Guest Blog: K Update

I am in no way suggesting by posting this that what has worked for K works for everyone. However, the treatments we have used are very low risk and non-invasive. In my opinion, supervised trials of these safe, gentle therapies should be widely available to ME/CFS patients. Val’s account of K’s remarkable progress contains many clues about how to improve. The credit is all K’s. She did the work. I am so proud of her for taking control of her health and finding her own path to wellerness. She is a most remarkable young woman. Now, for some good news from Val. (Here is the link to her original guest blog in March 2012: Seeing Jamie.)


K skiing

K skiing


It’s been just over a year since I first posted here about my daughter’s (K) experiences with Dr. Jamie’s treatment, so I wanted to do an update to share the really fabulous news about K’s progress.  In preparation, I’ve been re-reading old posts and correspondence, and it’s sure been a lesson in how effective our minds can be at suppressing bad memories — at least the memories that don’t generate PTSD — although some of those 3 a.m. trips to the ER had the potential.

K has continued to improve beyond our wildest dreams over this past year.  These are the symptoms that have improved:


Her pain has decreased so much that she’s basically off any prescription pain meds. She’ll take a very small piece (e.g., 1/8th) of a 5 mg Percocet tablet for pain in the evenings, but often goes without it now.  This is compared to what she was taking when she first saw Dr. Jamie, when she was using a 25 mcg fentanyl pain patch supplemented with 15 mg oxycodone tablets 4 times/day.  K will still have pain that puts her on the couch with her heating pad some evenings.  But it’s nothing compared to how excruciating and unremitting it previously was.  She also went off Lyrica a few months ago, and this time the withdrawal was barely noticeable.


A big shock is that her sleep/wake cycle has straightened out!  She still takes tizanidine at night for sleep, but she can go without it and often substitutes Benadryl instead, believe it or not.  She actually has a REGULAR bedtime now, after all of these years.  She is still a bit of a night owl – bedtime is midnight or 1 a.m. and she usually sleeps until 10 a.m. – but she’s not just endlessly cycling around the clock, and is reliably awake during the daytime.  What a difference being reliably awake during the daytime has made in her quality of life!  As I described in my post a year ago, she’s had terrible sleep since she was born, so I never thought we’d see this.


One of K’s scariest symptoms was fainting without warning.  That stopped happening over a year ago.  When Dr. Jamie did the 5-minute standing mini-tilt test with K last October, K’s vital signs did what they were supposed to do and the test didn’t bother at all.  The first time Dr. Jamie did this test, we had to stand right next to K to make sure we could catch her if fell, and it was very painful for her. Now she can stand up long enough to take a really looonggg shower (annoys the heck out of my husband) without all the blood pooling in her feet and ankles and no dizziness.  She can even stand up in the kitchen long enough to help with dinner!


She is able to be on the internet again finally!  Her cognitive limitations that made it impossible for her to do much more than watch tv and read romance novels a few hours a day are gone.  Having an iPad also helps.  Now she’s once again voraciously reading the news and the kinds of complex political and economic analyses she used to love, posting on facebook and in forums, handling twitter, and even doing some writing.


This, too, has straightened out.  No more terrible cramping and it all works normally for the first time in her life.  Interestingly, she’s just discovered that she does much better by avoiding gluten.  She was tested for celiac when she was having extreme gut problems in her early 20’s, but was negative.  And she’d tried a low-carb diet in the past, which seemed to make no difference at all previously.  But now, also at Dr. Jamie’s recommendation, she’s finding that avoiding gluten and just about all processed foods is helping a lot.


The most amazing thing of all is that she’s now capable of vigorous physical exercise with no PENE!!!  The background on this is that we’ve relocated to Hawaii – just in time for Dr. Jamie to move her practice to Arizona…  But we fell in love with it here and moved this past year.  Hubby and I got to Hawaii on September 1st.  K wasn’t able to get here until early October because of complications from bringing her dog into Hawaii, but then had a full month of treatment with Dr. Jamie and basically finished detoxing off the prescription pain meds.  She spent December and January in Seattle and handled it really well, despite it being cold, dark and damp, which formerly made Christmases there a really bad time for her – not to mention how difficult it was for her to handle the flights.

