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Immunotherapy against EBV: Targeting EBV infected cells using immunotherapy

Ecoclimber

Senior Member
Messages
1,011

There has been interesting discussion recently concerning EBV as a possible etiology in ME/CFS. This blog article is from the UK MS Research Blog at Barts and the London School of Medicine and Dentistry with prior permission to repost from Prof. Gavin Giovannoni. I thought it would be of interest to the community.

"If you have been following this blog you will know that I am a firm believer that EBV causes MS. I say believer because when you apply Bradford-Hill's criteria for causation we are not quite there yet.

We need experimental proof that EBV causes MS and we need to understand how EBV interacts with the human biology to trigger or drive MS. EBV also has the explain everything we know about the epidemiology of the disease; for example the worldwide distribution of the disease, sex ratio, month of birth effect, parent-of-origin effect, changing incidence of the disease, treatment response to various classes of drugs, etc."
"I say EBV trigger or EBV driver because we don't know if EBV acts early in the causal pathway as a hit and run agent that triggers MS and then MS runs amok without the need for an ongoing role of the virus.

In comparison the driver hypothesis is that EBV drives the disease and is needed throughout the course of the disease. If the latter is the case then we can target EBV with drugs or other anti-viral strategies to treat MS. This is what we are trying to achieve with the Charcot Project; the drugs we are choosing all target EBV or downstream events triggered by EBV."

"The case study below from Michael Pender's group supports an ongoing role for EBV in MS. They took CD8+ T cells from a SPMSer and supercharged them in the lab. These CD8+ T cells (a type of white blood cell) are akin to heat-seeking killer missiles that are targeted to EBV-infected cells within the body; they find these cells and kill them releasing proteins that literally punch holes in infected cells.

The treatment was safe without any adverse events and remarkably the MSer improved. One swallow does not make a summer and this study will need to be repeated on a larger number of MSers. If this treatment is found to be safe it needs to be tested in a double-blind placebo-controlled study. I would suggest that instead of a placebo that an active control is used, for example CD8+ T cells directed at non-EBV viral proteins. The actve control is to make sure that the treatment response is not non-specific, i.e. simply due to something related to the infusion of activated T-cells."

"Why is this research so important? Simply because it is challenging the current autoimmune dogma about MS that has a lot of holes in it. It is also part of the experimental evidence we need to prove that EBV is the cause of MS.
Can you imagine what this would do to the field of MS? What it will do to the treatment of MS? What it will do the market of MS DMTs? This could be the black swan moment I have been waiting for. In my mind it is not a question about whether a black swan will land, but when."

"For those of you confused by this talk of black swans should read my earlier posts on the subject."


Multiple Sclerosis Research: What does a black swan have to do ..., 06 Sep 2013; A good book to read about these improbable events is 'The Black Swan: The Impact of the Highly Improbable' by Nassim Taleb. The book focuses on the extreme impact of certain kinds of rare and unpredictable events ...
black_swan_by_sarahlouisejohnson-d4f3h2u.jpg

Who said a black swan has to look and feel like a feathered bird?
"I would like to congratulate and thank Michael Pender and his colleagues for pursuing this work. You are brave people and your pioneering attitude and commitment to this field of work is much admired and appreciated. Please keep up the good work."

Pender et al. Epstein–Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis Mult Sclerosis Journal Epub

Defective control of Epstein–Barr virus (EBV) infection by cytotoxic CD8+ T cells might predispose to multiple sclerosis (MS) by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. We have treated a patient with secondary progressive MS with in vitro-expanded autologous EBV-specific CD8+ T cells directed against viral latent proteins.

This adoptive immunotherapy had no adverse effects and the patient showed clinical improvement with reduced disease activity on magnetic resonance imaging and decreased intrathecal immunoglobulin production. This is the first report of the use of EBV-specific adoptive immunotherapy to treat MS or any other autoimmune disease.

Permission to repost

Eco
 
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NK17

Senior Member
Messages
592
EBV as Infectious Mononucleosis is what started my fall into ME/Cfs, this was in 1981 ...

My then doctor (an infectious disease specialist) diagnosed me, too bad he didn't stress how much REST and upping my Vit D3 intake would have helped my immune system to get back on track ;(.

I'm a strong believer in the EBV role as trigger/initiator and/or perpetrator of ME.

Other viruses have also a role in the pathophysiology of many neuroimmune diseases.

HHV6 is a strong candidate as well, it's capable of transactivating HERV and help his family buddies (HS1, HS2, VZV, CMV).

