Anti-EBV antibodies were detected in the CSF of patients with MS
Wonderfulworld wrote:VZV vaccine had already been manufactured. I remember that it's only effective for a dozen years or so. Too late to search and see if it's only effective before infection or not, it's way past my bedtime.
Let us know if you find anything L....even a dozen years might buy us a bit of time!
If anyone else can locate info on a substance that interferes with EBV let us know too.
Background: in 1992 or 1993 I was 2 years post-EBV and still feeling ill, but was working on a job and a colleague bought the Irish Times everyday. I remember reading an article that described a herb that blocked EBV (or Glandular Fever) in the blood. Try as I might, I can't find that article, even though the Irish Times archive is digitised here: http://www.irishtimes.com/search/archive.html odd but then again my research skills are not as sharp as they once were.
rainer wrote:A lot of EBV research that I have found points to the development of HSP-90 inhibitors mainly in relation to cancer.
There is a chart nearly at the bottom this page (http://www.gistsupport.org/ask-the-professional/hsp90-inhibitors-and-gist.php) with many of these inhibitors currently in trials.
Here is an abstract for one recent study relating HSP-90 inhibitors and MS. http://www.ncbi.nlm.nih.gov/pubmed/19948165
Identification of Natural Product Inhibitors of Hsp90 as Chemotherapeutic Agents
Principal Investigator: Robert Matts
Affiliation: Oklahoma State University
Abstract: Hsp90 is widely appreciated for its obligatory role in facilitating protein folding. Of the known Hsp90- dependent clients, 48 are directly related to oncogenesis, with Hsp90 clients being represented in all six hallmarks of cancer. Thus, inhibitors of Hsp90 provide a combinatorial attack that simultaneously derail multiple signaling cascades. Consequently, Hsp90 has emerged as an exciting new target for the development of anti-tumor agents. We have recently discovered that curcumin, a natural product found in Indian curry, inhibits Hsp90. In contrast to geldanamycin-derivatives that are currently in clinical trials, curcumin and its analogues can be easily synthesized for elucidation of structure-activity relationships and enhanced affinity for Hsp90. In addition, several other natural products that affect signaling pathways containing Hsp90-dependent proteins have been proposed to manifest their inhibitory activities through Hsp90 inhibition. Therefore, our specific aims are: 1) to identify new natural product inhibitors of Hsp90, libraries of natural products and their derivatives will be screened for their ability to inhibit the Hsp90- dependent refolding of luciferase and Hsp90's ATPase activity using assays developed in our laboratories; 2) to elucidate the biochemical mechanism of action of identified inhibitors by the use of in vitro assays that clearly differentiate whether molecules bind to Hsp90's N- or C-terminal ATP binding pocket (assays for Hsp90-dependent client maturation, pull down assays to determine effects on Hsp90/co-chaperone/client interactions, and protease fingerprints); 3) to determine the pharmacological properties of inhibitors in cancer cell lines by evaluation in anti-proliferative/ cytotoxicity assays, induction of Hsp90-dependent client protein degradation, and increased Hsp90 levels as hallmarks of Hsp90 inhibition; and 4) to elucidate structure-activity relationships for these inhibitors. Results from this work will identify new natural product inhibitors of Hsp90 and will provide more efficacious drugs that can be easily modified for increased potency against a wide range of cancers, and may lead to the development of more potent and less toxic chemotherapeutic agents. This proposal is innovative because for the first time, we will clearly show that the mechanism of action for natural products (e.g., curcumin) that are currently in clinical trials for the treatment of cancer act through Hsp90 inhibition.
Funding Period: 2009-09-30 - 2011-09-29
more information: NIH RePORT
Notably, Epstein-Barr virus-positive cells were present in much higher numbers in active MS lesions than expected in peripheral blood B cells, "which suggests that these cells are recruited to or accumulate in CNS infiltrates," Lünemann noted.
The investigators found that among patients with MS, anti-EBNA titers were much higher among smokers than among nonsmokers. In addition, the increased risk of MS associated with anti-EBNA was stronger among those who had ever smoked (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.7 – 5.7) compared with never smokers (OR, 1.8; 95% CI, 1.4 – 2.3; P value for interaction = .001).
By contrast, the association between smoking and MS was not present in individuals with low anti-EBNA titer levels. In addition, the risk of MS associated with smoking did not appear to be modified by HLA-DR15 gene status.
To my knowledge, there is not a well-described causative mechanism linking smoking and MS,” she said. “Possible mechanisms, such as neurotoxicity and immunomodulatory effects, have been suggested, but there is limited data on this topic.”
Asked for comment on these findings, Lily Jung, MD, with the Swedish Neuroscience Institute, in Seattle, Washington, added that recent studies show that not only does smoking increase risk of developing MS, it also increases magnetic resonance imaging lesion volume and brain atrophy and leads to faster progression of the disease.
gainsbourg wrote:That 2012 study Cheerleader just quoted was the turning point for me.
http://www.everydayhealth.com/multiple- ... in-ms.aspx
From that day on I have been completely certain herpes is the primary cause of MS (EBV is just one of several strains of herpes with a strong association with MS). I had being guessing for years that the mere presence of the herpes virus in nerve ganglia must somehow scare or trick the immune system into action, and this study backed up that hypothesis.
