Article: Dr. Mikovits Talks! The XMRV Santa Rosa Lecture: Part II by Lannie

You can view the page at http://forums.aboutmecfs.org/content.php?337-Dr.-Mikovits-Talk!-The-XMRV-CFS-Santa-Rosa-Lecture-Part-II-by-Lannie

 

Hi Rich,

Thanks for all the info about where to get sublingual B12. I think I might start off with just the sub. methylcobalamin and methylfolate and then see how i go before adding others in.

Thanks for pointing me in the right direction.

Jake

Hi, Jake.

Metafolin is available in the UK from http://bigvits.co.uk/product.asp?pid=229&cid=&tid=&bid=27 This is a Solgar product, and it is the genuine Merck material.

Sublingual methylcobalamin in 1,000 microgram sublingual chunks is available in the UK from

http://www.solgar.co.uk/modules/catbuild/files/Methylcobalamin1000mcg30NuggetsE1950.htm This is also a Solgar product.

Dr. Myhill is not giving B12 or magnesium injections at the moment, pending her hearing in High Court to try to lift the restrictions placed on her practice by the GMC. But sublingual works O.K.

Yes, a multivitamin, multimineral with substantial but safe dosages of the essential nutrients (not RDA levels) is important.

Supplying amino acids can also be important, particularly methionine, serine, cysteine and glycine.

Support for the lipid membranes is important, too. The simplified protocol uses a phosphatidyl serine complex, which contains a range of phospholipids. This is also available in the UK from Solgar: http://www.solgar.co.uk/modules/catbuild/files/PhosphatidylSerineComplex500mg30TabletsE2803.htm

I hope this helps. It's important to be working with a physician while on this type of treatment, because a small number of people have reported serious adverse effects while on it.

Best regards,

Rich

 

rich and kyle,

thanks for the great info. So would i need to get a prescription for Metafolin from my doctor - as it seems to be a medicinal food. I will try and get a script tommorow. I can't seem to find any decent suppliers online for the UK.

So if I take Metafolin and Klye might I ask where you get the methylcobalamin b12 injects from? do you know if sarah myhill is back on the scene and able to supply them again? i used to get some b12 injects from her but i just realised its the rather dodged cynaocobalamin (cyanide bonded?)

So ideally if i start with: Metafolin, methylcobalamin (injection), high dose quality vitamin, amino acid mix tablets.

Do you think this is the best way to start rich?, I would like to give this another shot if I have been taking suboptimal type of folic acid.

My biggest problem is getting methylcobalamin injections i need to find a source!! arghhh

Kyle its great to hear you have had such a great improvement, I hope I am able to replicate some of your success.

Rich thanks for sharing all your knowledge with others, I want to give this another shot!

Thanks,

Jake

I know that in Mandimart.co.uk, they sell the Folapro and the Actifolate from the Konynenburg protocol.

 

This reads like a contradiction - either the positive/negative results are clear and reliable, or they are not. I don't understand how it can be both. Can anyone help me out?

Hi jspotila, I have been trying to come to grips with this question since 2009, and have posted several times on it - she is confident that the percentage of negatives isn't very high I think, but even one false negative is bad news for a patient who wants to be treated. The scary implication from this is that the population prevalence will go up from 4-6 percent. I am still betting on over 10%, and thats a lot of people.

This is an issue about individuals versus populations. 6% isn't hugely different from 4% (percentage-wise, yes, but still basically a single digit figure). However, if you test negative, its a zero versus "100%", a Zero-One result. Its important to remember also that much of the testing used, and probably all the public tests, can't detect the second virus either.

Once we get prevalence figures from larger cohorts of neuro-immune patients then we can add these groups to the healthy population, and get ever closer to my predicted ten percent.

Bye
Alex

 

Yes, I am very happy to see these things coming together!

Hi Rich, in my opinion when the science starts dovetailing together like this its a very good sign. It might mean we are close to a unified theory of ME/CFS, and once we have that we will finally understand where all the pieces everyone has been working on will fit.

This is a good turn of events, it will be better if clinical trials can start and show these treatments can work synergistically.

