EBV targeting treatment yields clinical improvements in spms

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EBV targeting treatment yields clinical improvements in spms

Postby Anonymoose » Sat Nov 09, 2013 6:56 pm

Treatment of secondary progressive multiple sclerosis by boosting CD8 T cell immunity to Epstein-Barr virus using a novel adoptive immunotherapy
http://registration.akm.ch/einsicht.php ... KEN_ID=900

N=1 and only 10 weeks but still...
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Re: EBV targeting treatment yields clinical improvements in

Postby Anonymoose » Tue Feb 04, 2014 6:33 am

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Re: EBV targeting treatment yields clinical improvements in

Postby cheerleader » Tue Feb 04, 2014 10:26 am

One patient is treated, a 42 year old man who has had MS since 1992, called RRMS until 2004---he is now called SPMS,
However, the clinical marker they use for improvement after treatment is reduction of gadolinium enhancing lesions, and his CSF IgG markers are down.
Aren't enhancing lesions part of RRMS, not SPMS?
I'm incredibly happy for this one patient...he is doing better, and that is a good thing!
But isn't qualifying this treatment as helpful for "progressive MS" misleading? There is no mention of gray matter atrophy.
Anybody else?
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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: EBV targeting treatment yields clinical improvements in

Postby Anonymoose » Wed Feb 05, 2014 5:59 am

SPMS follows RRMS. It seems likely that if ebv contributes to rrms, it also contributes to spms. I'm not sure getting all micro-analytical about the differences between the two phases is relevant in this case.

You gotta admit it's pretty cool that a T cell that specifically targets just one virus led to clinical improvement. Definitely a step forward for some of us. :)
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THE BLACK SWAN ATTACKS AGAIN?

Postby ton » Wed Feb 05, 2014 6:39 am

THE BLACK SWAN ATTACKS AGAIN?

Immunotherapy against EBV
Posted by Gavin Giovannoni at 08:30 #msblog #msresearch
Targeting EBV infected cells using immunotherapy. Is this the future of MS treatment?


"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 active 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 ...

Image
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.
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Re: EBV targeting treatment yields clinical improvements in

Postby dlynn » Wed Feb 05, 2014 8:14 am

cheerleader,
I agree with you re. GMA and enhancing lesions. Did you mention something about your husbands' many lesions
but a reversal of GMA. (after CCSVI procedure)?
And doesn't ldn have the same effect, boosting T-cells, as in Drs Bihari and Zagons' research?
If that's the case, ldn seems so much simpler (than in-vitro stimulation) and for me it works great (until I get another procedure).
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Re: EBV targeting treatment yields clinical improvements in

Postby cheerleader » Wed Feb 05, 2014 10:09 am

dlynn wrote:cheerleader,
I agree with you re. GMA and enhancing lesions. Did you mention something about your husbands' many lesions
but a reversal of GMA. (after CCSVI procedure)?
And doesn't ldn have the same effect, boosting T-cells, as in Drs Bihari and Zagons' research?
If that's the case, ldn seems so much simpler (than in-vitro stimulation) and for me it works great (until I get another procedure).


dlynn--I guess my main concern with this study --in one person with SPMS-- is that they used a questionable bio-marker to measure success. Enhancing lesions are not associated with SPMS, but rather RRMS. And recent research is looking at brain atrophy as a more reliable marker of MS entering the progressive phase. Which they did not monitor.
http://researchonline.lshtm.ac.uk/2934/
http://brain.oxfordjournals.org/content ... 9.abstract
http://www.ajnr.org/content/26/2/341.full

But listen--if this treatment helps people, that's a wonderful thing!! Yes, Jeff had a reversal of gray matter atrophy after his treatment. His third ventricle, brain stem and thalamus are all "normal" now. He's had no further lesions. I'm not sure about LDN, but that may be, as well. This research certainly turns how we currently treat MS--with CNS immune system depleting medications--on it's head!! And wow--that's a TON of hyperbole from Dr. Giovannoni :confused:
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: EBV targeting treatment yields clinical improvements in

Postby Anonymoose » Wed Feb 12, 2014 7:44 am

They are making ebv targeting T cells in the US (NY) too...for cancer. I wonder if they might be open to sharing with msers. I can't pursue that route right now but would love to hear if anyone else has success.

http://maxcurefoundation.org/celltherapylab/

http://www.mskcc.org/cancer-care/doctor ... d-o-reilly
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Re: EBV targeting treatment yields clinical improvements in

Postby centenarian100 » Wed Feb 12, 2014 8:07 pm

Anonymoose wrote:Treatment of secondary progressive multiple sclerosis by boosting CD8 T cell immunity to Epstein-Barr virus using a novel adoptive immunotherapy
http://registration.akm.ch/einsicht.php ... KEN_ID=900

N=1 and only 10 weeks but still...


this is an interesting article.

