Epub ahead of print: Kap et al. B-Cell Depletion Attenuates White and Gray Matter Pathology in Marmoset Experimental Autoimmune Encephalomyelitis. J Neuropathol Exp Neurol. 2011 Oct 11.
This study investigated the effect of B-cell* depletion on central nervous system white and gray matter pathology in experimental autoimmune encephalomyelitis (EAE) in common marmosets, a relevant preclinical model of multiple sclerosis.
B cells are the cell of the immune system that make proteins called antibodies.
EAE was induced in 14 marmosets by immunization with proteins from human myelin. At 21 days after immunization, B-cell depletion was achieved by weekly intravenous injections of a human-anti-human CD20 antibody that cross-reacts with marmoset CD20. MRI showed widespread brain white matter demyelination in control marmosets that was absent in CD20 antibody-treated marmosets. High-contrast postmortem MRI showed white matter lesions in 4 of the 7 antibody-treated marmosets, but these were significantly smaller than those in controls. The same technique revealed gray matter lesions in 5 control marmosets, but none in antibody-treated marmosets. Detailed analysis confirmed that inflammation, demyelination, and axonal damage were substantially reduced in brain, spinal cord, and optic nerves of CD20 antibody-treated marmosets.
Conclusion: B-cell depletion profoundly reduced the development of both white and gray matter lesions in the marmoset CNS. These data underline the central role of B cells in CNS inflammatory-demyelinating disease.
“I am not sure about the ethics of this study as anti-CD20 treatment has already been shown to be effective in MS and is in late stage development in phase 3 in both relapsing-remitting and primary progressive MS. Do you we need to do trials in primates at this stage? What do you think?”
Trials of anti-CD20 in MS:
Ethics?MS patients are given extremely expensive drugs that manipulate the immune system WITHOUT any PROOF that the last has anything to do with the pathogenesis of HUMAN MS.There are serious moral-legal issues regarding the use of "approved" treatments for MS, not just ethics of the marmoset genocide.I repeat the conclusion of a recent research. Answers are expected: "The findings suggest that plaque formation has some basis other than destructive cell-mediated immunity directed against a myelin or oligodendrocyte antigen."from:Multiple sclerosis: distribution of inflammatory cells in newly forming lesions.Henderson AP, Barnett MH, Parratt JD, Prineas JW.http://www.ncbi.nlm.nih.gov/pubmed/20035511
Re 'answers are expected' – see if this helps multiple-sclerosis-research.blogspot.com/2011/06/article-of-interest-2-relapsing-and.html
It's not about the same research, but on the same grounds. Thanks anyway, anonymous.Still, no answers. Only a viral hypothesis that simply raises more questions.Where are the virus traces?Why does the virus prefer oligodendrocytes to neurons?How can the geography of the lesions be explained?And why oh why do we keep using DMDs since once more there is NO PROOF of a malfunctioning immune system?
I am not going to try and defend the use of primates to do this and other studies…. unethical!!!However on another point"MS patients are given …WITHOUT any PROOF that ……anything to do with the pathogenesis of HUMAN MS".Without wanting to appear rude, I disagree. If you think that immune-modulating agents do nothing in MS then I believe that you are deluding yourself. Studies have shown that immunosuppression can inhibit the formation of lesions and can inhibit relapse in MS by over 80% e.g. alemtuzumab in phase II studies.What you want an answer about the John Prineus study that suggests that oligodendrocytes have problems BEFORE the immune response arrives. This feeds into a concept that the arrival of the immune response may be secondary to the damaging event in MS. Maybe the inflammation is good? Alternatively this may be a trigger for immune cells to come in and do more damage.However you just have to look at the response to powerfull immunotherapies therapies that indicates that on balance the presence of (lymphocytic) inflammation in the brains of MSers is not good but bad. However you have to be aware that inflammation is a repair mechanism so obviously some elements of it are good.The presence of pre-active lesions in MS clearly suggest that things are going on before too much inflammation occurs. May we can ask Dr. Love to give an opinion on the and explain "Pre-active lesions"
I think it's wrong to experiment on monkeys and make them ill. In this case it seems that the research won't even produce any new information.
