This Is MS Multiple Sclerosis Community: Knowledge & Support

Antibodies to Myelin Don't Signal MS

By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine
January 24, 2007


Basel, Switzerland, Jan. 24 -- Contrary to a previous report, the presence in the blood of two types of antibodies to myelin is not diagnostic of multiple sclerosis, investigators here reported.

Nor does the presence of the antibodies indicate a risk of progression to clinically definite MS, found Jens Kuhle, M.D., of University Hospital here, along with European and Canadian investigators.


Although other investigators have found that the patients with serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein were at increased risk for MS, Dr. Kuhle and colleagues could find no such link, they reported in the Jan. 25 issue of the New England Journal of Medicine.


In a study of 462 patients with a first clinical event suggestive of MS and at least two silent brain lesions on MRI, there was no association between serum levels of either of two antimyelin antibody types and risk of progression to clinically definite MS.


"Our results strongly suggest that antimyelin antibodies have no role in the diagnosis of multiple sclerosis or in the identification of patients at high risk for the development of clinically definite disease," the investigators wrote. "Alternatively, there may be a role for such antibodies, but we may need more sophisticated methods to detect them."


The investigators used serum samples from the 462 patients enrolled in the BENEFIT study, a randomized double-blind, placebo-controlled, phase III trial evaluating Betaseron (interferon beta-1b) at a dose of 250 μg subcutaneously every other day in patients with a first clinical episode suggestive of MS, and at least two clinically silent lesions detect on MRI scans of the brain.


They measured serum anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein at baseline by Western blot analysis, and compared the results with the time and rate of progression to clinically definite multiple sclerosis, or to a diagnosis of multiple sclerosis as defined by an international panel (the McDonald criteria).


The patients had regular visits for the assessment of neurologic impairment and for MRI before treatment and at months three, six, nine, 12, 18, and 24.


They used chi square analysis and the Kruskal-Wallis test to compare the baseline characteristics of the patients in the placebo and treatment groups according to antibody status.


They used Kaplan-Meier analysis to calculate cumulative risk of progression to clinically definite multiple sclerosis, or multiple sclerosis as defined by the McDonald criteria), and created Cox proportional-hazards models adjusted for potential confounding variables to assess whether antibody status predicted the development of MS.


They controlled for age, sex, use of corticosteroid treatment for the first event, the effect of treatment with Betaseron, multifocal or monofocal disease presentation, and the number of gadolinium-enhancing lesions on T1-weighted MRI scans and the number of hyperintense lesions on T2-weighted scans.


During the two-year study, 150 patients (32%) were diagnosed with clinically definite multiple sclerosis, and 331 (72%) were diagnosed with MS according to the McDonald criteria.


The authors found that "there was no increase in the risk of clinically definite multiple sclerosis or of multiple sclerosis according to the McDonald criteria among patients who were positive for anti-myelin oligodendrocyte glycoprotein antibodies, anti-myelin basic protein antibodies, or both," the authors wrote.


"This was true for both IgM and IgG antibodies not only in the total study population but also in all subgroups analyzed: patients receiving placebo or interferon beta-1b, patients with positive cerebrospinal fluid findings, patients who had received corticosteroid treatment, and patients with shorter or longer intervals between the initial clinical event and blood collection."


"Finally, we were unable to confirm the previously reported association between the number of lesions seen on gadolinium-enhanced MRI brain scans and the anti-myelin oligodendrocyte glycoprotein or anti-myelin basic protein antibody status," they added.


They noted that time of blood sample collection -- for example, within a few days of the first manifestation of clinical disease and before corticosteroids -- could have had an influence on the results.


They also acknowledged that the follow-up in the study, which was limited to two years, may have been too short to detect a positive correlation between the antibodies and MS.


"However, in view of the number of patients in whom clinically definite multiple sclerosis or multiple sclerosis according to the Mc-Donald criteria was diagnosed during the two-year follow-up period, a major change in the results with longer follow-up would be highly improbable, " they wrote.

The study was supported in part by Schering AG, which sponsored the BENEFIT study, and by a grant from the Swiss Multiple Sclerosis Society.

So basically there is no evidence that we have "auto-immune" reactions to myelin?? Or have I misunderstood?

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

I'd be interested to hear what others think but to me it seems to mean that despite the presences of myelin antibodies, the presence of myelin antibodies doesn't predict whether someone has or is going to get MS.
Bob

Yes, I think you're right and that I've read before that you can have MS with no myelin-reactive antibodies and you can have myelin-reactive antibodies and not get MS. It seems the whole focus on myelin auto-reactivity isn't the answer.

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

For those of you who are aware of my ongoing skepicism re: MS not being an autoimmune disease, I find this particularly interesting. If this is really putting a dent in the autoimmune theory, we can be assured Jens Kuhle, M.D has now been spirited away with the panel of docs whose postion paper on Tysabri stated it was only effective for about 9 months!!

