There was article published recently about the role of a receptor - CD8 and how it malfunctions in people with MS.
"What is remarkable about the CD8 T cell deficiency in MS is that normally when the EBV load is increased, as it is in the blood and brain of MS patients, the CD8 T cell frequency should increase and not decrease. This suggests that there is a fundamental defect in the ability of MS patients to make an appropriate CD8 T cell response to EBV, as we have previously hypothesised. We propose that this defect is genetically determined. "
http://jnnp.bmj.com/content/early/2011/ ... 00213.long
In simple terms, when an EBV infection is detected in a healthy immune system the receptor CD8 begins to express interferon and other antiviral activity which triggers the immune sytem to fight off a viral infection.
Interferon comes from the same root word as “interfere”. Its role is to allow communication between cells to alert the immune system to fight of a viral infection. Aching muscles and fever are the manifestation of elevated interferon levels in normal illness and injections like Avonex are stimulating the same response.
Some viruses have evolved so they disrupt the signal to the immune system from the interferon. The research suggests that people with MS have CD8 T cell receptors that fail to make the appropriate natural interferon response when exposed to EBV. When the EBV load increases people with MS produce a lower CD8 response and hence send fewer signals to the immune system to fight the virus. The opposite happens in the rest of the population so they stay well.
The important thing is two variables have been identified; 1) we don’t always make an appropriate interferon response to viral infection and 2) EBV is an example of a virus that we can’t handle ourselves.
There is a long but useful note on other viruses and interferon here-
I don’t claim any scientific capability but I have been staying well for 16 years now by doing two things-
1) Injecting Avonex (interferon Beta 1A) weekly. I know and accept this is a horrible injection
2) Taking two tablets per day of Avonex because it specifically attacks herpes family virus replication
In effect, I have been doing exactly what the science in the above article would point to how we should stabilise ourselves. I boost my levels of Interferon to fight infection because my CD8 receptor won’t tell my body to do it itself and I limit the EBV by disrupting its replication cycle.
What I do is hard and uncomfortable for up to 36 hours after an injection but I have no noticeable MS problems.
The Avonex on its own can’t do the job because it doesn’t stop the ongoing increase in the viral load. The Valtrex on its own can’t do the job because it can’t signal the immune system. If I use both, I signal the immune system and I am continuously attack the underlying virus. I am staying well.
This is such an inexact approach I can’t guarantee that exactly what I do will work for you but some variation on the theme might help as long as you create an elevated interferon level and disrupt the viral cycle.
Hope this helps somebody.
To quote from the last page -
In a subsequent study, treatment with valaciclovir, a prodrug
of aciclovir that increases aciclovir bioavailability, 3
g daily for 24 weeks reduced the number of new active
MRI brain lesions in a subgroup of patients with relapsing–
remitting MS who had high levels of MRI-evident
disease activity (Bech and others 2002). The limited efficacy
of aciclovir and valaciclovir in the treatment of MS
might be explained by 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
through the use of EBNA1 to engage host cell DNA polymerase.
Valtrex works against Epstein Barr Virus, which causes fatigue, so are you fatigue free now. I have never had fatigue but I have never had glandular fever, coldsores, even chickenpox or shingles, so I presume that I am immune. My friend has fatigue and she also had Glandular fever when she was a child.
Have a blood test. I think you will find you have at least one of those viruses.
I did have significant fatigue which I have overcome some years back on my regime. Recently I have reviewed what I have being doing as a result of developing gout. As I have mentioned in earlier posts the probablity of having both gout and MS is very very low. People with MS have significantly lower Uric acid than the normal range and that makes gout an impossiblity except you have purine loaded with Valtrex daily for 10 years (1 gram a day if you want to try).
I've taken some very strong medication to lower my Uric acid level and I have started to notice a bit of fatigue as a consequence. This needs further investigation before any conclusion can be drawn but it is interesting.
I might well do that, I'm just interested why my friend has devestating fatigue and not me.
You are right its all very interesting.