Bye,
Alex

 

With regard to the situation of getting positives via culture and not via serology, remember that the BWG considers culture the gold standard. They can grow out a detectable amount from very low copy numbers. A serology test doesn't have that advantage.

Until we know where the reservoirs are and can (hopefully) directly test them we are going to be frustrated by blood tests until we can find faster and easier ways to find this sucker.

I'm encouraged by the plans to do large scale testing on the blood supply/donors, but we need them using valid tests.

 

Mark, many thanks for what looks to me like an excellent summary of where we are--and with clues as to where we hope we will go, led by Judy and her great team. There is hope in the air! Best, Chris

 

The Cleveland Clinic tested 11 patient samples, but I don't recall any reference to them receiving any controls. It's not explicit in the paragraph you quote that CC was blinded to the CFS status of those 11 samples, although they certainly could have been.

The paragraph you quote says NCI received 100 samples, but the Virulence 2010 paper says 48 patient samples were sent to NCI. I don't recall any reference to NCI receiving additional patient or control samples, so the 100 number confuses me. The Virulence paper also says those 48 samples were collected by the Sierra Internal Medicine practice and sent to NCI. Is it possible that someone at NCI (who not a lab worker who performed the PCR) knew the patient status of samples? For example, Maureen Hanson was unblinded to the CFS status of her patient/control samples so she could present results but her lab workers are still blinded.



I just reread a couple of these papers yesterday so certain points are fresh in my mind. I find it very easy to get confused about sample numbers, tests run, etc. and I've paid closer attention than many patients I know. I think misunderstandings and misrememberings are quite possible without them being deliberate attempts to sow confusion and doubt.

a) you've read what "asleep" quoted. "All samples were blinded, as mandated by the NCI and WPI institutional review board approvals. All experimental procedures were done by the same personnel, in the same physical laboratory space, under identical protocols.". No room for questions here. All samples were handled the same way. Cort, I do remember that Dr. Mikovits said they had to check samples taken at different times - but who said they didn't do so for healthy controls too? Not to mention that it would still not explain the difference. Including the difference between 9/18 patients positive for antibodies while none of the 16 healthy controls were positive for antibodies.
b) jspotial, you say:

The paragraph you quote says NCI received 100 samples, but the Virulence 2010 paper says 48 patient samples were sent to NCI. I don't recall any reference to NCI receiving additional patient or control samples, so the 100 number confuses me.

"asleep" quoted the following sentence:

Investigators at NCI received 100 samples from individuals without knowing their health status

I think that you've answered your own question when you said "48 patient samples were sent to NCI", but the number of all of the samples sent to the NCI was 100. So - 52 of those samples were from healthy controls (which fits, because the WPI had more healthy controls in their study than ME patients). And none of the laboratory workers - not at the WPI and not at the NCI - knew about the health status of the individuals.

Yes, it's easy to get confused. But before spreading misleading thoughts, espeically when these are negative thoughts which would get it more difficult to find that XMRV is the cause of ME if it is the cause, more cautious needs to be taken. Moreover, you have the number one source for answer very avaiable for you: Dr. Mikovits answers emails very frequently, sometimes within minutes from recieving them. Why won't you ask her before throwing a misleading and counter-productive arguments into the world wide web?

 

Thanks. Cort! Interesting rading.

 

Yes, it's easy to get confused. But before spreading misleading thoughts, espeically when these are negative thoughts which would get it more difficult to find that XMRV is the cause of ME if it is the cause, more cautious needs to be taken. Moreover, you have the number one source for answer very avaiable for you: Dr. Mikovits answers emails very frequently, sometimes within minutes from recieving them. Why won't you ask her before throwing a misleading and counter-productive arguments into the world wide web?

Respectfully, I am not "spreading misleading thoughts" nor am I "throwing a misleading and counter-productive arguments into the world wide web." I am asking a few questions to try and clear up my confusion. Big difference, and since I have not accused anyone of anything, I would appreciate the same courtesy in reply.

 

Cort,

This is a very confusing statement, which seems meant to imply serious, biased flaws to the WPI's work.

