Tuesday, July 29, 2014


The following is an update on mitochondria and mitochondria testing in ME/CFS, a kind of overview as I see it. None of the following has to do with "Science", say, as practiced by Dr. Lipkin. Instead it fits more into the category of what Dr. Shoemaker would call "desperation medicine". I prefer myself to call it 19th century medicine, epitomized by this: "here, try this".

I do not pretend to be interested in science - especially relative to ME/CFS. However, real science activity in other areas - the immune system for instance, or gut ecology - is of great interest to me. I absolutely believe that something helpful will "slop over" into "my illness area" from other illnesses. This is my view and I work accordingly, trying to calculate the odds of any particular treatment, knowing that all treatments are experimental ("non-scientific") - and a potential threat. No one can convince me though that "my chronic illness" does not involve mitochondrial dysfunction.

Dr. John McLaren-Howard started Biolab in London many years ago. He has always been a real hero to me. When he retired, he formed the small lab Acumen lab in Cornwall UK. (I have always imagined Acumen to be in Dr. Howard's basement - or garage.) Dr. Howard has continued doing various tests that he began at Biolab. Principal among these is a mitochondrial profile test (examples are at the end of this post). Dr Sarah Myhill discusses the mitochondrial profile test here. Dr. McLaren-Howard offers other mitochondrial tests - translocator protein, DNA adducts, cell-free DNA, Cardiolipin studies in mitochondrial membrane, blood metallothionein studies, and toxic effects studies. All these tests give insight into the working of the mitochondria.

Dr. Howard has worked with Norman Booth and Sarah Myhill and published various papers on his mitochondrial testing, as it relates to ME/CFS patients. A 2009 paper can be found hereHere is another important paper from 2012.

I wrote about this mitochondrial test in 2011 in another post on this blog, and also here a year later.

For a fee, Dr. Myhill will write an analysis on the test result and suggest various treatments. The treatments that she suggests to increase mitochondrial function are well known and can be found here and roughly parallel what in the larger world of mitochondrial illness is known as the "mitochondria cocktail". This includes co-Q10, acetyl-l-carnitine, d-ribose, NAD, creatine, and magnesium. I think it is fair to say that great weight is put on magnesium.

Often magnesium is found to be low in ME/CFS patients and this is one element that Dr. Myhill says can be corrected through sub-Q magnesium injections. (I would appreciate hearing a conversation between Myhil and Cheney on this subject.) Tests at Quest or Biolab can be done on coQ-10. Status of blood levels of carnitine and NAD are part of the basic Acumen test. The basic test covers ATP profile, SOD, Cell free DNA, NAD blood levels, and Carnitine blood levels.

Anecdotally, various items can be altered with supplements. Blood levels of coQ10, carnitine and NAD can be improved. What this means clinically is another matter.

A third paper of the collaboration, emphasizing treatment, can be found here. It indicates that a majority of patients improve with supplemental treatment. I myself have found that the test can be normalized with aggressive treatment. In the third paper published by Myhill et al, patient betterment was achieved, indicating clearly, as in my case, that mitochondrial normalization (via this test) is helpful.

Dr. Paul Cheney might take a slightly different view of the matter of mitochondrial treatment. He might express that "front-door" treatment of the low measurements of carnitine and co-Q10 is ineffective, and indeed perhaps counterproductive. Dr. Cheney believes that mitochondrial dysfunction in ME/CSF is a self-protective down-regulation and has to be dealt with carefully. This is a fantastic idea and certainly possible. Dr. Robert Naviaux holds similar views with his "playing dead" thesis.

Dr. Cheney himself would perhaps treat mitochondria with high- dose hydroxocobalamin B12, frequent S/Q magnesium injections, transdermal creams or sprays. It is his belief that magnesium in these patients is constantly leaking out of the mitochondria and needs constant replacement. Dr. Cheney might also suggest Isoprinosine (Inosine) and Klonopin. Mitochondria have a klonopin receptor.

Dr. McClaren-Howard and Dr. Derrick Lonsdale, now retired, would suggest thiamine injections or supplementation with an active form of thiamine, as found at Our Kids. Dr. McLaren-Howard would suggest that thiamine is necessary to get magnesium into mitochondria. A transketolase test can be done at King James lab to determine active thiamine levels and the presence or not of a blocking enzyme. This is not an unimportant detail. (Actually King James lab has closed now. Life goes on.)

Dr Joseph Brewer tested PQQ on a number of his patients several years ago, looking to increase mitochondrial function. He also told me about Dr. Richard Boles, who is medical director at Courtagen Life Sciences, a mitochondrial research company. This is another level of mitochondrial research testing and perhaps the wave of the future. Current prices for testing put it far out of reach.

Terry Wahls

And then there is Terry Wahls. I first wrote about Terry Wahls in 2009 on this post. Dr. Wahls recently published a book on her mitochondrial diet, which is a great elaboration of her first book, Minding My Mitochondria. Various ME/CFS patients gain physical strength in taking on her diet, including daily bone broth, seaweed, and fermented foods. Again there is very little that one would call science here and the treatment improvement is only part of the larger picture.

LRT - lipid replacement therapy

The recent ME/CFS conference in SF featured a poster paper of Dr. Garth Nicholson on lipid therapy for mitochondria. Dr. Nicholson has been working in this area for some years. It was interesting to see Dr. Nicholson and Dr. Cheney discussing Dr. Nicholson's poster paper. Here is a recent article on Garth Nicholson's ideas about LRT - or lipid replacement therapy. Dr. Nicholson has made presentations at various conferences promoting his research and treatment into phosphytidyl lipids, especially NT factor. Dr. Nicholson was certainly telling Dr. Cheney how effective NT factor was - and that it really did get into the cell membrane for repair.