Just so we are clear, I also think that there are elements of MS that do not respond to those powerful immunosuppressives, but they are part of the jigsaw
Re "Studies have shown that immunosuppression can inhibit the formation of lesions and can inhibit relapse in MS by over 80% e.g. alemtuzumab in phase II studies."Long term disability is not affected by neither the number of lesions, nor the number of relapses. Do you agree?Lesions and relapses are reactions to damage. By supressing reaction you do not prevent the damage. Re "Alternatively this may be a trigger for immune cells to come in and do more damage."Please, give me PROOF that the immune system is destroying healthy cells. "May" is NOT enough.Re "However you just have to look at the response to powerfull immunotherapies therapies that indicates that on balance the presence of (lymphocytic) inflammation in the brains of MSers is not good but bad."If you stepped on a nail, would you use immunosuppresants to ease the swelling or would you try to take the nail out?
VV,I experienced serious relapses in the 2 years following diagnosis. I was fortunate to get Alemtuzumab. Five years after my first dose (of two), I have been relapse free and saw some improvement in EDSS. So I've had five years with no relapses or signs of progression. My annual MRI shows no inflammation / new lesions (many old ones have got samller or disappeared). Will I progress in the future – who knows. But I know that knocking out the inflammation with a very strong drug has given me five good years (fulltime work etc / fully mobile). What would you have done in my position – my treatment options were limited (I was still relapsing when on Rebif)?I have to put my health in the hands of the MS "experts" and follow their advice. I'm not a doctor and this disease is very, very complicated.PS I'm also getting a bit tired of your posts. You obviously think the current approach / thinking is wrong. Gut youv'e made that point, so no need to keep posting the same message. I'm looking forward to hearing Prof G's take on ECTRIMS 2011 – I'd like all users of this blog to be able to ask Prof G questions and for him to ahev time to respond – you've had your 15 minutes in the spotlight.
Dear VVLook at any picture of lesions in MS and you can see immune cells full of myelin they have just ingested they are involved in the process.Please see post by Anon above, This gives you a clear answer that your beliefs do not accomodate all current knowledge. enough said.
Re "Look at any picture of lesions in MS and you can see immune cells full of myelin they have just ingested they are involved in the process."You are talking about macrophages and you are trying to convince me that they ate healthy myelin. However:"Macrophage activity is largely an innate scavenging response to the presence of degenerate and dead myelin". Now, who dared to say that? Was it Dr.Prineas? Oh yes.
Dear anonymous, I hope you stay relapse free forever. Everybody deserves to get rid of MS.Re "I'm also getting a bit tired of your posts"Skip them. I have a few breaths left.
VV, since you reject everything that Prog G and Mouse Doctor say I can't understand why you are posting here at all. Provide a link to your own blog instead.
Re "I can't understand why you are posting here at all."I thought this blog was for patients, not just believers.
Re 'not just believers' – ok, but what's the point? As an analogy, I wouldn't waste my time reading, let alone commenting, on a homeopathy blog- even if I was furious with homeopathy for misleading a friend.
You use analgesics, anti-inflammatories and anti-biotics for a nail, not potentimmunosuppressives. If you know the cause, you can do something about it, like not treading on the nail. But if you don't then you target tangible events that are achievable.The main point of the Prineus papers were to indicate that things are going on before significant immune involvement, especially as all susceptibility genes control immuune function. Other pathologists
oops post not finished. Other pathologists have different views to prineus. Different causes have been hypothesised
Re "The main point of the Prineus papers were"His team's conclusions where crystal clear and very specific. They are talking about "dead myelin". Who killed it?Re "Other pathologists have different views to prineus."Could you provide some links to them?
Re "all susceptibility genes control immuune function"A gene does not control only one thing. What's your opinion on the following:http://www.fondazionehilarescere.org/pdf/ferlini-etal-2010-final.pdfThe authors say that these "guilty" genes take part in angiogenesis also.
A gene does not control only one thing. What's your opinion on the following:My opinion is that angiogenesis genes and CCSVI as the cause of MS is as likely as the MMR vacccine being the cause of MS.
That's more of an aforism at first sight, not an opinion on gene roles. Could be more specific as to why you regard this research wrong or irrelevant?
As an example, please read posts FRIDAY, 21 OCTOBER 2011CCSVI at ECTRIMSThis thread should be about B cells (and Marmosets). There is an interesting story from ECTRIMS. Atacicept: Targeting B cells in Multiple Sclerosis-making MS worse. Evidence for role of immune cells in the course of MS.Prof G will no doubt post on this