Their work, a joint effort with the National Cancer Institute, and the Cleveland clinic, for this study, was Peer Reviewed for over 6 months,and then published by the one of the World's top 2 Scientific Journals.

Please clarify your comments: What "researchers" are you referring to, exactly what did they say, and based on what?

Please provide quotes, and clearly distinguish between them and your paraphrasing.

Thank you,

Katrina

Sorry Katrina, I don't have direct quotes. My understanding was that it was known that the WPI had to at times look at several samples or several samples from the same patients to find the virus. My memory is that Dr. Mikovits said that after the Science paper and indeed that is what the section from March I printed from that paper stated....in that section I suggested that meant the virus is harder to find than the 67% positive rate in the paper suggested -which appears to be true - both from the papers and from the BWG findings.

Remember this is all about straight PCR - not culturing. Judging from the BWG findings the WPI is not able to get consistent results from PCR but is able to get them using culturing. My recollection from the BWG meeting is that Dr. Mikovits said that they don't even really do straight PCR anymore - all they do is culture - which was why the results were variable. (Which does in itself suggest that they probably did do multiple tests on some samples for the Science paper...otherwise how would they get such a high positive rate?).

To some extent this is a moot point. If it was true that they simply didn't look as hard for the virus in the controls that could suggest that the positive rate in healthy controls might be much higher than was reported. That hasn't happened in the positive studies and, of course, the negative studies aren't finding anything. Nobody is really worried about getting the positive rate wrong; the big problem now is having labs find the virus.

It occurred to me that Dr. Mikovits statement that 'the politics will be over soon' might be connected to her statement, in her last two lectures, that the disparate results are due to refreezing samples more than once. If that's the case this whole issue should be cleared up quickly and soon. Each of the four BWG labs should be able to easily assess this and hopefully we'll have an announcement. Wouldn't that be something!

 

But before spreading misleading thoughts, espeically when these are negative thoughts which would get it more difficult to find that XMRV is the cause of ME if it is the cause, more cautious needs to be taken.

I know this is a touchy issue - believe me I know but I don't think we should need to worry about whether how we discuss will somehow impact researchers ability to determine if XMRV is the cause. Research Institutions have their own means (multiple committee panels) for determining which research to fund. I could see our discussions impacting the WPI''s ability to do research if they turned off some large donors from contributing which is possible but I don't know if its very likely.

I think we and I need to be very careful because alot of peoples hopes are riding on XMRV. On the other we want to look at it as clearly as possible - which is not easy given how complicated this all is. I have been clear that I swing back and forth all the time. I think both sides have really good arguments actually.

I agree with Jennie that what we need is data, data, data......and data, unfortunately, has been hard to come by lately. Other than the Huber study have we had a new study since Alter/Lo? Its been quite a while - or at least it like it seems like it has.

 

Until we know where the reservoirs are and can (hopefully) directly test them we are going to be frustrated by blood tests until we can find faster and easier ways to find this sucker.

I'm encouraged by the plans to do large scale testing on the blood supply/donors, but we need them using valid tests.

Agree.

We are not really going anywhere until there is a reliable accepted test for both the presence of the virus and the quantity of virus (viral load). That is the top priority for now, IMHO.

 

XMRV is in a strange place...it is so enticing on so many levels....it's just got to get over the hump. I wonder what's happening with the Alberta study....they got going in Sept of last year - they said they were collaborating with the WPI - they have a nice new facility...we didn't hear anything from them at the Workshop - that is an important study that I completely missed until last week.

I wonder what's going on with them. They thought they would get done pretty quickly

Dr. Houghton has been in touch with Dr. Mikovits at the Whittemore Peterson Institute and other experts in the field to ensure that the methodology of the study will be adequate to detect the virus if present.

We have an ambitious time line. The study will go before the U of Alberta ethics committee on July 23. If approved we want to have blood samples collected and analyzed by August 30th so that we are in a position to use whatever information we find to apply for a bigger grant to do more detailed research. The grant application deadline is September 15th, 2010.