Differing with this and giving a second argument would be Patricia and Ed Kane, both of whom have long advocated a separate phosphytidyl lipid treatment, mostly involving IV infusion. This treatment involves their proprietary phosphytidylcholine (PC), sold at bodybio. More recently they have moved into liposomal or microsomal phosphytidylcholine treatment, which proves to be effective. Here is a video of Ed Kane speaking on phosphatidylcholine therapy. It is a winner.

All of the above are different approaches to "feeding the mitochondria" - and improving the function and the number of mitochondria.

Nicotinamide Riboside

Recently I received the heads-up from my friend Nancy Rouch about a mitochondrial lecture by Dr. Robert Rountree, chief medical officer of Thorne products. While this is one long advertisement for various mitochondrial supplements, it does present interesting information. (This lecture will be available for viewing until the end of July.) Dr Rountree suggests the "usual suspects" - or "foods" - for mitochondria - magnesium, co-Q10, acytel-l-carnitine, creatine. He also adds these items: sulforaphan, green tea polyphenals, berberine, quercetin, cucurmin, resveratrol, pterostilbene, melatonin, NAC, and ketogenic amino acids. He spends a significant amount of time on NR - nicotinamide riboside, a precusor to NAD. What he says about NR is quite impressive. NR can be purchased from Thorne as NiaCell and is a proprietary formula developed and marketed by Chromadex. It is not cheap.

Important research is being done on Nicotinamide by collaborating groups in Switzerland and at Weill Cornell. A significant study was published in 2012.

I would be remiss not to mention all the information and discussions on mitochondria function in ME/CFS on Phoenix Rising and Healthrising. Just search for mitochondria and start reading. The internet is an amazing resource - and these sites are just great.

All these suggestions have to be approached carefully and are entirely dictated by trial and error. To me, strictures and dogmas are not particularly welcome. It is well known that each ME/CFS patient responds individually to any particular treatment. So one must work carefully. Taking things slowly, over weeks and months as opposed to days, is often helpful, setting the goal of building a long term framework. This is a one on one game. Incidentally this is not medical advice. I am not a doctor and I certainly do not want to be one, never did.

Here are the first and second page results of this Mito Profile:

The following is commentary by Dr. Myhill of the above page. "The result is made up of three elements. First of all it measures the rate at which ATP is recycled in cells. Because production of ATP is highly dependent on magnesium status, the first part studies this aspect. The second part measures the efficiency with which ATP is made from ADP. If this is abnormal it could be the result of magnesium deficiency and/or low levels of co-Q10 and/or low levels of NAD, and/or low levels of acetyl L-carnitine. The third possibility is that the protein which transports ATP and ADP across the mitochondrial membranes is impaired and that too is measured."

Friday, April 25, 2014

More on Enteroviruses and ME/CFS

A few recent comments on the history of research into enteroviral involvement in ME/CFS are worth highlighting. These comments come from Dr. Charles Shepherd and from Hip, of the Phoenix Rising forums. Hip contributes multiple, important observations to the Phoenix Rising forum and his ideas are always insightful.

From Charles Shepherd:

"I have now met and listened to Dr. Chia on several occasions and I was at the IACFS/ME conference in San Francisco - where he again presented his findings relating to persisting enteroviral infection. I agree with Tony Komaroff that these findings cannot simply be dismissed and we do need another independent group of virologists to see if they can replicate these findings. I have made these points in my own detailed summary of the conference - which is now being prepared for publication. At present, the balance of evidence (much of which was done in the UK by Professor John Gow and colleagues in Glasgow) relating to persisting enteroviral infection in ME/CFS is against any such link. But I think we should adopt a position of 'the jury is still out' on persistent enteroviral infection in ME/CFS until someone has tried to replicate what is a very thorough and interesting piece of virology research."

From Hip:

"Hi Charles Shepherd,

I believe Professor John Gow primarily looked for enteroviruses in the muscles of ME/CFS patients. However, generally speaking, muscle symptoms such as muscle pain are not that common in ME/CFs, whereas gut and of course especially neurological symptoms (e.g. brain fog, sound sensitivity) are the norm. Thus unless you look for enteroviruses in the areas where the symptoms exist, i.e. gut and nervous system or brain, you may not find much evidence for these viruses. Dr. Chia looked in the gut, and found a strong association between ME/CFS and enterovirus infection; but ideally I think you would want to look in the brain and nervous system (in postmortem studies), because neurological symptoms are really the core of ME/CFS. It is known that when enteroviruses like coxsackie virus B enter the brain, they form a persistent infection of the astrocyte cells and the neural progenitor cells. So these perhaps are the areas where we should be looking for enteroviruses in ME/CFS. Two brain autopsies on deceased ME/CFS patients did indeed find enterovirus in the brain.
Viral Isolation from Brain in Myalgic Encephalomyelitis (A Case Report) 2001 J. Richardson www.oocities.org/vitamvas/viralfm.html 
Enterovirus in the Chronic Fatigue Syndrome 1994. McGarry F, Gow J, Behan PQ. www.ncf-net.org/library/enterovirusincfs.htm

Also, it is now known that enteroviruses such as coxsackie virus B form two distinct types of infections in the body: first the normal lytic enterovirus infection, and second the noncytolytic enterovirus infection.  The latter resides purely within human cells, and is not easily detected. Nevertheless, Dr. Chia, and other researchers such as Dr. Nora Chapman, suggest these hard to detect noncytolytic enteroviruses may play a significant role in ME/CFS. Thus ME/CFS studies need to search for both lytic and noncytolytic enteroviruses in ME/CFS patients.