If you do get some tests try these ones; EBV serology, 25 hydroxyvitamin d and uric acid levels. If your friend goes to the same doctor get the same tests done and compare both sets against what the doctor says are normal. Having just played around with my Uric acid levels I'm quite surprised with the increase in the sense of fatigue and altered skin sensation as the uric acid fell. I've just done another Uric acid test yesterday and I think I should do another one in a week to see where it stabilises before I start playing around again. My feeling is if I can take just enough Valtrex to keep my Uric acid in a normal range and take a gout relief medication to stop xanthene oxidising into uric acid I might end up in the right spot. Who knows! I'll let you know how I go.
Well it's been a few now and I have a much clearer idea of why my combination of Valtrex and Avonex seems to work. I tried a period of taking nothing at all to see what would happen and soon discovered I needed to be back on the combination which proves to me that what I do keeps the beast in its cage but doesn't cure. After some intensive research I think the mechanism at work goes something like this.
We have a genetic predisposition towards being unable to properly respond to EBV infection due to a gene (or number of genes) called a HERV. When we are infected with EBV it migrates to the tonsillar tissue where it binds to autoreactive B cells. In the first 24 hours of infection it is possible to interrupt the EBV but after but after that time it has formed a complex capsid around its enzymes that protect it from being attacked by the T Cells in our immune system. The EBV infected B cells can migrate through the CNS and they produce two molecules of oxygen (O2) known as Superoxide. This product also occurs naturally in the body. The CNS and brain in particular produce Nitric Oxide under normal conditions. The problem occurs when the two oxides come into close contact with each other the spontaneously produce the substance Peroxynitrate. This is very cytotoxic and the amount produced rises by upto 1,000,000 times the normal level in the body.
Peroxynitrate disables many function including ATP which drives the production of energy in cells, the dehydatase enzymes which are required to produce adequate quantities of nonessential amino acids (the ones we make ourselves) and the VDR (vitamin D receptor). It is strongly associated with Chronic fatigue, Lymphoma and other diseases in medical papers. Peroxynitrate is neurotoxic and can be found in glial scars (the white stuff in our brains).
Theorectically, wiping out the B cells would remove the EBV as that is where it resides but that is a fairly dangerous thing to do.
Valtrex is basically a guanine base that binds to the cysteine in the EBV RNA at the time of replication and prevents it replicating when a fresh cell is made. As the effective life of a tablet is less than 15 hours its hard to get all the virus at the point of replication but it does slow the process down. A short course wont do a thing. It will take years of constant use to get to where I am. The EBV immortalises the infected B cells which can produce daughter cells to help the virus persist so constant use of Valtrex is needed.
Avonex, Interferon Beta 1a, is a type 1 interferon that signals the immune system to attack an invader. EBV as a prymidine loaded virus can hide from the immune system and not trigger the normal interferon response so the injection is necessary to keep the immune system on alert. Taking Interferon is the absolute opposite of taking steroids. It is infinitely better for the immune system to be up and about all the time than bombed out by steroids. The neurologist who first put me on Avonex told me it was downregulating a part of my immune system. He was completely wrong. Interferon comes from the same root word as interfere. It's a signalling agent to fire things up and its very important as it can trigger an attack on budding EBV before the capsid is secure. That's what firing up the immune system is all about. The reason we often feel so bad on Interferon is the immune system will also attack any other underlying infection as well when it is on alert.
My combination has been successful in turning off MS but as Valtrex is a Purine nucleotide analogue I have basically been loading my system with a gram a day of purine and elevated purine levels lead to high Uric acid which causes gout. Uric acid is a scavenger of Peroxynitrate so I need a high level but just below gouty levels. If you have MS you have very low Uric Acid levels due to impaired ATP production.
I have added a part of simple gout medication called Probenecid into my regime as that keeps the uric acid circulating rather than being absorbed into the body and crystalising. It also extends the functional life of medications so I am getting better 24 hour coverage from the Valtrex now and extended life from the Avonex injection.