Until that study, almost all researchers had been saying "there's no evidence that herpes attacks myelin" - but since then, we've known for sure that it doesn't have to actually ATTACK. It somehow stimulates the immune system into a needless attack on healthy tissue.
For me it also explains the mystery of the stress/MS relapse relationship. Stress, in its many forms, often precedes herpes attacks. The white matter of the brain and CNS is like a telephone exchange conveying information from one part to another - stress logically puts an extra strain on this amazing system. Living creatures are very much like machines in some respects - certain types of strain or stress can eventually cause problems and damage.
Stress also calls into play huge changes inthe vascular system. Herpes viruses like EBV lie dormant in the base ganglia of the nerves - waiting for some kind of trigger or imbalance.
I am glad Cheerleader bumped this topic and believe that the day we learn how to eradicate herpes - through whatever means - will signal the end of MS
The association between EBV infection and CCSVI has not yet been explored; however, it could be hypothesized that venous stasis in the superior saggital sinus due to extracranial outflow impairment could affect the drainage of bridging veins that pass through the subarachnoid space (near the meninges and EBV-infected B-cell follicles) and contribute to EBV activation. The venous stasis hypothesis in the SSS may contribute to understanding why so many different viruses and bacteria [3,111] have been linked to increased MS susceptibility risk over the last 50 years.
"To date, there has been little interest in exploring the possibility that autoimmune responses to brain antigens might affect outcome from stroke. There are, however, studies that document the fact immune responses to brain antigens do occur following stroke.
For instance, lymphocytes from stroke survivors show more activity against MBP than the lymphocytes from patients with multiple sclerosis.
In summary, the nature of the postischemic immune response affects outcome from stroke (Figure). Modulation of this response may be a viable approach to improving outcome in stroke, but there are potential dangers associated with immunomodulation. A more complete understanding of the endogenous immune response following stroke is needed to safely manipulate this response in the poststroke period.
The evidence continues to mount that herpesviruses HHV-6A, EBV and VZV play an important role in triggering multiple sclerosis, perhaps in different subsets. Researchers at Oregon National Primate Research Center recently isolated a gamma herpesvirus that caused symptoms identical to MS in macaque monkeys. Alberto Ascherio at Harvard has shown that elevated EBV EBNA-1 antibodies are a marker for increased risk of MS, and researchers in Mexico recently found that VZV DNA is found in the CSF of 65% of MS patients with the progressive form and Chinese investigators found an increased incidence of MS the year after a VZV shingles attack.
The evidence for HHV-6A seems strongest of all the viruses implicated, although these viruses potentiate each other and co-infections and interaction with endogenous retroviruses appear to play a role as well. Over the past five years, European researchers have shown that HHV-6A can be isolated from the serum and CSF in a subset of MS patients during relapse, and have linked HHV-6A reactivation to two genes associated with an increased risk for MS: IRF5 and MHC2TA rs4774C.
Steve Jacobson at NINDS has shown that there is an increased lymphoproliferative response to HHV-6 and that there are HHV-6 and EBV specific oligoclonal bands in MS patients. Finally, the Spanish investigators also demonstrated that the effectiveness of interferon beta 1b treatment in MS patients correlates with HHV-6 DNA levels, suggesting that it is the antiviral action of the interferon beta treatment that causes the therapeutic effect. Jacobson’s group presented evidence at the last HHV-6 conference last winter that HHV-6A can cause MS-like neurological disease in monkeys (unpublished), and a group from France demonstrated that HHV-6A can cause mice to develop lesions in the brain.
Where is the MS community and why aren’t patients demanding clinical trials with antivirals? Clinicians at NYU tried valacyclovir (Valtrex) in 2005, but this was the wrong drug. Valtrex (which converts to acyclovir) is not effective for HHV-6. The rationale for a trial of valganciclovir (Valcyte) is compelling. It crosses the blood brain barrier, has a relatively good safety profile, and is effective against HHV-6A. FDA approved for CMV retinitis, Valcyte is an oral drug that can be used safely as long as patients are monitored for bone marrow suppression. It has been used routinely as prophylaxis for herpesvirus reactivation in the transplant community for over ten years, with minimal adverse side effects.
The HHV-6A may only be a bystander, and it may be that abortive infection (not actual replication) is what is important in triggering MS. That doesn’t mean an HHV-6 and EBV specific antivirals shouldn’t be given a try – especially in those with signs of viral activity (elevated IgG titers or virus specific oligoclonal bands). It is pretty clear now that interferon works for MS because of the antiviral effect, but it is a relatively weak antiviral compared to the others used for viral reactivation in transplant patients. What are neurologists waiting for?
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