Hi Charles Shepherd,

Also, if you look at the list of enterovirus studies by British researchers from 1983 to 2001 (which includes Prof. Gow's studies), these all found a pretty strong association between ME/CFS and enteroviruses such as coxsackie virus B. This list of enterovirus studies can be found here.

As far as I can see, there seems to be solid and consistent evidence over several decades for the role of enteroviruses in ME/CFS."

Thanks again to Hip and Dr. Charles Shepherd

Tuesday, April 15, 2014

"ad astra per aspera" - Dr. John Chia's ideas taking hold

("ad astra per aspera" - "a rough road leads to the stars")

Several summaries have emerged of the IACFS/ME conference, for those who are interested in the details. The first is the transcription of Dr. Komaroff's summary at the end of the conference. We have Patricia Carter of ME/CFS forums to thank for this. Another summary is by Dr. Charles Lapp. It can be found here

Several paragraphs in each summary caught my interest and both deal with a favorite subject of mine: Dr. John Chia and his research into Enterovirus and ME/CFS.

From Patricia Carter's transcription of Dr. Komaroff:

"Dr Chia reported again at this meeting, as he has in the past, the expansion, the latest summary of data from a remarkable report and a remarkable amount of work, Enterovirus Antigen and nucleic acid found in biopsy samples from stomach in cases and control subjects. Finding very marked differences in the frequency of both antigen and nucleic acid in CFS patients compared with controls. He then also reported that when you took the biopsy specimens that these tests suggested contained enterovirus and injected them into mice that, in fact, you found when you sacrificed the mice, evidence of enteroviral infection, a virus in the mouse, indicating that this thing lit up looking like it might be an infectious agent of the biopsy tissue actually produced an infection in another animal. 

To me, these results are very impressive, but it's also depressing to see that, to my knowledge, no academic enterovirologists have sought to try to reproduce this, not even in bulk, to take the samples that already have been collected at enormous effort by Dr. Chia and test them themselves to see if they get the same results that Dr. Chia does. It's a great shame and I hope it changes." 

In fact two of the infected mice died over a weekend, one on a Friday, one on a Monday. "If they do not believe in death, then what do they believe in?" At least one enterovirologist, and perhaps two,  have worked with Dr. Chia's samples.

And then there is this from Dr. Lapp:

"Dr John Chia is an infectious disease specialist and pathologist from Lomita CA. He and his son contracted CFS/ME and were found to have enterovirus infections in their stomachs (see his article in the Journal of Clinical Pathology, Jan 2009. After treatment with a Chinese herbal called oxymatrine (there is no other known therapy for EV) both have recovered and stayed well. Dr. Chia reported to us on further EV studies from his lab. To demonstrate the infectiousness of EV, Chia injected the lysate (Osterized tissue or homogenate) from 24 EV-positive human stomach biopsies into immune deficient SCID mice. When the mice were later sacrificed, 13 out of 20 were positive for EV in their spleens, but only 1 of 10 control mice were positive. However, Chia could not culture the virus from any of the spleens suggesting that although the infections were transferred, incomplete viruses were formed in the receiving mice. In a second study, Chia obtained pathology specimens from 27 women with CFS/ME who had undergone total hysterectomy or salpingo-oophorectomy for chronic pelvic pain. 24 or 27 specimens stained positive for EV, whereas none of 15 healthy control specimens were positive. Three SCID mice were injected from EV-positive specimens and the mice were sacrificed at either 2 or 5 weeks. Spleens and fallopian tubes stained positive for EV at both 2 and 5 weeks, although spleen stain was less obvious at 5 weeks. Western blot studies of all mouse fallopian tubes demonstrated enteroviral proteins. (Ed. note (Lapp) Dr. Chia is making a strong case for enterovirus as a common trigger for CFS/ME, and these studies imply that the infection is transferable. I found it interesting that chronic pelvic pain was localized to the infected fallopian tube in his patients, and that surgery relieved the pain. Sadly, no one else has taken on the task of confirming Dr. Chia's studies. Also there is no known antiviral therapy for EV - just an ill tolerated herbal preparation. Hopefully someone with Chia's expertise will investigate this further and confirm these important findings!)"

It has been seven long years since Dr. Chia's important paper of potential enteroviral involvement in ME/CFS. No one has significantly picked up on his study. As the backbone of his work, Dr. Chia has studied and revisited the history of ME especially in the UK. He has personally re-ignited important and forgotten associations. Dr.Chia is not coming out of nowhere on this. 

"We need to declare EV as one of the causes of ME/CFS. It has been 30 years!"

"Enteroviruses need to be accepted as one of the causes of this illness this year, or else we will wait another ten or more years before a drug will be available for this disease. You need to ask the researchers at Stanford and at the meeting why they are not working on enteroviruses."

I personally have witnessed several virologists flatten Dr. Chia's work. A prominent virologist (regarding Dr. Chia's work, which I had sent him) gave this blunt assessment: "It's crap". There is evidence that this prominent virologist might have altered his views - and perhaps might be willing to help.

We need to move on beyond these attitudes and find out what Dr. Chia is finding. Dr. Chia himself says: "I have spent considerable time trying to convince that I am right. Now it is time for others to prove that I am wrong."

After this IACFS/ME conference it seems that things are turning in a more positive direction for Dr. Chia's stupendous efforts in trying to get at this nasty illness. For those interested, there is more information on Patrick W. Calvins' Quixotic blog. 