I have also read that All trans retinoic Acid can inactivate EBV. That a form of Vitamin A. As this vitamin can accumulate in the system and cause problems I have decided to try a glass of fresh carrot juice ech day as a safer option and I will see if that does anything after a while. Overall I feel very well.
Hope this ramble helps someone.
Something else I found interesting about your post are the supplements I take which I know have helped my fatigue/MS. Q10 200mg daily which is involved with ATP, Beta carotene (precursor to vitamin A without having the danger of overdosing), Vitamin D. (I also take folic acid 400ug Bromelain and vit C)
I have had mono (glandular fever) twice and both times very badly, it went to my liver and caused severe inflammation (I had to be hospitalised) and I def think it is still circulating especially in my liver. Not sure what my uric acid levels are but might get em tested.
Thanks for keeping us updated x
I'd check for EBV as well as CMV. You may have both but as you can see they classify differently so the outcomes may differ.
HHV Sub-Family Genus Alternative name Growth Cycle Cytopathology Site of Latency
1 Alpha- Simplexvirus Herpes-Simplex 1 (HSV-1) Short (<24 Hours) Cytolytic Sensory ganglia and
2 Alpha- Simplexvirus Herpes-Simplex 2 (HSV-2) Short (<24 Hours) Cytolytic Sensory ganglia and
3 Alpha- Simplexvirus Varicella Zoster virus (VSV) Short (<24 Hours) Cytolytic Sensory ganglia and
4 Gamma- Lymphocrytovirus Epstein-Barr virus (EBV) Variable Lymphoproliferative Lymphocytes
5 Beta Cytomegalovirus Human Cytomegalovirus (HCMV)Long (>24 hours)Cytomegalic Glands Kidney
6 Beta Roseolovirus ---------------- Long (>24 hours) Lymphoproliferative Lymphoid tissue
7 Beta Roseolovirus ---------------- Long (>24 hours) Lymphoproliferative Lymphoid tissue
8 Gamma- Rhadinovirus Kaposi’s Sarcoma-associated Herpes Virus (KSHV)Variable Lymphoproliferative Lymphocytes
Sorry about the formatting but that's the best I can do on this board
Are you taking Carrot Juice or a supplement to get the Vit A? I've developed quite a "frog in the throat" since I started taking Carrot juice daily. It's a bit like the throat you get before a cold sets in and its a bit sore. I'm hoping it's caused by EBV infected B cells disliking the exposure to the retinoic acid and kicking up a reaction. Hopefully that means something good happens. The discomfort is limited to the tonsil tissues otherwise I feel fine. I like your logic for using coenzyme Q10 to boost ATP so I've added that as well. If all this keeps me well then my regime has really become 2 valtrex tablets per day, 2 Probenecid tablets per day, 1 coenzyme Q10 (150mg) per day and a big glass of fresh carrot juice with a bit of ginger for taste and each week 1 Avonex injection.
My previous post about the different Herpes virus had a very garbled layout (sorry). EBV and CMV are different so I'm sure what I do works for EBV based MS but it might differ if CMV is your underlying trigger. I imagine the Valtrex will still work on CMV but I haven't read how CMV can infect B cells anywhere. I'm assuming you probably have positive IgG test results for both. I am negative for CMV.
Just a little update so anyone who is interested in my approach can see how I'm going. In a nutshell, I am staying well.
I've learned that EBV can follow two different cyles; the lytic cycle where the host cell ultimately bursts seeding daughter infected B cells (a process called budding) and the latent cycle where there is no budding but as the host cells divides they produce new cells each carry the EBV infection. This difference may help explain the different progression of Primary progressive and remitting relapsing MS. I'm not sure which form is more problematic for disease progression. It seems to me that the lytic phase can be modified by constant acyclovir use and the latent phase responds best to Interferon. If the the two phases coexist or are interchangeable then both Interferon and acyclovir are needed as they work differently. The key point is they work as the virus replicates and there is only a short window at replication so both methods are needed constantly.