Our protocol includes an assistant who will go to the participant's home or work (or some other location if preferred) to draw the blood. We hope this will allow the severely ill to participate as the blood can be drawn from the bedside if necessary.

We are looking for 50 subjects with ME/CFS (meeting Canadian Consensus Criteria) and 50 healthy people matched by age and gender.

This was in Sept Calgary Sun - so maybe it took them a while to get started

From Calgary Sun

Alberta researchers hoping to prove once and for all a debilitating syndrome is viral in origin are launching an ambitious study in Calgary and Edmonton.

Outbreaks of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have been documented since 1930, but have no known cause or accepted diagnostic tests.

Recent research has argued both for and against the theory that ME/CFS, which causes exhaustion, sleep disorders, cognitive problems, and muscle and joint pain, is linked to a retrovirus called XMRV, a relative of HIV.

Dr. Eleanor Stein, a Calgary ME/CFS specialist and researcher, said a study launching in Calgary will look to confirm if the syndrome is in fact linked with the retrovirus, which is tricky to find and treat.

The retrovirus actually fits itself into our own DNA so that when our DNA replicates, the retrovirus replicates with it, she said.

There is no known treatment for ME/CFS and it is estimated more than 300,000 Canadians may be affected.

Stein will be joined by Dr. Lorne Tyrrell, founding director of the Li Ka Shing Institute of Virology in Edmonton, and Dr. Michael Houghton of the University of Alberta, who holds the Canada Excellence Research Chair in Virology, for a preliminary study next month.

Approximately 100 participants 50 diagnosed with ME/CFS and 50 healthy are needed between Calgary and Edmonton.

The subjects will answer questionnaires and have blood drawn ideally by the end of September, said Stein, so the research team has enough time to gather data and apply for grants early next year to fund a larger study.

Patients severely affected by ME/CFS are invited to join the study as well, as the team can draw blood at their residences.

Interested Calgarians are asked to call 403-287-9941 and Edmontonians 780-492-8415.

jenna.mcmurray@sunmedia.ca

 

Maybe Lannie or Cort can help me understand this. If WPI cannot confirm a sample is truly negative, then the Blood Working Group study is completely useless. But on the other hand, Dr. Mikovits seems to be completely confident in the negative results of testing of healthy people. This reads like a contradiction - either the positive/negative results are clear and reliable, or they are not. I don't understand how it can be both. Can anyone help me out?

In addition to Mark's informative and valuable remarks on statistical data vs individual data points, I want to point out the "you can't prove a negative" concept. I think Dr M is using this concept in her remarks about individual negative tests.

An illustrative example: I can walk in the nearby woods all day, every day for 5 years and never see a fox. Does that mean there are no foxes in the woods? No. It could be that there are no foxes. It could also be that I am not looking in the right way for foxes, or at the right time for foxes. Not finding foxes doesn't mean no foxes are there.

On the other hand, if I see a fox during my walks, I know that there is at least one fox there. Without question. It's there. That's no guarantee there are many foxes, but there is at least one fox for certain.

So, if I look for XMRV and find it, I know it's there. I've seen it. If I look and don't find it, it could be that there is no XMRV there, or it could be it's the wrong time, or way, to find XMRV.

Including Mark's point about statistical data vs individual data, if I look for squirrels in 100 shopping malls and 100 woods and find only 1 squirrel altogether in the shopping malls and at least one squirrel in 90% of the woods, I can safely conclude that is extremely unlikely that there are squirrels in shopping malls and extremely likely that there are squirrels in woods.

However, that does not mean I will never find a squirrel in a shopping mall. Nor does it mean that I will always find squirrels in the woods. Maybe some woods don't have squirrels, or maybe I just didn't see them. Any given shopping mall or woods can give an anomalous result.

One (or a few) false positive doesn't disprove the theory. It does suggest, though, that any one test could be a false positive. That's true of every medical test we take. A number of false negatives doesn't disprove the theory, either. They could simply mean the test isn't good enough to find all the cases.