And then there is the recent very exciting news regarding new drugs for Hep C. One drug, Sovaldi, from Gilead was approved by the FDA and is both well tolerated and extremely successful in treating Hep C. Two more amazing Hep C drugs are in the pipeline, one from Abbot and another from Bristol-Myers. There is some hope that one of these drugs might be effective against enteroviruses. "If this proves true, it will make all the difference in the world".

So there is some urgency here, and some real hope - but only if Dr. Chia's work is followed up on. 

Sunday, March 30, 2014

Dr. Joseph Brewer and Mycotoxins, an update

Dr. Joseph Brewer of Kansas City was one of the physicians who did not attend the recent IACFS/ME conference. Dr. Brewer is an infectious disease doctor who has been working with AIDS, Lyme and ME/CFS patients for a very long time. Over the years he has become interested in various treatments for ME/CFS - and has been open to thinking about associated subjects such as Mitochondrial impairment (or down regulation) or Mycotoxin involvement - to describe two of his recent interests.

About two years ago now, Dr. Brewer stumbled upon Mycotoxins and their potential involvement in ME/CFS. Dr. Brewer and his associates, Dr. Thrasher and Dr. Hooper, published their first paper on Mycotoxins and ME/CFS in April 2013. It can be view here. In this study, Dr. Brewer reveals finding 93% (104 of 112) of his patients positive for one of three mycotoxins (there are hundreds of mycotoxins) through a test at Real Time Labs in Carrollton TX. 55 controls yielded no positives.

The Real Time Labs test is a urine sample for Ochratoxin A, Aflatoxin and Trichothecenes (MT). (Real time labs will soon have a blood test for gliotoxin, a mycotoxin associated with Aspergillus.) The initial test costs about $700 and appears to be partially reimbursable. On Dr. Brewer's initial study Ochratoxin A showed up the most, although a good number of patients had more than one and some had "the trifecta" - of all three. Dr. Brewer feels that mycotoxins are not good for patients to have in their bodies -  and that they represent a major factor in their ME/CFS illness.

Dr. Brewer reports that these mycotoxins impair mitochondria function and interfere with cell membranes. Loss of mitochondrial function can cause detoxification problems with other toxins. Poor detoxification might have something to do with clinical response.

Dr. Brewer's previous experience with mold or mycotoxins was non-existent. He is an infectious disease doctor who looks for bugs and tries to kill them. In no way can Dr. Brewer be described as a "mold doctor".

In December 2013, Dr. Brewer, Thrasher and Hooper published a second paper on Mycotoxins and their connection to chronic illness - "Chronic Illness Associated with Mold and Mycotoxins - Is Naso-Sinus Fungal Biofilm the culprit?" In this study they laid out their case based on examination of existing literature, citing case studies.

Faced with this high percentage of his patients with potential mycotoxin involvement, Dr. Brewer was both surprised and perplexed. He began treating some of his patients with heavy duty anti-fungal infusions. In time, again through researching the literature, Dr. Brewer concluded that the most likely reservoir for the mycotoxins was the sinuses. This involved a bit of guesswork. It is Dr. Brewer's thesis that these mycotoxins get into the body and colonize in the sinus. Once colonized and protected by a biofilm, the body cannot get at them and they just stay there forever. It is his belief that they have to be rooted out. He finds in his patients that the exposure can be from the distant past, up to 20 years ago. From Dr. Brewer's point of view, focusing on the sinuses in no way excludes other reservoirs harboring the mycotoxins - the gut, stomach and lung.

Dr. Brewer began treating his patients with nasal Ampho B - and he started getting results. Dr. Brewer works with a nasal drug delivery company called ASL pharmacy. They have a nasal delivery system called Nasa-touch which atomizes the medicinals. In time Dr. Brewer added another nasal drug to bust up biofilms that he believes are harboring the mycotoxins. This is nasal EDTA in combination with surfactant, an ingredient in Johnson's Baby Shampoo.

Two side effects of this treatment are noted. One is that the Ampho B can cause nasal irritation and even mild nosebleeds in a few cases. The second is that the treatment often causes a strong herx reaction as the mycotoxins are exposed and the drug kills them. In both situations, Dr. Brewer moderates or cuts back the treatment and all cases have been manageable.

Dr. Brewer has been surprised, astonished really, by the results of treatment. In his first 100 patients treated, 70% showed improvement, including six whose symptoms completely resolved, including all symptoms of their larger illness.

With treatment, the successful patient's urine Ochratoxin A will go down to zero in a matter of some months. The Trichothecenes (MT) takes longer but it too will diminish with treatment.

Three quarters of the patients treated had preexisitng sympotms of sinus problems. One quarter did not. Both segments showed equal improvement.

Dr Brewer has continued testing and treating more patients. He has now tested 350 patients, 325 of whom are positive for one or more mycotoxins. More Trichothecenes (MT) have been showing up recently in his patient population. He is now treating up to 200 patients and I believe another paper will be coming out soon. Dr. Brewer reports that those patients who have fully resolved and ended treatment tend to relapse and have to go back on treatment.

Dr. Brewer's absence at the recent IACFS/ME meeting has already been noted. How could this happen? How could the emergence of a target for treatment not be acknowledged at this conference? This is all the more unusual in that Dr. Brewer published his first paper a year ago and then gave an exciting presentation at the Lyme conference in October 2013. In this situation, there seems to be a target, a treatment that is relatively benign - and Dr. Brewer is getting results. Doesn't this warrant more attention? Wouldn't it be interesting to find out what is happening here?

Of course, in spite of this, there was quite a lot of discussion of the subject of Mycoyoxins in the hallways of the IACFS/ME conference.