It is mentioned in mousedoctor's website here:

http://multiple-sclerosis-research.blog ... ender.html

It is well known that anti-b cell therapy is very effective in relapsing multiple sclerosis (rituximab/ocrelizumab/ofatumumab). There is some speculation that the efficacy of these drugs could be related to the indirect antiviral properties (depleting the CD 20+ cells which host epstein barr virus) rather than the immunological effects.

This is a speculative but highly interesting idea.

I'm not impressed by the case report, but I would like to see a small randomized controlled trial. Rituxan has been studied in SPMS with possible benefits in younger patients (< 50), those with relapses, and those with gadolinium enhancing lesions (sorry, I don't remember the source-but trust me there is a high quality RCT which has this post-hoc data)

-C
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Re: EBV targeting treatment yields clinical improvements in

Postby Anonymoose » Wed Feb 12, 2014 8:31 pm

Hi Cent,

I've been rituxan'd to the gills and expect it to only give me a short term break at this point. If ebv is causing the immune cascade, the ebv immortalized plasma and epithelial cells will surely re-infect the new B cells in good time. :( ...unless ebv specific cd8+ T cells miraculously normalize. Maybe it'll happen with less stress. <shrug>

You aren't impressed by the lower csf iGg numbers? I am!! And as for ms treatment options, I'm not sure you could get less harmless than the trained super T cells. They've been trialling them for cancer for several years with good success and few if any negative reactions. I think they are doing it in tx and ca as well as ny. Probably elsewhere. With nothing else to turn to (in my opinion), I think eventually, I'll try to get them.

Pender et al are gearing up for a clinical trial. They moved pretty quickly on sharing patient #1's results. I expect the trial results will be out in two years or so. :)

Cross your fingers! It can't hurt.
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Re: EBV targeting treatment yields clinical improvements in

Postby CureOrBust » Thu Feb 13, 2014 12:04 am

From my understanding, enhancing lesions on MRI are signs of inflammation. Inflammation is still a factor for SPMS. Its PPMS that I thought would be without inflammation, and therefore no enhancing lesions.

http://www.nationalmssociety.org/about-multiple-sclerosis/progressive-ms/secondary-progressive-ms/how-spms-differs-from-ppms/index.aspx
In SPMS, people may or may not continue to experience relapses (also called attacks or exacerbations) caused by inflammation;


As for using the bio-markers they did use, I think it may be wise to use the same ones used to report on other treatments ie the "industry standard" The argument if these are the best bio-markers, is a separate issue.

I followed up on this story with a little more research on the web, and found the patient treated was actually a professor, that I think worked at the same university as the research doctor. ie they either new each other or knew of each other through another contact. This fact appears to be a selectively released fact in nearly all the press releases for some reason.
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Re: EBV targeting treatment yields clinical improvements in

Postby Leonard » Thu Feb 13, 2014 12:23 am

centenarian100 wrote:
Anonymoose wrote:Treatment of secondary progressive multiple sclerosis by boosting CD8 T cell immunity to Epstein-Barr virus using a novel adoptive immunotherapy
http://registration.akm.ch/einsicht.php ... KEN_ID=900

N=1 and only 10 weeks but still...


this is an interesting article.

It is mentioned in mousedoctor's website here:

http://multiple-sclerosis-research.blog ... ender.html

It is well known that anti-b cell therapy is very effective in relapsing multiple sclerosis (rituximab/ocrelizumab/ofatumumab). There is some speculation that the efficacy of these drugs could be related to the indirect antiviral properties (depleting the CD 20+ cells which host epstein barr virus) rather than the immunological effects.

This is a speculative but highly interesting idea.

