This Is MS Multiple Sclerosis Community: Knowledge & Support

I posted a similar article last week, but this was posted on the NMSS website today.

http://www.nationalmssociety.org/site/P ... h_2007nov5

The abstract:


http://www.jem.org/cgi/content/abstract/jem.20071030v1

Prof Giovannoni in the UK is also looking at the role of EBV and MS and is being funded by the UK MS Society (there are similar funded projects in Australia and the US).

Prof Compston, who with Dr Coles are the lead investigators on the Campath trial, has also said that EBV may have a role.

Viruses are complex beasts as was shown in some research last week on Hep C and also recent research on cold sores and Alzheimer's. But finding out if, and how, they play a role in MS will be a big step forward.

Ian

Some early press coverage on this research.

http://c.moreover.com/click/here.pl?j11 ... 3&w=464753

bromley,

If EBV is indeed the cause, do you have any idea how the disease could be treated?

The articles don't talk about this problem. To the best of my knowledge, EBV not treatable.

gwa

GWA,

There isn't (yet) a vaccine for EBV. I'm not sure about anti-virals (I think some are in development).

Perhaps the approach will be to target the B cells in some way (which might explain why Rituximab looks promising).


I imagine that the treatments in trial to provide neuro-protection and repair will still be relevant for people with MS. In the future, if EBV is proved to be a trigger or cause, vaccination would prevent people from getting EBV and, therefore, MS.

It's early days, but I think we may see a lot of interesting research in this area.

Ian

Ian

Thanks as always for the info. Here's some info about DHEA and EBV that I've never posted because I'm not certain if it's relevant or what it means. I still don't but thought I'd offer the "hormone" angle to the EBV discussion.

Dehydroepiandrosterone and 16 alpha-bromo-epiandrosterone: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes

If anyone could comment on whether or not this might be relevant that would be nice. DHEA is consistently low in people with MS and drops most dramatically between the ages of 20-40.

Thanks

Sharon

Here is a list of anti-virals that are used to treat members of the Herpes family of which EBV is one of the viruses.

http://www.merck.com/mmpe/sec14/ch189/ch189a.html

I need a little help with understanding this...I thought that a vaccine normally consists of the virus or bacteria or a similar one that causes the illness but in a form that keeps you from getting a full blown case of it. Just enough to give your immune system the ability to make the memory cells to fight it off in the future. If this is true, won't you maybe cause ms in people if this is indeed true about ebv and ms?

I'm well educated in the computer sciences but not in the biological sciences. Somebody please explain this to me.

Marcia

These are anti-virals, not vaccines. Just like anti-bacterials (eg penicillin) are not vaccines.

I'm sorry I wasn't clearer in my question. I was thinking about the idea of a vaccination for EBV.

I am going to begin what I believe will be a very long post with my own personal experiences.
After my diagnosis with ms, and a circus-like experience with the neuro's office (there were clowns everywhere), I went to a holistic doctor. We tried a few homeopathic remedies and settled on one, because the remedy caused a reaction in my body. The reaction? A rash around my neck (itchy) and fever blisters. I take the remedy an average of once each 6 weeks, and only one time did I not get the rash and fever blisters. He did finally tell me to dilute the remedy a bit more so the reaction wouldn't be so strong. I still get the fever blisters.
The basic theory of homeopathic remedies- to heal from the core- the center. The chi, life force, sounds silly, doesn't it. I think I am a believer.
He says we spend so much time treating symptoms with steroids, etc (which I took re my neouro's advice) and says we are actually doing is driving the disease inward. Covering up symptoms and driving the basic problem further into the body.
Homeopathic remedies treat "from the inside out- from the top to the bottom- or in reverse of the timeline that the problems manifested themselves". (or in a mix of these)
There is a story he told me about a civil war soldier who was shot with a musket ball. The ball lodged inthe mans lung and could not be removed. Years later, the man, for another ailment, took a homeopathic remedy and began to have chest pain. The musket ball worked itself OUT of his body.
So, back to my experience.
I have had alopecia areata (an autoimmune issue they say) since about 1986. My hair comes out in circles- comes and goes in different spots. After the fever blister/ remedy experience, I began to read, and herpes virus lives in the hair root. Not the hair itself, not the bulb, (picture an onion) but inthe roots below the bulb. (again, picture an onion). Could it be that my immune system was doing what it was supposed to do and it was fighting the herpes virus? My hair, then, just a casualty of that war.
I have had fever blisters since I was a child, but because of the idea behind homeopathy and my reaction to it, I began to read of the relation to herpes and the nervous system. Herpes hide in the nerves, so again, could it be that my immune system is doing what it is supposed to do, trying to attack the herpes in my nerves, and the myelin is again a casualty of that war?
There are countless aticles out there pointing to different herpes type viruses being found in MS patients and cadavers of those who had ms.
I asked my doc if the remedy would rid my body of the virus, and he doesn't know. I have an appointment for blood work onthe 20th, and will ask him if he can test for the amount of herpes in me. If he can, I'll wait awhile and have him test again. Less the second time is what I'm hoping for.
Doc says that seldom are skin type issues life threatening, so if you can begin to get the issue inside to come back to the surface and leave the inside alone, you are on a good track.
I know all this sounds a little odd, but my own experience points to herpes as an issue in my MS.
EBV is a herpes virus, and I will post a small HhV-6 article here. My HSV-1 (fever blister) virus is closely related to HSV-2 and there are articles on those and MS as well. I even read that some people with the HSV-2 (genital herpes) develope leg numbness like ms during flare-ups.
A very large portion of the general population carries the herpes virus, many without knowing so- no outward manifestation of the virus. So, if my remedy has pointed me in the proper direction, my question is why do I and others develope ms because of it and most people do not.
Here is the artlicle I said I'd post.