Regarding mycotoxins and ME/CFS we have to ask some questions. The most obvious one concerns the validity of the testing at Real Time labs. At the moment this seems the only lab that does mycotoxin testing. Dr. Ritchie Shoemaker has not been overly excited with this test, or with the idea of nasal colonized mycotoxins. If it isn't mycotoxins that are being knocked out, what is the activity of Dr. Brewer's treatment? A 70% response rate of over 100 patients is impressive. Dr. Brewer himself says that he has never seen such success with a single treatment.

Meanwhile other physicians are beginning to test their patients. A West Coast physicians group has tested over 100 ME/CFS patients for mycotoxins at Real Time labs - and are getting the same high positive results. Preliminary reports on Dr. Cheney's testing of his patients also indicates a high positive response, especially for Trichothecenes. Even Dr. Ian Lipkin indicated that mycotoxins were dangerous, and warranted looking at in ME/CFS. Other physicians, Dr. Chia, and Dr. Enlander, are aware of Dr. Brewer's work and have been encouraged to test their patients.

Tuesday, March 25, 2014

IACFS/ME - and then Mission Delores

At the end of this year's IACFS/ME meeting I headed out on foot to the Mission District and to visit an old favorite: Mission Delores. Over the years, I have come here often, as well as many of the other missions up and down the coast of California. (The mission system was sort of the CDC of the late 18th and early 19th centuries)

Mission Delores and its cemetery are featured in a mistily mysterious scene in Hitchcock's "Vertigo" - one of my favorite films. I am going to watch it again when I get home.

The day was sunny and warm and the sweet smell of dope wafted through the air in the Mission District - as the locals were seeking their medicinal or medical improvements. Crowds of people flocked to a local park to see a concert of the Rollin' Snows or the Scoobie Doos.

The IACFS/ME conference ended Sunday afternoon. The IACFS/ME conference was four, very long days, running March 20-23. Always I find this conference too long - and too broad in its reach. I suppose I understand why the planners do this, as they have a large constituency to please or honor - but they include so many items that I consider to be auxiliary. To me parts of this conference are like watching a bad movie over and over - or falling to one's death off a very tall building.

I come to these conferences as an observer - to watch and listen. I don't think of myself as a participant, but more of an outsider or outlier. I am in the process of my own illness discovery. I figure that I represent my daughter, who cannot be here.

Over time I have learned to be very selective in going to lectures. This time I think that I went to five. I am happier just looking at the poster papers, and talking to old and new friends. This is my fourth IACFS/ME, and it functions as a touchstone of sorts. I just wish it were more focused. I have learned what a focused conference can be. I saw it at the Stanford Conference, I see it at Mt. Sinai, and I see it every year at the Invest in ME conference in London.

Am I giving a mixed message here? Yes I am giving a mixed message.

Dr. John Chia delivered two important talks. It has been seven years since Dr. Chia's pivotal paper was published showing enterovirus protein found in stomach tissue of ME/CFS patients. No one has followed up with this paper. It just sits there with its weight of ME history leaning on it. Meanwhile Dr. Chia continues his superb research - on his own, in virtual isolation. Dr. Chia gave two talks in a section on "Virology Research", chaired by Dr. Jose Montoya. (I hope that Dr. Montoya was listening.) The first talk was entitled "Chronic pelvic pain (CPP) in patients with ME/CFS is associated with chronic enterovirus infection of ovarian tubes" and the second was entitled "Pathogenesis of chronic enterovirus infection in ME/CFS - in vitro and in vivo studies of infected stomach tissue". Regarding the second study, "Of 24 mice injected with VP1+, and RNA+ stomach biopsies, 2 died in two weeks and13/20 (66%) spleen specimens tested positive for VP1 where 1 of 10 controls tested positive for VP1 by immunoperoxidase staining."

("If they do not believe in death, then what do they believe in?"). Of course there is the possibility that these mice died of sneezing fits - or committed suicide.

There was considerable interest during the question period and Dr. Chia answered a host of questions. He also made a hard-nosed presentation, and defense, of his research over the years, stating that "I have spent considerable time trying to convince people that I am right. Now it is time for others to prove that I am wrong". Perhaps soon we will finally be able to answer this question, whether Dr. Chia is right or wrong. I am betting on his being right.

Dr. Maureen Hanson's team gave a talk, "Plasma cytokines in ME/CFS patients and controls before and after a cardiopulmonary exercise test." Dr. Sonya Marshall-Gradisnik's team gave a presentation on NK cells. There has been a string of exciting research coming out of this lab.  Dr. Gradisnik will also be making a presentation in May at the Invest in ME conference.

It seemed a great oversight that Dr. Carmen Scheibenbogen was not giving a talk or a poster paper. I don't think she was even here. I could say the same about other UK or European researchers. Nothing was presented or mentioned about Dr. Joseph Brewer's recent work in mycotoxins. This seemed a slight oversight. Dr. Brewer made a recent presentation at the Lyme conference in October and will follow up at the next ILADS conference. So someone besides myself must know of his existence?

Where were research concerns involving gut ecology, the metabolome, mitochondria, lipid membranes (Yes, it was great to see Dr. Garth Nicholson's poster paper), mycotoxins and a host of important subjects? What world do these people live in? What illness are they studying?

The strength of this conference lies in its poster papers. This year there were several exciting presentations. I took note of Dr. Maureen Hanson's gut biome study in ME/CFS. Dr. Hanson will be giving a talk at the Invest in ME conference this May. She will be able to trade notes with Dr. Simon Carding, who is also working on a gut biome study in ME/CFS. Dr. Hanson reminded me that her colleague, Dr. Ruth Ley, works mostly in the gut biome arena. Incidentally, there seems to be a percolating effort to have ME/CFS patients do their biome study through Ubiome. The objective would be to publish their own biome study. Is this a good idea or what? - and it all sounds vaguely familiar.