If I had an XMRV test and it came back positive, I'd be 99% confident I was XMRV+ because they actually "saw" something. If my XMRV test came back negative at this point all I could conclude was that they didn't find it, not that it wasn't there. If I was healthy (shopping mall), I would conclude that the odds were very much in favor of my actually being XMRV-, but not certain. If I was unhealthy (woods), the odds would appear to be in favor of them not finding it rather than it not being there, and I might consider testing again at some future time. Still, no guarantees.

I don't understand this either. Is Dr. Mikovits saying that patients cannot make antibodies to XMRV only? Or that a severely ill patient cannot make antibodies to lots of pathogens? The latter would suggest an AIDS-like presentation with the immune system completely unable to do its job. I know we have lots of co-infections, but that's different from an immune system unable to function by making antibodies. If Dr. Mikovits is saying patients can't make antibodies to XMRV alone, why would that be? Do they understand the mechanism for why the immune system would be unable to mount a response to one pathogen but not others?

I wonder if this is a stage-of-disease issue. My reading (and it could easily be wrong) was that she was suggesting that the most ill patients might not be able to mount an antibody response, not that every patient may not be able to.

My personal experience was that in the earlier stages of ME/CFS my immune system seems revved up. As I became sicker, my over-active immune system symptoms decreased and I started catching everything that came near me. And at least one latent infection reactivated. I think other people have seen this pattern.

Perhaps the sickest patients can't produce antibodies in sufficient amounts (or sufficiently functional), but not to the degree seen in AIDS. This is seen in HIV patients -- a progression of immune system collapse. Maybe our immune system can become very weak, but not completely shot. Maybe the antibodies are there but in small numbers, or malformed so that they are poorly functional and perhaps not detectable by known methods.

Less sick patients may still be able to produce antibodies to different degrees. They appear to be likely to test positive on antibodies tests. By that theory, if you're in the hyped-up immune stage you might be more likely to test postive on the antibody test than someone who is sicker. Not a surety, just a thought....

 

But it's an interesting question - "why the immune system would be unable to mount a response to one pathogen but not others?" - so I've pondered it and come up with a hypothesis...

Hi Mark, I would like to add another possible hypothesis to the three you listed. XMRV might more actively aggressively infect immune cells, including the B cells needed for antibody production. So, which virus is always there to be attacked and always stimulating B cells to attack it? XMRV. XMRV might therefore destroy the immune cells that are chronically activated, resulting in deletions in these B cells subsets, and a loss of antibody immunity to all chronic infections, but not transient ones. I am still thinking about possible mechanisms that would allow this hypothesis, as there are problems with it too.

bye
Alex

 

IrsiCaixa has found the same reduction in CD57 (NKCells activity) as Dr. Judy Micovits described in this Lecture.

Important independent confirmation.

Please support the Spanish CFS Liga :Sign Help: http://forums.aboutmecfs.org/showth...CFS-Liga-needs-our-help-please-sign-petition-!!!!

 

Rich and Cort,

What great info! The comments string to this post was amazing.
I spent about an hour reading the references about "Augmenting Glutathione in CFS Patients" and was fascinated - it all made sense to me. Before starting Ampligen I was getting Glutathione shots I.M. for a few months, and prior to that I drank that whey protein drink religiously. Then I heard Cheney do a 180 degree turn on the whey protein and glutathione supplementation, contradicting everything he'd said for years when he was promoting the whey powder, (and some say earning six figures doing it) and I ended up totally confused. I got a few laughs about it in my blog post some months back entitled "The Ampligen Supremacy", where I described how foolish I felt mixing up little batches of "Imuplus" for years, spraying powder and this wallpaper glue type substance all over the kitchen, only to hear Cheney years later advise against it, saying essentially it was bad for us.

Can you help me understand where the disconnect is? I always seemed to feel better with Glutathione injections, but Cheney's comments against it have me wondering. Thanks!

