and probably not the important ones. They may be 1% of the total. Most B cells are in lymph nodes and spleen where they hide in clusters protected by nurse cells carrying complement inhibitors. That makes them harder to kill. We do not know how many B cells in lymph nodes are killed by any of these drugs but it is almost certainly not all, at least in many cases. So there is room for more powerful versions.
Is it safe to assume, however, that drugs that are better at killing B-cells in lymph nodes and the spleen would be significantly more dangerous than Rituximab?
B cells in the blood are not the only ones and probably not the important ones. They may be 1% of the total. Most B cells are in lymph nodes and spleen where they hide in clusters protected by nurse cells carrying complement inhibitors. That makes them harder to kill. We do not know how many B cells in lymph nodes are killed by any of these drugs but it is almost certainly not all, at least in many cases. So there is room for more powerful versions.
Also, if it's impossible to tell how many of these "hidden" B-cells are being destroyed, how are drug companies going to know if the drugs they're developing are actually going to be better at targeting them?