There was another study out of Griffith University of the team of Dr. Sonya Marshall Gradisnik. Nancy Klimas and her group had an entire host of poster papers. I hope these poster papers become readily available.

The most interesting poster papers were two by Dr. Paul Cheney. Dr. Cheney has always contributed one or two important poster papers. One yearns for Dr. Cheney to be given a chunk of time to make a full presentation of his ideas. Dr. Cheney does best in three-hour slots of time, so he could have a morning session, a break for him to rest for a half-hour (but does he need it?), and then an afternoon session. This could go on for two or three days. And then maybe we could have a comprehensive conversation of what might be happening in this illness. But, of course, this is not going to happen. Instead we have to content ourselves with Dr. Cheney's self-published studies, and with Dr. Cheney's riveting explanations in front of his poster paper. He gives it willingly and repeatedly.

Asked what he does for his patients, Dr. Cheney says that "he stabilizes them".

I witnessed a few snippy engagements and comments, which are always interesting to me - and which I will keep to myself. I watched old adversaries be cordial and even respectful to each other.

The conference awards dinner had an especially good feeling to it. Nancy Klimas got a top award, which she certainly deserves. Dan Peterson gave the Keynote Address and took us on a stroll down memory lane. He described the history of IACFS/ME meetings, in the process recognizing many individuals in the audience, including Hillary Johnson, the gifted writer. Dr. Peterson showed a short video with 1990's video snippets of the early heroes in this struggle - Komaroff, Cheney, Bell, Klimas and Peterson himself. It was a hoot to see Nancy Klimas as a young clinician/researcher. This video was a lot of fun. Dr. Peterson has a special skill, either natural or developed, of getting the flow going in a positiive direction.

I was surprised, really surprised - and pleasantly surprised - to see Pia and Richard Simpson of Invest in ME receive an award. Never were there two people who have less interest in awards. Instead, they are interested in science - and money to fuel research. So if you have extra money, after giving to John Chia's EV Med Research, write a big check to Pia and Richard Simpson and Invest in ME.

Now that Richard and Pia have been recognized by IACFS/ME for their stupendous efforts, maybe the steering committee of the IACFS/ME group can select a group of "Important People" to actually make the journey to the upcoming Invest in ME conference - and thus learn a bit about how to organize a meaningful conference.

One thing that always, always irritates me about this IACFS/ME conference is the lack of attention to the severely ill. In fact, I have trouble connecting the severity of my daughter's illness with anything that happens at this conference. I do not think that most of the people who attend this conference have the slightest clue as to the true nature of this illness. They look at the half-sick, always at peak times, and draw their conclusions - if they only did a little more exercise.

And it is my belief that they do not want to know. I have observed the displeasure incurred by Dr. Kenny De Meirleir at an Invest in ME conference for presenting videos of very seriously ill patients from Norway, and for the testimony of a young woman who lived in the same house with a severely ill sister and had not seen her sister for four years. And then there is the whole anxiety about showing Voices from the Shadows. It is a very profound and great video, but it is seen as a downer. Well, this illness is a downer.

There is something so frightening about the core of this illness - from which almost everyone turns away. A little of this "ground zero"can be seen in Natalie Boulton's and Josh Bigg's extraordinary film. Dr. Montoya had the wisdom, the courage to show "Voices" at the Stanford Conference. (Dr. Montoya understands, he has learned this.) These totally isolated human beings hold the key - or a key - to the essential nature of this strange and devastating illness. Why are they not studied? Why does everyone turn away? Can we move forward if we are a bunch of cowards? If one is careful, blood, urine, saliva and feces can be removed from these patients (in some cases). If one wants to know what tests to do, I and others can tell you.

The efforts here at the conference and elsewhere to engage or embrace the severe ME patient is pathetic - really pathetic - and this means something.

Maybe this is all an age-related problem? Maybe I am just unable to see all the connecting parts at this conference and put them together? I will have to ask others, back in NY, like Jay Spero, if this is the problem, if this is my problem. In the meantime, I am in a hurry. I am not interested in the one-hundred year fix. I am less interested in stasis and more interested in dynamism, as reflected perhaps in what Dr. Skip Pridgen announced yesterday. Was Dr. Pridgen at this conference?

A number of serious clinicians did not go to this conference - Dr Eric Gordon, Dr. Kenny De Meirleir, Dr. Ritchie Shoemaker, Dr Derek Enlander, and Dr. Joseph Brewer. One has to ask why?

Friday, March 21, 2014

Dr. Jose Montoya and the Stanford ME/CFS Symposium

It is March 19, 2014 and I have come to Palo Alto for a one-day conference at Stanford University. The weather here is ideal - sunny and warm. I take the long, familiar walk up the allee to the conference - past the Caltrain station, past the museum. This is familiar territory to me, having been here many times in the past - for much different purposes. The air is full of anticipation. It is exciting to come to a major university for an ME/CFS conference.

This conference is the product of one remarkable person: Dr. Jose Montoya.

Dr. Montoya has single-handedly forged this ME/CFS research collaboration at Stanford.  There is nothing of its breadth and scope anywhere else in the world.

Seven years ago or more, Dr. Montoya, an infectious disease doctor, stumbled upon ME/CFS. At that time, his burgeoning interest in this illness did not seem to be particularly welcome to his colleagues at Stanford. An outsider might have given Dr. Montoya no chance of making headway in this environment.  Why would an infectious disease doctor want to waste their time on CFS?  In spite of this resistance, Dr. Montoya forged ahead - and he has created a very strong collaborative research team, including the likes of Dr. Ron Davis. It is a remarkable story.