 

Rich and Cort,

What great info! The comments string to this post was amazing.
I spent about an hour reading the references about "Augmenting Glutathione in CFS Patients" and was fascinated - it all made sense to me. Before starting Ampligen I was getting Glutathione shots I.M. for a few months, and prior to that I drank that whey protein drink religiously. Then I heard Cheney do a 180 degree turn on the whey protein and glutathione supplementation, contradicting everything he'd said for years when he was promoting the whey powder, (and some say earning six figures doing it) and I ended up totally confused. I got a few laughs about it in my blog post some months back entitled "The Ampligen Supremacy", where I described how foolish I felt mixing up little batches of "Imuplus" for years, spraying powder and this wallpaper glue type substance all over the kitchen, only to hear Cheney years later advise against it, saying essentially it was bad for us.

Can you help me understand where the disconnect is? I always seemed to feel better with Glutathione injections, but Cheney's comments against it have me wondering. Thanks!

Hi, Kelvin.

I'm familiar with the history you described. I first heard about glutathione from Dr. Cheney in 1999. For five years, like Dr. Cheney, I encouraged PWCs to try to build up their glutathione by a variety of means. That's when I compiled the article about augmenting glutathione. This did help some PWCs to feel better. However, I found that this did not produce a permanent benefit. When people stopped, the benefit went away. I began to suspect that there was a vicious circle holding glutathione down, and I reported this in a poster paper at the 2004 AACFS conference. Shortly after that, S. Jill James et al. published a paper in autism research that showed that glutathione is also low in autism, and that this is coupled with a partial block in the methylation cycle, which is upstream of glutathione synthesis in the sulfur metabolism. They found that treating to lift this partial block caused glutathione to come up automatically. This was an "Aha!" moment for me, because I could see the similarities in the biochemistry of autism and CFS. I therefore stopped encouraging people to try to build glutathione directly, and instead to treat to lift the partial methylation cycle block. This turned out to work, as shown by lab testing in a clinical study that was carried out by Neil Nathan, M.D., and myself. You can read about this at www.cfsresearch.org

In the meantime, Dr. Cheney also stopped recommending direct supplementation to build glutathione. He got some lab data that I think was misleading, indicating that glutathione was not actually depleted. I've discussed this with him, but have not been able to convince him that glutathione is indeed depleted. I think his view is that it is just not being recycled properly by the glutathione reductase reaction. In any case, he is not recommending the direct building of glutathione any longer.

I have recently suggested that using liposomal glutathione might help to relieve the excitotoxicity that some people experience on the methylation treatment, but have not received feedback on this, so don't know if it will actually work.

I might note that "Freddd" on this forum reports that supplementing glutathione together with his methylation protocol was disastrous for him. I have suggested a possible reason for that today on the glutathione thread.

Anyway, this continues to be an active issue, and Dr. Mikovits's mention of glutathione in her talk earlier this week will no doubt raise the interest in this again.

Best regards,

Rich

 

Hi, energyoverload.

I'm sorry to hear that the methylation treatment you tried did not bring you more benefit. Perhaps using Metafolin (methylfolate) rather than folinic acid would be more helpful. It is available in the UK. Some people have difficulty converting folinic acid into methylfolate for genetic reasons. Other issues that can limit the effectiveness of methylation treatment are deficiencies in amino acids which are needed to feed the methylation cycle and related pathways, and deficiencies in the vitamin and/or mineral cofactors for this part of the metabolism. HPU/KPU is another possibility, since it depletes B6, zinc, manganese, biotin and other nutrients. Also, people who have Lyme disease or mold illness appear to need separate treatments for these in addition to the methylation treatment.

I was not present at Dr. Mikovits's talk, so I don't know exactly what she said, but my impression from the reports as well as from speaking with her a couple of times in the past is that she is suggesting that combining treatments may help. I don't think there is much experience with this yet. I think she is projecting from the genetics and biochemistry, as I am also trying to do.

I'm sorry that all of this has not yet been worked out and tested. All we can do is to start from where we are. I know it's frustrating.

Best regards,

Rich

Rich. Can't wait to see the day when you get some real research dollars and are able to accurately personalize treatments for sick folks. Thanks for all your hard work.

You mention that lyme folks need "seperate treatments". Can you say what those "seperate treatments" might be?

Thanks!
Mark