There might be an orchestra director among them, or they simply take turns, at the expenses of our bodies, but without "killing" us. Or if they do kill us, they do it stealthily and slowly.
 
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NK17

Senior Member
Messages
592
What was the actual treatment?
No treatment at all.
I must say that I doubt there was any anti-viral on the market in '81 specific for EBV.

There is one now valomaciclovir (Ephiphany Bioscience is the pharma company) and if I remember correctly it's in a Phase III clinical study.
It's for shingles/herpes zoster due to VZV/chickenpox and IMono due to EBV.
 

NK17

Senior Member
Messages
592
Sorry, I meant the treatment described in the MS article.
Got you ;).

From my very basic understanding they used adoptive immunotherapy.

The therapy is done by extracting ex vivo the patient's EBV specific CD8+ T cells and before reinfusing them supercharging them to kill latent viral proteins.

Basically boosting the specific killing power of specific T cells against, in this specific study, EBV latent viral proteins.

This is only done on a research level, there is no approved adoptive T cell therapy as yet.
 
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heapsreal

iherb 10% discount code OPA989,
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australia (brisbane)
Well I could do with supercharged cd8 cells. If they can do it with cd8 I wonder if this can be done with nk cells??

I hope these australian researchers are in contact with griffith uni as their research showed us mecfsers have not only low nk function but also cd8 function.
 

Christopher

Senior Member
Messages
576
Location
Pennsylvania
Well I could do with supercharged cd8 cells. If they can do it with cd8 I wonder if this can be done with nk cells??

I hope these australian researchers are in contact with griffith uni as their research showed us mecfsers have not only low nk function but also cd8 function.

I shot a short email along with a link to the full study to Stanford and the CFI - hopefully someone will take a look at it.

Here's a link to the study if you want to send it to anyone:
http://msj.sagepub.com/content/early/2014/02/03/1352458514521888.full.pdf+html
 

Christopher

Senior Member
Messages
576
Location
Pennsylvania
Got you ;).

From my very basic understanding they used adoptive immunotherapy.

The therapy is done by extracting ex vivo the patient's EBV specific CD8+ T cells and before reinfusing them supercharging them to kill latent viral proteins.

Basically boosting the specific killing power of specific T cells against, in this specific study, EBV latent viral proteins.

This is only done on a research level, there is no approved adoptive T cell therapy as yet.

You could try ProBoost. It is supposed to work with T cells. I use it regularly and along with Valtrex seems to help.
 

Wally

Senior Member
Messages
1,167
No treatment at all.
I must say that I doubt there was any anti-viral on the market in '81 specific for EBV.

There is one now valomaciclovir (Ephiphany Bioscience is the pharma company) and if I remember correctly it's in a Phase III clinical study.
It's for shingles/herpes zoster due to VZV/chickenpox and IMono due to EBV.

I was not able to find any up to date information on the Ephiphany Bioscience website. It looked like the website was last updated in 2012. Do you have any other information about the company or about whether this drug has moved past Phase II of its clinical trial?

Here is a list of drugs that are being looked at for HHV-6. http://hhv-6foundation.org/clinicians/hhv-6-treatment. The drug from Chimerix is the one that looks like it has moved on to Phase III, but I think this is targeted at CMV not EBV. Not sure if they also think it will be effective for EBV.

Pretty groggy this evening, so perhaps I am missing something, but in the U.S. is there any new drug for EBV currently in the clinical trial pipeline?

Wally
 

Ecoclimber

Senior Member
Messages
1,011
I was not able to find any up to date information on the Ephiphany Bioscience website. It looked like the website was last updated in 2012. Do you have any other information about the company or about whether this drug has moved past Phase II of its clinical trial?

Here is a list of drugs that are being looked at for HHV-6. http://hhv-6foundation.org/clinicians/hhv-6-treatment. The drug from Chimerix is the one that looks like it has moved on to Phase III, but I think this is targeted at CMV not EBV. Not sure if they also think it will be effective for EBV.

Pretty groggy this evening, so perhaps I am missing something, but in the U.S. is there any new drug for EBV currently in the clinical trial pipeline?

Wally

Check out the Charcot Project an initiative to promote research and the dissemination of information around the hypothesis that multiple sclerosis is caused by a virus. It is being generously funded by anonymous donors and AIMS2CURE.

Here: http://multiple-sclerosis-research.blogspot.co.uk/p/charcot-project.html?m=1

and

Here: http://multiple-sclerosis-research.blogspot.co.uk/2013/03/research-day-talk-charcot-project.html

Eco
 

NK17

Senior Member
Messages
592
I was not able to find any up to date information on the Ephiphany Bioscience website. It looked like the website was last updated in 2012. Do you have any other information about the company or about whether this drug has moved past Phase II of its clinical trial?