The series of conference lectures was impressive. The morning’s session included Dr. Jarred Younger’s “Daily Fluctuations of Cytokines in ME/CFS patients,” and the afternoon was highlighted by a presentation by Marcie and Mark Zinn entitled “Quantitative EEG studies Suggest Subcortical Pathology in ME/CFS." (Others, here, and  here, will present a more detailed explanation of these lectures and the scientific strengths of this conference.)

The final two lectures were what I had come to see: Jose Montoya and Ian Lipkin.

Dr. Montoya’s lecture “Circulating Cytokines in ME/CFS Patients reveal a novel Inflammatory and Autoimmune Profile” articulated the results of his long-standing research into cytokines in ME/CFS. For a number of years, Dr. Montoya has been looking to create a cytokine signature and he looks like he might have done this. Over the years I have asked Dr. Montoya how his work towards a cytokine signature was progressing. Each time he said that it was going well and that he was taking his time to make sure that “he got it right”. Now the time of “getting it right” has arrived. Dr. Montoya invites criticism of his work in order to strengthen it.

Dr. Ian Lipkin gave his generic lecture, aimed at college freshman science majors. I found it fascinating, but, in reality, he was actually addressing a room full of hard-core scientists.  One wonders. At the end he tacked on additional work coming out of the Chronic Fatigue Initiative at Columbia.  His results continue to be unimpressive - and we wait for publication of some of his work.

A young woman asked Dr. Lipkin about Enteroviruses and ME/CFS. He gave a vague, evasive answer. Later I asked Dr. Lipkin specifically about Dr. John Chia’s work. Dr. Lipkin professed to not know of Dr. Chia, or of his 2007 paper, or actually of any of Dr. Chia’s work. I found this difficult to believe.  Dr. Lipkin did say that he believed that the stool sample work, for which he is hawking support, would reveal Enteroviral involvement. According to others, others that actually know something about Enteroviruses, this is not possible.

The sold-out conference took place in a large room filled with round tables with chairs and three large screens for slides. It was an ideal situation in which to see and hear the presenters, and the format was constructed in such a way as to encourage interaction. It was a great conference, tightly focused, no bullshit.

Obviously, Dr. Montoya’s efforts have paid off and he now has a momentum to study and treat ME/CFS at Stanford. How lucky can we be? He and his collaborators are producing significant results and garnering attention from the larger science world. This is what is necessary in this ME/CFS illness discovery - serious consolidation and collaboration. The great success of this conference only guarantees that Dr. Montoya and his colleagues will be back with more information, more research, more results, and more hope in the very near future.  Dr. Montoya has done what everyone wants to do in life - but very few can actually pull off. I take my hat off to this fellow.

If one wants to learn more about Dr. Montoya, check out this video:

Sunday, January 19, 2014

Dr. Carmen Scheibenbogen, Berlin Charite

A most remarkable study on ME/CFS was published January 15, 2014.

The study, by Dr. Carmen Scheibenbogen and her team at Berlin Charite, can be found here

From the study:

“By comparing memory B- and T-cell responses of CFS patients with healthy EBV-infected subjects, we observed a profound deficiency in EBV-specific B- and T-cell memory response in the majority of CFS patients resembling the deficiency of EBV memory responses described in autoimmune diseases [56] and chronic HIV infection [57], [58], [59].”

The following comments are by anciendaze, who writes commentary on various forums, including Phoenix Rising, a forum that provides terrific information. Anciendaze writes with great knowledge, insight and clarity.

“This looks like the real thing. The highly specific immune impairment certainly looks like a virus defending itself. A complete lack of patient IFN-gamma response to the EBNA-1 challenge is striking. Latent replication allows the virus to benefit from clonal expansion of infected cells in response to immune challenges from unrelated pathogens. This is one feature I felt pretty sure about earlier, and only retroviruses seemed to have the required ability.”

“The parallels with HIV and HCV will make it much harder to ignore. Contrasts with SLE should illuminate the murky subject of autoimmune disease. We still don't know what initiates the process, since most ME/CFS patients were exposed to EBV long before the appearance of symptoms.”

I got the heads up on this research when I heard Dr. Scheibenbogen give a talk at the Invest in ME conference in London in May 2013

Three quarters through her half-hour talk I was struck by what she was saying. Dr. Scheibenbogen and her group looked at the normal EBV antibodies (IgG, IgM, EBNA) of their patients. In doing so they were surprised to find that 10% of these patients had low EBNA. The team took this to be another secondary indication of immune abnormality in a subset of CFS patients and they decided to look further at all the patients. They did not attach a particular meaning to this lower EBNA beyond that it was one more hint of immune abnormality in CFS patients (specifically in regard to EBV). She expressed her belief that this abnormality just represents the tip of an iceberg. Based on this finding, they developed a much more sensitive assay to access B cell antibody response, by looking for the response against more than 2000 peptide fragments of the whole EBV virus itself. From the almost 100 proteins of the EBV virus itself, they took the most relevant and cut the proteins in pieces and tested them. This sophisticated testing - looking for an abnormal response to EBV - found in the first round of assays that 2/3 of CFS patients had a different response than controls. They have continued to work with larger number including patients from Norway as well as using other diseases as controls. This altered EBV specific response is their basis for developing a diagnostic test for a subset of CFS patients. Her lab is collaborating with a company in Berlin in developing a diagnostic test for a subset of ME/CFS. (Patients in Germany are referred to as CFS).

In this talk Dr. Scheibenbogen indicated that her ideas about ME/CFS parallel those of Dr. Amolak Bansal, an immunologist in London, who also gave a lecture in 2013 at Invest in ME. She also gave a significant nod to the work of Dr. Oystein Fluge and Dr. Olav Mella.

