Anonymoose wrote:Hi 1eye,
I don't know how Canadian health care works but maybe you could try getting an oncologist at a cancer center to give you the treatment. Adoptive immunotherapy is already used for some ebv related cancers...
I was going to try myself but seem to be doing quite well after rituxan/valtrex so I'm currently just sitting around waiting for my ms to act up before pursuing further treatment. There is a nih study in the US treating with intrathecal and iv rituxan (what I did with different dose schedule) that you might be able to get in on. It's obviously not the same as AI but would hit the same target.
I think exploring anti-ebv treatment is a fairly promising route to take. There are multiple options for doing so. If you want to go there, just keep trying.
GL!
From the Pender/Burroughs paper:
Prevention
Vaccination of healthy EBV-seronegative young adults with recombinant gp350 prevents the development of AIM induced by EBV infection, although it does not prevent asymptomatic infection.150 After vaccination, there was seroconversion to anti-gp350 antibodies persisting for >18 months and accounting for the protective effect, given that anti-gp350 antibody neutralizes EBV infectivity.151 Vaccination of rhesus monkeys with soluble rhesus lymphocryptovirus gp350 not only protects against infection but also reduces viral loads in animals that become infected with virus after challenge.152 As AIM increases the risk of MS,37 vaccination with gp350 might decrease the occurrence of MS by reducing the occurrence of AIM. By reducing the infectivity of EBV, it might prevent MS also in people who would not have developed AIM after EBV infection. Vaccination against EBV latent proteins also has the potential to prevent MS.
Treatment
There are 3 ways to treat MS by controlling EBV infection: (1) B-cell depletion with monoclonal antibodies, (2) antiviral drugs and (3) boosting immunity to EBV. B-cell depletion with rituximab reduces inflammatory brain lesions and clinical relapses in patients with relapsing–remitting MS141 but has the disadvantage of indiscriminately killing, not only EBV-infected B cells but also all uninfected B cells, thereby impairing protective humoral immunity against infectious agents, including EBV.
With regard to antiviral drugs, therapy with aciclovir, which inhibits herpesvirus DNA polymerase, 2.4 g daily for 2 years decreased the relapse rate by 34% in patients with relapsing–remitting MS (P=0.08).153 In a subsequent study, treatment with valaciclovir 3 g daily for 24 weeks reduced the number of new active MRI brain lesions in a subset of MS patients with high levels of MRI-evident disease activity.154 The limited efficacy of aciclovir and valaciclovir in MS might be due to the fact that these drugs act on EBV only when it is using its own DNA polymerase to replicate its DNA. This will apply only to lytically infected cells, but not to latently infected cells, which replicate EBV DNA by using EBNA1 to engage host-cell DNA polymerase. Thus, these antiviral drugs will inhibit EBV in only the minority of the EBV-infected B cells in the brain that are lytically infected but not in the majority that are latently infected.115 An alternative approach is to target the main latent proteins expressed by EBV-infected B cells in the brain in MS, namely LMP1, LMP2A and EBNA1.115, 127 This approach is exemplified by the use of small interfering RNA targeting the LMP1 gene to downregulate LMP1 expression and induce apoptosis in EBV-infected LCL,155 and by the use of small molecule inhibitors of EBNA1.156 Drugs inducing apoptosis of EBV-infected cells by inhibiting EBV-encoded anti-apoptotic proteins such as BHRF1157 might also be beneficial in the treatment of MS.
