There seems to be some confusion on the role of B cells in progressive MS and the link between B cells and grey matter pathology. I have made several posts on this in the past. I suggest you re-read these if you have not done so already and then I will collate all the comments and try and summarise the research findings to date in an short overview.
Multiple Sclerosis Research: Grey Matter (1) – Cortical demyelination …
05 Jun 2011
Methods: In this study specialist MS pathologists analysed global brain involvement in MS focusing on the normal-appearing white matter (NAWM) and the cortex (grey matter). Findings: (1) New and active focal inflammatory …
Multiple Sclerosis Research: Grey Matter (2) – Cortical lesions and …
05 Jun 2011
In this study the investigators were able to relate cortical or grey matter lesions and tissue loss or atrophy to cognitive impairment in patients with RRMS. “This study adds to the growing body of evidence that grey matter …
Multiple Sclerosis Research: Grey Matter (3) – Atrophy mainly affects …
05 Jun 2011
“This and other studies show that grey matter involvement is there from the start. I use this as argument for aggressive early treatment. It is better to protect the brain, particularly the grey matter, than to compensate for the …
Multiple Sclerosis Research: Grey matter (4) – Meningeal B-cell …
06 Jun 2011
The B cell that make the antibodies are found in structures called “ectopic lymphoid follicle-like structures” in the coverings of the brain and spinal cord; the covering are called the meninges. These ectopic follicles are not …
Multiple Sclerosis Research: Grey Matter (5) & B Cells: Baminercept …
07 Jun 2011
The immune system forms and maintains the ectopic B-cell follicles in the brain & spinal cord by producing a cocktail of immune messengers called cytokines. One of these messengers is called lymphotoxin; if you inhibit or …
Multiple Sclerosis Research: Grey Matter (6) and B cells …
08 Jun 2011
This study is also targeting the B cell within the central nervous system (CNS) in the hope of disrupting the ectopic B cell follicles and thereby trying to stop progressive cortical or grey matter disease progression. Rituximab is a …
Dear Professor g, are patients on Tysabri considered immunisuppressed and should they take precautions such as avoiding situations such as doctor's waiting rooms in the winter where there is a lot of viral respiratory illness?
Re: "Are patients on Tysabri considered immunosuppressed and should they take precautions such as avoiding situations such as doctor's waiting rooms in the winter where there is a lot of viral respiratory illness?"No. Apart from rare opportunistic infections of the brain or CNS (central nervous system) it looks as if Tysabri leave the immune system intact. Therefore there is no need to avoid doctors' waiting rooms etc. In the original pivotal phase 3 trial (AFFIRM STUDY) MS'ers who received Natalizumab were slightly more likely to have mild upper respiratory tract infections (common cold or sore throat) than placebo treated patients. The overall incidence of these infections was low and therefore there is no need to avoid social contact. On the contrary, MS'ers with highly active disease who go onto Natalizumab seem to regain their "joie de vivre", which may result in an increase in social contacts. In my opinion this is a good thing!
The presence of oligoclonal bands in the CSF is not MS specific, which means that B cell activation is a consequence of white/gray matter degenaration. Therefore, any effort to restrain B cells by medication is not scientifically supported and is thus unethical.
Re: "The presence of oligoclonal bands in the CSF is not MS specific, which means that B cell activation is a consequence of white/gray matter degenaration. Therefore, any effort to restrain B cells by medication is not scientifically supported and is thus unethical."Yes, we know it is not MS specific. However, in those other diseases in which we find them a large number are due to infections.
Re: "Any effort to restrain B cells by medication is not scientifically supported and is thus unethical."You should read the literature on B cells and gray matter pathology. Very interesting and some would say compelling. As an analogy you may want to dip into the rheumatoid arthritis literature and study the effects of Rituximab on B cell follicles in the joint synovium. I assume you are aware that OCBs are present in the synovial fluid of RA joints and Rituximab is now a licensed therapy for RA. So by analogy the scientific case is very strong and the phase 2 results of Rituximab and Ocrelizumab were strikingly positive. If anything it would unethical not to take anti-B cell therapies forward. Imagine telling a PPMS'er that you want to stop the ocrelizumab trial because you thought it was unethical to do? They would be horrified, particularly in view of the positive subgroup analysis of the Rituximab PPMS trial.
Re "However, in those other diseases in which we find them a large number are due to infections."Perhaps. But stroke is more common.Re "Rituximab is now a licensed therapy for RA"Licenced does not mean effective.Re "If anything it would unethical not to take anti-B cell therapies forward."Why not making more efforts on finding the infections that presumably cause MS? Why are all messing up the immune system? It seems more likely that it's all about expanding the Rituximab market.
Alemtuzumab could be seen as 'messing up' the immune system, but it's messing up a system that isn't working properly anyway. It has been shown to reduce the inflammatory process and hopefully slow down/halt progession (taking into account the future arguments about that) and is on the brink of being available. Finding the infections that may have a role in causing MS is important, but MS er's have to live in the world as it is now, and 'messing' with the immune system is available now