More Evidence Points to Direct Involvement of HHV-6 in MS Pathogenesis

By Karla Gale

NEW YORK (Reuters Health) May 09 - Powerful molecular techniques used to evaluate brain tissue at different stages in the development of multiple sclerosis (MS) support the theory that human herpesvirus 6 (HHV-6) is present in MS lesions and may be actively involved in disease pathology, according to two reports in the Journal of Infectious Diseases for May 1. The first study established that HHV-6 DNA is present at high frequencies in glial cells of acute-phase lesions in patients with MS. In the second report, HHV-6 was significantly more common in MS plaques than in normal-appearing white matter of patients with long-standing MS, healthy control subjects, or brains individuals with other neurologic diseases. The results are so powerful that the two research groups are now in the planning stages of a clinical trial to test the efficacy of antiviral agents for treatment of MS. Dr. Andrew D. Goodman and colleagues at the University of Rochester School of Medicine and Dentistry, New York, obtained biopsy specimens of lesions that presented as cerebral tumors in 5 patients subsequently diagnosed with MS. None had received immunomodulatory therapy at the time of biopsy. A sensitive in situ polymerase chain reaction (ISPCR) method recently developed by Dr. Goodman's group revealed HHV-6 DNA in oligodendrocytes, lymphocytes and microglia in all five lesions. "In our study, viral DNA does locate to oligodendrocytes, the cells that make the myelin that is the target of inflammation," Dr. Goodman told Reuters Health. "The implication is that this could be the target of the immune response that causes inflammation and ultimately scars the nervous system." What is unique about the University of Rochester study, he added, is that the findings "couldn't have been impacted by treatment or years of chronic illness."
Dr. Goodman cautioned that his group's study "does not provide evidence of direct active infection" because they only found latent virus, and his group has yet to test tissue for the presence of other viral agents. "But other groups have previously reported active infection," he added, and his laboratory is close to developing ISPCR tests for additional herpes and non-herpes viruses.
Meanwhile, Dr. Steven Jacobson and colleagues, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, examined the frequency of HHV-6 DNA in brain tissue samples from MS patients, both MS plaques and normal-appearing white matter (NAWM), as well as from patients with non-MS brain disorders and from healthy control subjects.
They obtained 64 samples from 30 MS plaques of 13 patients with MS, as well as 44 samples of NAWM from 10 of the same patients. Thirty-seven (75.8%) MS plaques and seven (15.9%) NAWM samples were positive for HHV-6 specific DNA sequences, a significant difference (p < 0.0005). "The NAWM specimens...were dissected in close proximity to lesion areas, suggesting that HHV-6 positivity is associated with MS lesions in particular, rather than with brain regions where lesions are common," writes the NIH research group.
The frequency in MS plaques was also significantly higher than in samples from 12 pathologically normal brains (26.8%; p > 0.0170) and in 13 patients with other neurologic diseases (21.7%; p > 0.003). Results of both studies suggest that "the increased presence of HHV-6 DNA may not be reflective of a generalized reactivation that may occur during neuroinflammation," Dr. Jacobson and his colleagues note. In an interview with Reuters Health, Dr. Jacobson remarked that genital and oral herpes virus infections are known to cycle through quiescent and reactivated states. He postulated, "Could a similar process be occurring in MS?" Positive results from clinical trials testing antiviral drugs would provide supportive evidence that HHV-6 is actively involved in the disease process, he said. "But there are a lot of nitty-gritty details to be worked out" before clinical trials can be conducted, such as type of patients to include and how to monitor clinical efficacy, including reduction in MRI lesion load, disease course, or reduction and viral load.
J Infect Dis 2003;187:1365-1387.
It may well be that other gram negative pathogens or viruses can ALSO trigger MS (symptoms result from destruction of myelin sheath which results from Mg deficiency caused by an infection - bacterial or viral). Most pathogens are metalloproteases. Same treatment applies. ction and viral load.
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ALSO, let me tell you this. I was about 6 when my parents were helping my relatives move, and I got my toe caught in the moving truck lift. Since then, for all of 40 years, I have had a black toenail. Since taking the homeopathic remedy, my nail is clearing. 75% healthy. Not anything to do with ms or herpes, but a sure sign to me that the remedy is working out problems I have had for a long long time.