I'm not impressed by the case report, but I would like to see a small randomized controlled trial. Rituxan has been studied in SPMS with possible benefits in younger patients (< 50), those with relapses, and those with gadolinium enhancing lesions (sorry, I don't remember the source-but trust me there is a high quality RCT which has this post-hoc data)

-C


I think for progressive MS, the issue is not suppressing the B-cells but rather strengthening newly created B-cells in order that EBV is pushed back into its shelter. see for example:
http://www.hindawi.com/journals/jir/2013/535738/
http://en.wikipedia.org/wiki/B_cells#cite_note-3

I explain the success of the Wahls diet as a better nutrition (phytonutritients/antioxidants) of newly created B cells (with stronger mitochondria) and thus better functioning of these cells to get EBV pushed down. Just like the immune/B system did in the 14th century with the pest pandemic where people with a rich varied diet had much better chance of survival than those who had a very one-sided grain based diet.
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Re: EBV targeting treatment yields clinical improvements in

Postby Scott1 » Thu Feb 13, 2014 12:40 am

If the only thing you do is focus on B cells and EBV there can only be two ways of limiting the increase of the virus;1) eliminate the host (ie the B cell) or 2) put a stop in the codan of the RNA of the EBV to stop it replicating. Anything else is aimed at the product of the EBV infected B cell. At the outer edge there is the possibility of vaccine which is Penders approach.
You need a pretty potent treatment to eliminate B cells (eg Rituxan) or a very long term antiviral treatment to limit EBV as the cells divide (eg Valacyclovir). Everything else is containment until we have a vaccine.

I think there is more to it than this.

Regards
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Re: EBV targeting treatment yields clinical improvements in

Postby Leonard » Thu Feb 13, 2014 1:00 am

Scott1 wrote:If the only thing you do is focus on B cells and EBV there can only be two ways of limiting the increase of the virus;1) eliminate the host (ie the B cell) or 2) put a stop in the codan of the RNA of the EBV to stop it replicating. Anything else is aimed at the product of the EBV infected B cell. At the outer edge there is the possibility of vaccine which is Penders approach.
You need a pretty potent treatment to eliminate B cells (eg Rituxan) or a very long term antiviral treatment to limit EBV as the cells divide (eg Valacyclovir). Everything else is containment until we have a vaccine.

I think there is more to it than this.

Regards


http://www.health-matrix.net/2013/08/06 ... gus-nerve/

I think here is the key. Quote from the article:

This herpes virus varicella-zoster is a very problematic virus that contributes to mitochondrial dysfunction even in its latent infection phase. As I explained in On Viral “Junk” DNA, a DNA Enhancing Ketogenic Diet, and Cometary Kicks , most, if not all of your “junk” DNA has viral-like properties and if a pathogenic virus takes hold of our DNA or RNA, it could lead to disease or cancer.

Strong mitochondria/DNA is important for well functioning newly created B cells.
One can't get the EBV out of the cells, infection is normal for 95 % of people, but it should get back in and stay there.
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Re: EBV targeting treatment yields clinical improvements in

Postby gainsbourg » Thu Feb 13, 2014 2:02 am

I no longer post very frequently on this forum, but I was so heartened to hear of this study I felt I had to write something.

Just to remind everyone that Epstein Barr (EBV) is a form of the HERPES virus, and that other herpes strains, such as Varicella Zoster Virus (VZV) also have an association with MS.

This study provides yet more evidence that MS is caused by the presence of the herpes virus, in one or more of its various forms.

Ton says
I am a firm believer that EBV causes MS


I am delighted to see statements like this starting to appear on this forum, but I would go much further. I am certainly on record as saying that I believe MS is caused by HERPES - period.

The reason the MS culprit was missed for so long is that neither EBV, VZV or whatever herpes strain, actually "attacks" . The mere presence of the herpes virus somehow stimulates the immune system to attack the healthy tissue where the dormant herpes resides, ie. nerve tissue. The lack of "attack" evidence led researchers and clinicians to conclude herpes was not causal of MS, but was perhaps some kind of bystander. However, now these new adoptive immunotherapy drugs are being developed, treatment will soon be available in any case - and that's what really matters.

I've searched long and hard for natural anti herpes remedies for some years now. If anyone knows one please let me know!

Certain forms of venom have been shown to have anti-herpes capabilities, maybe this is why venom has also been known to help with some cases of MS.

The reason I initially became interested in the herpes/MS connection was my fascination with how stress can play a role in MS attacks, namely how frequently stressful episodes precede MS attacks. Is it coincidental that stress is also known to precede outbreaks of the herpes virus, such as the herpes simplex strain? I think not.

Here's some general research about adoptive immunotherapy (AI) and herpes. Apparently, AI may be used to combat nasopharyngeal cancer, which is thought to have an association with MS.

http://www.ncbi.nlm.nih.gov/books/NBK47440/

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