Here is a list of drugs that are being looked at for HHV-6. http://hhv-6foundation.org/clinicians/hhv-6-treatment. The drug from Chimerix is the one that looks like it has moved on to Phase III, but I think this is targeted at CMV not EBV. Not sure if they also think it will be effective for EBV.

Pretty groggy this evening, so perhaps I am missing something, but in the U.S. is there any new drug for EBV currently in the clinical trial pipeline?

Wally

You are absolutely right. Valomaciclovir was only in Phase II A in 2012, don't know where they are now. I'm quite sure that Prof. Montoya and Dr. K must be in contact with pharmaceutical companies such as Ephiphany Bioscience and therefore would tell us if Valomaciclovir was part of their arsenal.

IMO the market is ready for many more antivirals against EBV. Researchers have been slow in unearthing the damages that this beta herpes virus can cause.

Sometimes it's only in clinical practice that we discover one drug it's also active against a different strand of virus. Valganciclovir is an example.

Chimerix's antivirals look promising, if you have high titers to CMV, especially brincidofovir (CMX001), the first oral nucleotide analog broad spectrum antiviral (active against CMV, AdV, BKV, HSV1/2).

Right now the only doctor that I'm aware is using the IV version of it (Cidofovir) is Dr. Peterson, again for patients with active or extremely high titters to CMV. It has to be administered intravenously and following a certain protocol in conjunction with another drug to protect the kidneys.

I don't think there is any drug specifically against EBV in the pipeline anywhere in the world :(.

I'm pretty groggy as well and all this intense posting while very exciting it is also quite tasking.
 

Wally

Senior Member
Messages
1,167
I think that Ephiphany Bioscience may have run into funding problems, but I am not positive so take this as a question more than a definitive answer. I remember that one of the small biotech companies in the Bay Area was doing work related to EBV and this was the company back in 2010 with an EBV targeted drug that I was waiting to try.. Waited and waited from 2010 thru 2012, even remember one of the new members of CFSAC was a doctor who I think was on the Board of Directors of the company. I was even more excited when I found out that he lived less than a quarter of mile from me. I imagined running into him in the grocery store and hearing that a new discovery had been made and this illness would soon be a thing of the past. Since, I hardly ever made it to the grocery store and had trouble remembering where my car keys were, I think my dream was more of a hallucination. :ill: The rest is a bit fuzzy in my memory banks, but it seemed like waiting for this new EBV drug was never going to materialize.

As to Vistide, it is a drug that Dr Kogelnik has offered up for me to try, so I believe he is using it in his practice. I am in a holding pattern as to which treatment I will try next. Perhaps I will write about my experience with anti-virals to knock down my EBV virus (or whatever other unknown pathogens are lurking inside of me). I didn't want to write about my experience until enough time had passed for me to evaluate how my own personal trial had evolved. Perhaps, as another year has passed, it might be the right time to share my experience and have it added to the collective pot of information we patients share among ourselves. Sure that if we look hard and long enough, we will begin to see patterns and answers reveal themselves.
 
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Wally

Senior Member
Messages
1,167
Check out the Charcot Project an initiative to promote research and the dissemination of information around the hypothesis that multiple sclerosis is caused by a virus. It is being generously funded by anonymous donors and AIMS2CURE.

Here: http://multiple-sclerosis-research.blogspot.co.uk/p/charcot-project.html?m=1

and

Here: http://multiple-sclerosis-research.blogspot.co.uk/2013/03/research-day-talk-charcot-project.html

Eco

Eco,

I had been following this research, I can't remember when I stumbled upon it. But I was surprised that more people were not talking about it. It was something that Rich V. and I discussed before he passed. Kind of forgot about it over the last year, so thanks for bringing it back on to my "things to keep an eye out for" list. The list is quite long and it often goes missing, but it does always seem to eventually resurface. o_O

Wally :nerd:
 

NK17

Senior Member
Messages
592
I think that Ephiphany Bioscience may have run into funding problems, but I am not positive so take this as a question more than a definitive answer. I remember that one of the small biotech companies in the Bay Area was doing work related to EBV and this was the company back in 2010 with an EBV targeted drug that I was waiting to try.. Waited and waited from 2010 thru 2012, even remember one of the new members of CFSAC was a doctor who I think was on the Board of Directors of the company. I was even more excited when I found out that he lived less than a quarter of mile from me. I imagined running into him in the grocery store and hearing that a new discovery had been made and this illness would soon be a thing of the past. Since, I hardly ever made it to the grocery store and had trouble remembering where my car keys were, I think my dream was more of a hallucination. :ill: The rest is a bit fuzzy in my memory banks, but it seemed like waiting for this new EBV drug was never going to materialize.