Also, let me day that my doc has NEVER said that my ms is caused by herpes. He doesn't go there at all. He treats and asks about reactions and treats more. He is a very intelligent man, yet says the whole idea of the homepathic proccess is mind boggling to him.

I told him one day that I want all ms symptoms to go away- the daily reminders of ms haunt me. He admits that may never happen, but tells me he has had one ms patient for 20 years and the biggest problem that man has is that sometimes he can't button his buttons.
I don't know. What do you all think?

Terry

If conventional approaches fail to come up with an antiviral or viral vaccine, the area of NanoViricides, (using nano technology to deliver the killer blow), is looking very exciting.

Sharon, in the immune suppressed EBV can cause lymphoproliferative disorder and has been associated with some forms of cancer – since the link at the top of your extract says "carcinogenesis", I'm wondering if the virus causes the white blood cells to change shape and therefore persist, or function incorrectly and contribute to MS?
Marcia, I see your point about vaccines but some vaccines don't use the entire virus or bacterium, only protein fragments, so hopefully wouldn't cause the reaction you describe. If an attenuated or killed virus is used I don't think it would be capable of invading the B cells and causing the shape change described above, but I'm not 100% sure!

_________________
Dom

Thanks Dom



That makes sense to me to the extent that this company is developing what I am convinced are "forms" of DHEA for clinical use and one of the applications is cancer. Another is "auto-immune" disorders--including some work on MS (diabetes and insulin resistance too Lynda Carol).

Take care

Sharon

.

I think this is extremely important!
The results are very strong - 21 out of 22 samples from (deceased) MS patients were positive for EBV, and none(!) of the samples from other inflammatory brain conditions showed it.
Also, a new form of tertiary lymphatic tissue, containing EBV-specific B cells was found near the meninges.
Although it is no proof, The most parsimonious explanation for this is that EBV is involved in triggering MS.
This is real hope for treatment and prevention.
Lately it was suggested that valacyclovir can control EBV in mononucleosis.
Perhaps sown the line combination therapies, like the one used for HIV can fully control it.
There haven't been much effort in this direction because EBV is so benign (the worst people get is Mononucleosis.

Balfour HH Jr, Hokanson KM, Schacherer RM, Fietzer CM, Schmeling DO, Holman CJ, Vezina HE, Brundage RC.
A virologic pilot study of valacyclovir in infectious mononucleosis.
J Clin Virol. 2007 May;39(1):16-21.

DrGuy, valacyclovir has been tested in people with MS.



A randomized clinical trial of valacyclovir in multiple sclerosis.

Mult Scler. 2005 Jun;11(3):286-95.
Friedman JE, Zabriskie JB, Plank C, Ablashi D, Whitman J, Shahan B, Edgell R, Shieh M, Rapalino O, Zimmerman R, Sheng D.
Department of Neurology, New York University School of Medicine, NY, NY 10010, USA. jef4@med.nyu.edu

OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).

DESIGN/METHODS: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.

RESULTS: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.

CONCLUSIONS: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.

Pubmed link



A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS.

Neurology. 2002 Jan 8;58(1):31-6.
Comment in: Neurology. 2002 Jan 8;58(1):7-8.
Summary for patients in: Curr Neurol Neurosci Rep. 2002 May;2(3):257-8.
Bech E, Lycke J, Gadeberg P, Hansen HJ, Malmeström C, Andersen O, Christensen T, Ekholm S, Haahr S, Höllsberg P, Bergström T, Svennerholm B, Jakobsen J.
Department of Neurology, Aarhus University Hospital, Denmark.

OBJECTIVE: To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2, randomized, double-blind, placebo-controlled study.

BACKGROUND: It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS.

METHODS: Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment. Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir (n = 36) or placebo (n = 34) three times daily for 24 weeks. Patients underwent MRI every fourth week for 32 weeks: twice during pretreatment, six times during treatment, and once after treatment. Scoring of neurologic disability was performed at the start and end of the treatment period. The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment. Secondary endpoints included other MRI measures and clinical endpoints.

RESULTS: The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4. A protocol-planned exploratory analysis stratified patients according to baseline activity; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group (n = 17) developed fewer new active lesions per scan than did those in the placebo treatment group (n = 11). The median number (Q(1), Q(3) range) of active lesions was 2.0 (1.38, 3.96) in the valacyclovir treatment group and 6.5 (2.63, 9.0) in the placebo treatment group.

CONCLUSIONS: Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period. In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks, valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions. The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity.

Pubmed link