I'm sure that a glass of carrot juice a day is really important. The are two retinoic acids in this juice; all-trans retinoic acid which is capable of making holes in the EBV capsid and the virus becomes susceptible to attack by the T cells and 9-cis retinoic acid. The latter retinoid is needed to activate the retinoid X receptor. This receptor needs to be working for the Vitamin D receptor to work. You can't have one without the other. It may be that a malfunctioning VDR is just a symptom of an underlying issue the same as I found a low uric acid level and low levels of non essential amino acids were. Naturally you can treat the symptom but I would rather attack the cause. When I think I have given it enough time I will get my VDR and non essential amino acid levels rechecked to see if anything is happening. Check RXR on wikipedia and see how many functions it controls. It's a critical issue but the focus is on VDR and it may be not the right place to look. You can elevate VDR function with drugs but there are side effects and some of these medications require no interferon to be taken.
I found the carrot juice caused such a profound buildup of mucous and I needed an antibiotic. After 4 weeks I was fine again. I think I may have done some good as I have tried taking no medication and have stayed well for several weeks. I'm too gutless to stay on that path so I am starting Valtrex from tomorrow. There are Christmas holidays in Australia and its summer so I always take a holiday from Avonex at this time as I hate taking the injection away with me.
I'll let you know how I am going in a few months.
Thanks for the update.
I was taking beta carotene but have stopped for a while. I also found 200mg Q10 too strong daily so I take it twice a week.
I think I might give Valtrex a shot (if my dr is willing to prescribe) I am on copaxone at the moment, and LDN (plus my blood thinners still) so I need to drop something..maybe vits etc to add valtrex.
Glad you are doing well still...nice to hear some good news:) x
Did you get a test for EBV to see if you are IgG positive? If your problem is CMV rather than EBV then Valtrex will help but they usually use Gangliovir to treat CMV. Both herpes viruses are lymphoproliferative but Gangliovir might be better for CMV. Very similar but marginally different action at work.
I'd also suggest you get your nonessential amino acids checked. It might be possible to boost those to give you a better response.
I think you need to check your blood thinner. Some contraindicate with Co enzyme Q10. I think this is the cause of the difficulty handling the Q10. On it's own it's super safe.
See http://www.drugs.com/drug-interactions/ ... e-q10.html
I found doctors don't look hard enough for contraindications. My own, and he's really great, failed to pick up that part of the gout medication I was on (allopurinol) would contraindicate with Valtrex. They really are not that good at chemistry so you always have to check. I would discuss blood thinners and contraindications in great detail with your doctor. If you get a brush off find another doctor.
I have had me/cfs for 10 yrs commonly known as chronic fatigue syndrome but a very misunderstood illness. I came across this site googling viral treatments and was suprised at the similarities in this thread with the immune/infectious abnormalities with many of the MS people have in common with cfs/me.
Its interesting to see some responding to antivirals which many do with cfs although not a cure, also the abnormalities in cd8, b-cells. A recent treatment trial in Norway with cfs people with rituximab which knocks out the b-cells has seen major improvements in cfs patients, many almost back to 100% function and some from a bedridden state.
I myself have improved with the antiviral famvir and have chronically elevated lymphocytes especially cd8 t-cells which my doc suspects is due to ebv and cmv reactivating. Also what maybe of interest is that Bond university on the goldcoast have done a study on cfs patients over an 18month period on their natural killer cell function (not numbers as these can be normal) and what they are finding is that people with cfs have very poor Nk function. This leaves us open to many chronic infections and viruses common to the community and supressed by healthy immune systems are reactivating in cfs patients. They also found cd8 t-cells also function poorly.
I think many of these viruses and immune dysfunctions are common in many illnesses and find it very interesting how similar symptoms MS patients have to cfs patients with neurological symptoms and symptoms that are very up and down. I look forward to reading more here and maybe finding information relevant to cfs/me that can help myself.
here is some links on antiviral treatments in cfs/me etc that maybe of interest.
http://phoenixrising.me/interviews-3/le ... rt-johnson
http://www.translational-medicine.com/c ... 6-9-81.pdf
http://www.wpinstitute.org/news/docs/me ... iteria.pdf
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