As to Vistide, it is a drug that Dr Kogelnik has offered up for me to try, so I believe he is using it in his practice. I am in a holding pattern as to which treatment I will try next. Perhaps I will write about my experience with anti-virals to knock down my EBV virus (or whatever other unknown pathogens are lurking inside of me). I didn't want to write about my experience until enough time had passed for me to evaluate how my own personal trial had evolved. Perhaps, as another year has passed, it might be the right time to share my experience and have it added to the collective pot of information we patients share among ourselves. Sure that if we look hard and long enough, we will begin to see patterns and answers reveal themselves.

Funding problems are probably very common in pharmaceutical research, but for us and our disease are probably the rule, even more so now that there is very little money invested in R & D.
I absolutely relate and feel for you, because I am too worsening and have become housebound and I can imagine your disappointment and how much you wanted to bump into the doctor and hear some good news.
Being that there are so few doctors that take care of us, living close to one of them seems like a real dream come true.

Although we suffer from the same disease I know that we are all very different, that we don't harbor the exact same quantity and type of pathogens and also that the immune system functions in a very complex and dynamic way, there are too many variables and too many pathways and so much that we don't know and a lot that we think we know, so although I think it is very important and comforting that we exchange here on PR, we still have to make decisions based on some leap of faith, together with our doctors … Educated guess it's what we can call it...

I'm about to start a course of treatment with Valcyte. It has been a very long and bumpy road to get some. I hope to be able to share and report on the journey and I'd love to hear from you and about your experiences :hug:
We are in this together and the more we share the more as you justly said we'll see patterns and find answers.
 
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Martial

Senior Member
Messages
1,409
Location
Ventura, CA
What is it about EBV that triggers M.E. and CFS for some, while many other remain with antibodies from previous infection in life and never get severely sick? The same goes for other viral issues as well...

Is there a certain pre disposed factor? certain genetic reasons, or an auto immune response?
 

Christopher

Senior Member
Messages
576
Location
Pennsylvania
I've gotten acknowledgement about the paper from Dr. Ascherio, who is affiliated with the CFI Initiative.

http://cfinitiative.org/lead-researchers/alberto-ascherio/

Among the most significant research findings of his work are the identification of the Epstein-Barr virus as an etiological factor in multiple sclerosis, the findings that high levels of vitamin D may reduce multiple sclerosis risk, whereas cigarette smoking may increase risk, and the observations that caffeine, ibuprofen and high levels of blood urate are negative risk factors for Parkinson disease.
 

Christopher

Senior Member
Messages
576
Location
Pennsylvania
Check out the Charcot Project an initiative to promote research and the dissemination of information around the hypothesis that multiple sclerosis is caused by a virus. It is being generously funded by anonymous donors and AIMS2CURE.

Here: http://multiple-sclerosis-research.blogspot.co.uk/p/charcot-project.html?m=1

and

Here: http://multiple-sclerosis-research.blogspot.co.uk/2013/03/research-day-talk-charcot-project.html

Eco

The Charcot Project is an example of something we should be following and supporting as much as our own research - one will certainly benefit the other.
 

Christopher

Senior Member
Messages
576
Location
Pennsylvania
Eco,

I had been following this research, I can't remember when I stumbled upon it. But I was surprised that more people were not talking about it. It was something that Rich V. and I discussed before he passed. Kind of forgot about it over the last year, so thanks for bringing it back on to my "things to keep an eye out for" list. The list is quite long and it often goes missing, but it does always seem to eventually resurface. o_O

Wally :nerd:

I'm compiling a list of such projects here
 

NK17

Senior Member
Messages
592
I've gotten acknowledgement about the paper from Dr. Ascherio, who is affiliated with the CFI Initiative.

http://cfinitiative.org/lead-researchers/alberto-ascherio/
I've gotten acknowledgement about the paper from Dr. Ascherio, who is affiliated with the CFI Initiative.

http://cfinitiative.org/lead-researchers/alberto-ascherio/
Excellent Christopher!!!
I had my eyes on Dr. Ascherio's work as a top notch epidemiologist @ Harvard.
He has done some great work on MS.
I was very excited when I learned that he was part of the CFI initiative.

I think we should start an appllication MAP to visually keep track of all the important projects that are going on in the US and the rest of the world on ME/CFS.