Improving immunity to EBV in people with MS could be achieved by vaccination with gp350 or EBV latent proteins, administration of humanized or human monoclonal antibody against gp350, or by the infusion of in vitro-expanded autologous EBV-specific CD8+ T cells. Treatment with autologous EBV-specific cytotoxic CD8+ T cells is beneficial in patients with EBV-induced post-transplantation lymphoproliferative disease158 and EBV-associated metastatic nasopharyngeal carcinoma.159 This approach should be feasible in MS because, despite the quantitative deficiency of EBV-specific CD8+ T cells, it is possible to generate EBV-specific CD8+ T-cell lines by in vitro stimulation with autologous LCL.75 Furthermore, EBV-infected B cells from MS patients are not resistant to killing by CD8+ T cells, because EBV-infected LCL from MS patients can be killed normally by HLA-matched EBV-specific CD8+ T-cell clones from healthy subjects, as well as by autologous EBV-specific CD8+ T-cell lines.75
AdE1-LMPpoly is a novel recombinant adenovirus vector encoding multiple CD8+ T-cell epitopes from three EBV latent proteins, namely EBNA1, LMP1 and LMP2A.159 Adoptive immunotherapy with autologous T cells expanded in vitro with AdE1-LMPpoly increases survival in patients with metastatic nasopharyngeal carcinoma, where the EBV-infected carcinoma cells express EBNA1, LMP1 and LMP2A.159 As EBV-infected B cells in the brain in MS express the same three EBV proteins,115, 127 adoptive immunotherapy with AdE1-LMPpoly might be an effective way to increase the number of CD8+ T cells available to eliminate EBV-infected B cells from the CNS in MS. Recently, this approach was used to treat a patient with secondary progressive MS.142 EBV-specific T cells from the patient’s blood were expanded by in vitro stimulation with AdE1-LMPpoly and interleukin-2. After expansion, 38.46% of CD8+ T cells, but only 0.22% of CD4+ T cells, reacted to the LMP peptides within AdE1-LMPpoly. The EBV-specific T cells were returned to the patient intravenously at fortnightly intervals. To reduce the risk of aggravating CNS inflammation, an initial dose of 5 × 106 T cells was administered, which is 25% of the median dose used for nasopharyngeal carcinoma,159 with gradual escalation of the dose over the following three infusions to 1 × 107, 1.5 × 107 and 2 × 107 cells. The treatment was successfully completed without significant adverse effects. Following the treatment, the patient experienced a reduction in fatigue and painful lower limb spasms, an improvement in cognition and hand function, and increased productivity at work. These improvements were sustained up to the time of the latest review, 21 weeks after the final T-cell infusion, when neurological examination demonstrated increased voluntary movement of the lower limbs. Following treatment, the frequency of circulating EBV-specific CD8+ T cells increased and there were decreases in intrathecal IgG production and disease activity on brain MRI.142 The beneficial effects of the therapy were attributed to the killing of EBV-infected B cells in the CNS by the adoptively transferred CD8+ T cells.
The adoptive transfer of EBV-specific CD8+ T cells in MS is not without risk. The transferred T cells could aggravate inflammation in the CNS and actually worsen MS, either through cross-reactivity between EBV and CNS antigens or through bystander damage. Clinical trials are needed to determine first the safety and then the efficacy of EBV-specific adoptive immunotherapy in a larger number of patients with progressive MS. In view of the potential risk of aggravating CNS inflammation, this therapy should probably not be tried yet in patients with relapsing–remitting MS, for which a number of disease-modifying therapies are already available.147 Another important question is how long any beneficial effect of EBV-specific adoptive immunotherapy in MS is likely to last. As the therapy does not correct the generalized CD8+ T-cell deficiency that might underlie the impaired CD8+ T-cell immunity to EBV in MS,77, 78 it is likely to be that EBV-specific CD8+ T-cell immunity might eventually wane again after the initial increase from immunotherapy. If such a decrease is accompanied by worsening of MS, consideration should be given to administering a further course of EBV-specific adoptive immunotherapy.
Conclusion
Given the rapidly accumulating evidence for a role of EBV in the pathogenesis of MS, there is ground for optimism that it might be possible to prevent and cure MS by effectively controlling EBV infection. Strategies to control EBV infection include vaccination against EBV, antiviral drugs and adoptive immunotherapy with EBV-specific cytotoxic CD8+ T cells.
Conflict of interest
SRB holds a patent on the EBV epitopes included in the AdE1-LMPpoly construct. MPP declares no conflicts of interest.
SRB is probably Dr. Scott Burroughs, and MPP would be Dr. Pender.
Health care in Canada is very insular and sensitive to turf trespassers. The attitude I have seen is that since "MS" is not considered as a fatal condition, there can be no off-label or experimental treatment for it. Basically the "MS" group of patiemts is seen as a gravy train for the drug/research medico-industrial complex. It is not meddled with, without all i's dotted, t's crossed, all three phases of trials, and approval by the FDA and Health Canada. If I could find such an oncologist or anybody willing to administer some kind of EVB targeted therapy, it would likely be in the US, and cost me a lot of money, even though I am supposedly insured. I could not only be playing guitar, I could be driving to the six-figure job I had, but the insurance company won't move without the medical mafia's approval.
I would be better off in the country of my birth.
Can I get my kids vaccinated?
There are those who are shot and killed in the hours before an armistice comes into force.
This unit of entertainment not brought to you by FREMULON.
Not a doctor.
"I'm still here, how 'bout that? I may have lost my lunchbox, but I'm still here." John Cowan Hartford (December 30, 1937 – June 4, 2001)