Just kidding here folks! Just read about a doc who used an antiviral med for his Chronic Fatique Syndrome patients in the hopes it might decrease their level of fatique. Began to realize patients were regaining their total health! There is now a drug trial with this drug and CFS patients. What I find interesting? If you read the theory behind CFS you would think you were reading about MS.

Thanks so much for this article. I will save it in my "MS file" as a keeper.

Well, it does rather question the validity of claims that we are all reacting to our own myelin. Clearly whether one reacts or not to myelin is irrelevant to whether one gets MS or not. Doesn't sound like tovaxin is going to work then. Booo.

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

Gibble--don't be too discouraged. If my theory is correct---that MS is not just "one" disease--Tovaxin might be very effective for some.

I see you guys are enjoying running with this one but if this topic has ANYTHING to do with whether or not MS is autoimmune driven, please share your reasoning
Bob

Well, the above research strongly implies that reactivity to myelin is irrelevant. This does seem to scupper the autoimmunity theory in as far as it relates to myelin which is of course what the researchers have been implying for the last several decades. Not that this will materially alter the focus of research for the vast majority of pharmaceutical companies since mucking around with our immune systems seems to produce fat profits for them and increasing disability and possibly death for the rest of us.

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

Hello everyone,

Chris55, I'd love to read some more about that Dr trialling anti-viral drugs to treat CFS. D'you have any links or more information? I've been taking amantadine for about five years now: it was prescribed for fatigue and has helped me enormously... before I started, a single 20 minute conversation could wipe me out for two days, now I have carers in for 16 hours a day, plus long chats with friends, and I feel as if I could talk forever! (unfortunately, amantadine doesn't actually help me to make any more sense than I did before).
If I remember correctly, amantadine was originally an anti-viral flu prevention drug which, when given to MS patients to help protect against the flu, was noted to reduce fatigue in about 30 per cent of cases.

I can't help thinking that there are indeed several causes to this disease. If a viral infection, a bacterium, or even physical injury, (all of which have been postulated as potential "triggers"), expose the "right" sequence of peptides to the immune system, then the phenomenon of epitope spreading can occur, (a personal favourite of mine), which would Prime the immune system against self tissue.

I'm not sure if that makes me an "auto-immune" believer or not. I suppose I'm thinking that autoimmunity does occur, but it must be in conjunction with something else, and can be triggered by a cascade of different events; this is why different treatment regimens work for different people... the original cause of ES is different. ...it's not a new idea, but it still appeals to me. I don't understand why the researchers have assumed a 2-year latency period is long enough to support their theory: who knows how long we can have antibodies and be asymptomatic, after all, lesion load seems to not reflect in EDSS?
.
What does everyone think?

Dom.

Dom--the article is actually on this site--can't remember the subject. The criteria for CFS I just looked up on my own. Here's the article:

A Herpes Drug May Make Energy Soar for Chronic Fatigue Syndrome Patients
by Editor
ImmuneSupport.com