Dr. Scheibenbogen and two of her colleagues attended a one-day pre-conference meeting of researchers on May 29, 2013. Thirty some researchers met to discuss a particular topic or focus for research. Last year the subject was Infections, Immunity and ME. The year before the research conference was on Autoimmunity. Of course getting researchers together to talk is a splendid idea. A good number of them come from outside the field of ME/CFS.

Invest in ME produces a modestly priced DVD of their annual conference. I suggest that those interested readers buy this DVD and view these lectures. The entire thrust of this conference and pre-conference private research discussions are quite extraordinary - and are driving towards a consolidation of research into this illness.

This conference is guided by Richard and Pia Simpson. Their nine or ten year struggle to focus research is really paying off with increasingly wide ranging connections with the sole intent of getting at this illness. I cannot say enough positive things about Invest in ME and urge American clinicians and researchers to attend this conference. I have witnessed myself the exchanges that happen at the pre-conference dinner, and on the conference day itself. This conference is the place to be if you want to encounter cutting edge research about this illness.

Regarding the publication of this paper yesterday one wonders what Dr. Ron Glaser will think of it? Are we going to have a confluence of ideas here - or the more typical disconnect that we associate with ME/CFS research? Certainly the researchers in Australia – Dr. Sonya Marshall-Gradisnik and Dr. Don Staines – will have their eye on this continuing research, as will Dr. Fluge and Mella. All of these researchers have made presentations at Invest in ME for the last few years and have participated in the pre-conference day discussions.

Further comments by anciendaze, to whom I am greatly indebted.

“This paper looks like the real thing. The immune impairment they describe is highly specific to EBV. One of the surprises in the main text is that none of the CFS patients they tested with a challenge involving a polypeptide from EBNA-1 produced an IFN-gamma response. This fits perfectly with the hypothesis of latent replication. Their results concerning deficits of polyfunctional immune cells with three different functions helps explain earlier mixed results concerning EBV. Researchers were looking for much less specific immune impairment.”

“Please note that the full text of the referenced paper describes tests for EBV infection which go a great deal beyond common clinical lab results. They also report that tests showed a great deal of latent replication must be taking place. Common assumptions in testing for EBV are based on active infections and antibody response to them. Few labs test for DNA of latent virus in immune cells. This paper specifically reports that certain evidence of RNA, produced by active infections, was absent or reduced. It also shows a crippled response via IFN-gamma. Under these circumstances it is unreasonable to say that it can't apply to you because you don't have unusual EBV results from standard clinical labs.”

“PCR testing, both qPCR and RTPCR, is part of the suite of tests used, but only part. They also used multiparameter flow cytometry to count immune cells with multiple markers. Even studies doing clinical flow cytometry have typically been limited to sorting cells by a single marker. (Note the disclaimer at the bottom of the page about the research instrument.) This would prevent them from detecting the specific deficits of polyfunctional immune cells found here. Beyond that they used ELISA and stimulated cell culture immunoassays. It's all there in the text.”

“This is the kind of battery of modern research techniques which has so often been absent in studies of ME/CFS. I'd say they really examined their early data and were guided by it in choosing that immune challenge with EBNA-1. This is not an example of confirmation bias behind a single favorite hypothesis.

 A further comment from anciendaze:

"Normally, we think of a DNA virus like Epstein-Barr Virus (EBV) as being either active or latent, and assume it isn't doing much of anything while latent. EBV actually has several latent states. Latent phase 0 describes the least active state, which pretty well matches what we assume. There are also latent phases I, II, III. During these states it is possible for viral replication to take place. Active phase replication is typically lytic, with host cells being destroyed to release virions. Replication during latent phases need not destroy the host cell.

This has a major implication in the context of clonal expansion of immune cells. In this case stimulated immune cells divide by the normal process of mitosis, producing 2, 4, 8... daughter cells. This can lead to millions of cells producing a powerful response to an antigen detected by a small number of cells.

EBV infected cells have one or more episomes inserted inside the nuclear membrane. These are just plasmids, loops of DNA, floating around loose, not inserted in chromosomes. If clonal expansion just distributed a few episomes among many daughter cells, most of these cells would not be infected. However, if the virus is able to replicate viral DNA without destroying the host cell, it then has the ability to infect all cells resulting from clonal expansion. This has the potential to produce large numbers of infected cells without most of the indications of viral infection.

In order to exploit clonal expansion EBV doesn't even need to produce virions. It only needs to trigger replication of DNA strands, something host cell machinery does naturally during mitosis.

We know that retroviruses do exploit clonal expansion through passive replication of inserted provirus. (This has been a major problem in the fight against HIV.) We did not know this was often going on in a very common human virus which does not insert genes in chromosomes. What we did know was that most ME/CFS patients continue to show polyclonal expansion (of B cells in particular) while the disease state persists, but we could not find a single pathogen responsible. Immune response seems to be confused and often misdirected. Some patients do show autoantibodies (ANA, ATA, ACA); many do not, at least by current standards used for autoimmune diseases. Considering the limited understanding of those diseases, it may be time for a reevaluation.

In the past we have frequently heard that evidence of EBV infection was inconsistent or absent in ME/CFS patients. This research shows that conventional lab results give a very misleading picture, and offers some reason why. Furthermore, the evidence available now paints a picture of cells with viral DNA and nuclear antigens, but reduced or absent RNA from lytic replication, cytokines and antibodies. It really appears that this virus is crippling specific immune response to itself.

This has implications for a wide range of clinical tests, and for a number of diseases besides ME/CFS."