I'm a little late chiming in here (as if anybody really wants me to anyway), but every time something like this (problem with Rituxan) comes up long after I expressed my doubts and why and been chastised by others to the point of me just finally giving up and going away, I can't help
but pop back in now.
Back in October, 2005, (note the date there) I was having an MS discussion with a physician/researcher (former friend) at Vanderbilt. After reading the below, can someone tell me AGAIN why it is/was that more research money is being dumped into something that upon simple reflection does not indicate itself to be really that effective for the treatment MS? And that the risks may
not be worth it? (If someone as simple as I am can surmise that long beforehand, you can't tell me the "experts" can't do the same!?)
Here are excerpts from my email discussions with Vanderbilt (you'll once again see how outspoken I am or was, anyway. Although, you might see how I tried to "soften" up my responses to them. I finally gave up talking to them altogether.) And yes, I'm no fan of Biogen, either. No secret there, either.
(And to those who are fans of the "mabs", don't worry, I wasn't listened to and I'm sure will never be, so I pose no real threat to current MS research.)
Part of some questions proposed to me (in blue) and my answers:
Date: Monday, October 24, 2005
Is CNS apoptosis an important event in MS?
Depends. I'd say not apoptosis of the B cells, though. Not as a major factor. But yes, it's complex, but there is obvious dysfunction of cell death........macrophages, neurons..........I refer to it as "it's all in the timing".
Now having said all that, everything hinges on which pattern of MS we are referring to. And yes, I have read more and more about the PNS in connection to MS. (Remember, also, that recent ALS research on desipramine found that it has excellent CNS penetration.) Speaking, though, of the traditionally thought of PPMS as currently defined, then I'd say apoptosis is a part of it, but maybe not the "initial" event. I think PPMS is an altogether different puppy than RRMS or SPMS.
I may not be able to speak ALL the jargon off the top of my head without referring to my previous research, but there isn't much I haven't read and studied about all this. I'm no expert by any means, but maybe a fresh viewpoint might at least present some new ideas?
Then my follow-up email to them the following day, because Vandy had mentioned B cells and the PNS (peripheral nervous system):
Date: Tuesday, October 25, 2005
Ok...........I see........ they have tested rituximab on B lymphocytes in progressive MS (and basically failed). (I won't post the results I found, but I have it.) (As shown below, if somebody would have read the pharmacology of rituximab before even expending any time and money on a clinical trial of it on progressive MS, they would have seen that it was unlikely to work in the CNS.) What a waste! But..........ok!
Of course, as just mentioned above when researching the pharmacology of rituximab during lunch just now, that drug does not penetrate the CNS, it only DOES its work in the periphery: "Rituximab binding was observed on lymphoid cells in the thymus, the white pulp of the spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes." BUT, of course, notice the EXTREME coincidence, this AGAIN is being "pushed" by Biogen! I think I'm going to die laughing! God, I rest my case! (Biogen and "mabs". They'll never stop, will they?) I had NO idea I'd run across Biogen AGAIN when following up on this! I swear!!!
Ok, if you DO want to see what happens when you affect B lymphocytes in the CNS in progressive MS, again I tell ya............try desipramine. It also lowers B lymphocytes in the CNS and raises IL10 at the same time. Yes, I have mounds of research to support this claim.
I'm dying laughing. Biogen has got to be buying you guys dinner constantly! hehehe......................
That's ok.............I luv ya anyway.............even if you folks do get manipulated by them. (Yes, I know it wasn't you...........it was done in Texas, but I gotta rag on ya anyway.)
MY advice? Forget the "mabs". They are nothing but trouble and won't work in the long run anyway.
EDIT: Oh, and please remember, this is only my opinion. My opinions don't hold any weight.
I also meant to add that I hope everyone had wonderful holidays, and Happy New Year to all! All the best!