05-25-2006
A drug normally used to treat herpes infections has produced a dramatic improvement in patients suffering from Chronic Fatigue Syndrome (CFS). Patients that had formerly been house-bound report being restored to normal life activities. CFS affects about 1 million patients in the United States, and about 240,000 in Britain. There is no cure for CFS, only ways to manage the condition.
The London Daily Mail newspaper reported the study results, which were delivered at a scientific conference earlier this month by Professor Jose Montoya, M.D., an infectious disease researcher and Associate Professor at Stanford University. The study took place in California, and involved 12 CFS patients who were given the drug valganciclovir, which targets the human herpes virus (HHV-6). Nine of the 12 patients reported a great improvement in their condition. The professor’s findings were reported at a conference on the HHV-6 virus held in Barcelona earlier this month.
Donna Flowers, a onetime champion figure skater now aged 50 and working as a physiotherapist, was quoted in the Daily Mail as saying “Two years ago, I was spending 14 hours a day in bed and my brain was so fogged I couldn't write a letter. I wasn't functioning at all. I'd been diagnosed with chronic fatigue, but the doctors didn't have anything to offer. I had to employ a full-time nanny just to look after my three-year-old twins.” Now she is now back to coaching young Olympic hopefuls, has fired the nanny, and has started taking ballet lessons.
Participants Report “Soaring energy levels”
“When Donna came to see us, her energy levels were around 10 per cent of what she considered normal,” Professor Montoya was quoted as saying. “Today, she is functioning at 90 per cent.” A patient who could hardly walk all the way around the block is now bicycling for up to three hours each day. Another patient who could not even leave the bed now comes to breakfast every day at 7:00 AM.
CFS patients often have signs of pre-existing viral infections, and viral infections have even been thought to be “triggering events” for the onset of CFS in some patients. This is the first clinical study to indicate that treating one of the viral infections would also be effective in the underlying CFS symptoms.
“I was amazed by the results,” Professor Montoya was quoted as saying at the infectious diseases clinic he heads at Stanford University. “Donna was sent to me because high levels of another virus (Epstein Barr) had been detected in her system. I found high levels of HHV-6 virus as well, so I treated her with valganciclovir to bring down her viral load. I'd hoped it might help a bit, but I didn't expect the results to be anything so dramatic. It was pure serendipity.”
Careful Patient monitoring is needed
Valganciclovir is a prescription drug approved for treating HHV-6 infections of the eye, which can occur in individuals with severely weakened immune systems, such as transplant or cancer patients. The HHV-6 virus is not the same as the herpes simplex virus that causes cold sores. Most commonly, it is associated with a condition called roseola infantum, a fever and a rash in children.
“I have treated hundreds of immune compromised patients with the drug, so I am very familiar with it,” stated Professor Montoya in The Daily Mail. “It can have serious side-effects including anemia, so you have to monitor patients very carefully. But so far none of the CFS/ ME patients have reacted badly to it.” These preliminary results will have to be studied in many more patients before the drug valganciclovir can be used as a standard treatment.
Charles Shepherd, a medical advisor to the charity Action For ME (CFS is known as ME in England) told The Daily Mail that CFS/ME has long been associated with prior viral infections. “About 75 per cent of cases begin with an infection which the patient never properly recovers from, so it is quite likely infectious agents lurk in the body. While the role of HHV-6 is certainly plausible, we will have to wait for a larger trial that is properly controlled.”
Professor Montoya commented on the possibility that the results were just due to a placebo effect. He told the newspaper “that is unlikely because we saw a worsening of each patient's condition around week three to four of the treatment, probably when infected cells were dying off. After that came the improvement. That is not a pattern you get with placebos. But we don't know yet why the drug makes such a difference.”
The possibility that a drug has been found that could eventually provide an effective treatment for some patients with CFS is just one part of the puzzle being studied by researchers. Genetic research is also providing clues that may lead to new treatments and therapies.
Traditionally, it has been assumed that CFS had no known cause, no direct diagnosis, and no known cure. Some practitioners considered CFS symptoms to be “all in the head,” and recommended psychotherapy as the primary treatment.
Now research is showing that these patients have “a disturbance in their body's natural way of dealing with infection,” Professor Malcolm Hooper, Emeritus Professor of Medicinal Chemistry at the University of Sunderland told The Daily Mail. “Anti-viral drugs such as valganciclovir may be allowing it to re-set itself.”
Dr Jonathan Kerr of St George's Medical School in London, a published researcher on the interplay between gene activity and CFS/ME, told a recent symposium that “We've found that the genes in patients' white blood cells — a key part of the immune system — are switched on and off in an abnormal fashion.” A controlled research study on interferon beta, a relatively old drug, is in the planning stages to see if it can help restore the genetic balance. It is hoped that studies involving the interplay of viral infections, genetic action and immune system functioning will provide new options for the treatment of CFS patients and the management of CFS symptoms.

From my understanding of MS, its the combination of the immune system attacking myelin AND the permeability of the BBB. If they tested for both, I think we might see a different relationship. There has been plenty of discussion in the Tovaxin forum on how EVERYBODY could be found to produce MRTC's.


As for the anti-viral stuff.
The previous thread can be found at http://www.thisisms.com/ftopict-3517.html

The original article can be found at http://www.immunesupport.com/library/showarticle.cfm?ID=7152&Reviewed=YES

Also, I have read studies which have found ALCAR to be more effective for fatigue in MS http://www.direct-ms.org/pdf/DrugsMS/ALCAR%20for%20MS%20fatigue.pdf Which has an interesting paragraph

Thanks for the info, everyone. Sometimes I just feel like "carpet-bombing" MS -- I'd just like to take megadoses of every single anti-viral, antibiotic, vitamin, mineral, supplement and so on to see what happened... it might kill me, but at least I'd die healthy!

Dom.

You better be careful talking like this....some people may place you in the same category as they have placed me when it comes to "big pharma" and its control of MS drugs...and I'm not sure there is room for the two of us in the same category

Take care.

Harry

HarryZ said:



Sorry that you're leaving us Harry, but I'm sure it's for the best. I've found your comments about "big pharma" repetitive and you've given very little to this site in the last 18 months or so.

Harry Z said:



Sorry you feel that way Harry. I think everyone should be able to contribute and their views / comments should be respected.

No hard feelings Harry, I'll miss your interesting insights about Biogen and Tysabri. But if you've decided to quit this site then I respect your decision and wish you all the best.

Ian