But here is the big news:  She was well enough by late January to go SKIING!!!  It’s something she has always loved, but she had to stop when she was about 16.  We hadn’t even kept her equipment.  So, she used one afternoon’s worth of energy to go get the rentals she needed.  Then the next day, she was able to ski two runs in the afternoon, with no PENE.  AND, she did it again the next day!!!  (Apologies for all of the exclamation marks, but I really can’t help it.)

When she got back to Hawaii at the beginning of February, she started swimming.  Vigorously.  For increasing lengths of time and over increasing distances.  In the ocean, with waves and sharks (seriously) and currents.  Doing the crawl – you know, that swim stroke that has you lifting your arms over your head and uses the muscles in your neck, shoulders and back, where her worst pain has always been located???  And she says it feels wonderful – no PENE from this either!  In fact, she craves the exercise now and goes at least every other day and often daily.

Oh, and Fatigue

I’ve never known what this is supposed to be about.  She felt like shit all the time.  She was in so much pain and misery she could never sleep well and any kind of exertion made everything worse.  Or, she could never sleep well and so was in constant incredible pain and misery, and any kind of exertion made it all much worse, as well as making her feel fatigued.  She desperately tried to sleep as much as she possibly could to escape the conscious experience of how unremittingly miserable she was, but it didn’t alleviate the misery, no matter how much she kind-of slept, and being constantly “fatigued” was a by-product of the entire mess.  She was completely incapacitated and felt horrible all the time, awake, asleep or in between.  She could barely move on most days.  Is that “chronic fatigue?”  “Feeling dead tired all the time” is the least of the categories of misery this disease imposes.

But, anyway, she still gets pooped out and has to lie down a good part of every day.  She still has nightmares that interrupt her sleep from pain and misery some nights. She isn’t close to having the energy we see that her friends are able to expend in a day.  She doesn’t faint, can get out of bed, dress herself, exercise, drive, stand, shower, shop a little, cook a little, talk on the phone or in-person for longer periods, chat online or text more and for longer periods, read and comprehend intellectually challenging stuff, and doesn’t pay for it.  When she overdoes, the payback is limited to the next day and she’s not flayed by it for the next week or weeks or for months.  She can travel on airplanes without being destroyed for weeks afterwards.  She’s not in bed 24/7 with her eyeshade on and earplugs in, and doesn’t have to crawl to the bathroom.  Is she less “chronically fatigued?” Yes, she feels less “fatigued,” but focusing on fatigue as the major symptom of this disease is ludicrous.


Taken together, this all adds up to much more of a real life than she’s had in 10 years.  She’s not even close to being able to work or sustain a social life yet.   But it seems like in a few more months…?

Next Challenges

The next big step is resuming her education.  Not only has it always been near and dear to her heart, but it’s also looking like she may be able to do paid work eventually and even possibly in a profession.  It’s been 7 years since she finished the last online college course that she was able to complete.  She tried for three more semesters, each of which ended abysmally.  As any young person who has this disease has experienced, dealing with our educational systems’ rigidity and lack of comprehension has left lasting scars, not only to her self-esteem but also in response to the plain old distrust, insults and abuse that are visited on our very ill young people by so much ignorance.  Speaking of PTSD, we’ve labeled all of that as Post-Traumatic-Student-Disorder.  We’re not only dealing with the residue of bad educational experiences, but there is the additional discomfort now associated with being an older student. As we move through the processes required to get her enrolled in online classes again, I’m realizing that she’s not the only one with this version of PTSD!


In looking back at my blog post from 14 months ago, I see that I said, “I’m pretty sure that if we only stopped here with oxygen, hyperbaric and Deplin, all these gains would fade over the next 2 years.”  Well, we’re only just a couple months past a year out from that self-protective prediction – we didn’t want to let ourselves have too much hope.  After all, there are stories around of PwME who go into remission for years at a time, attributing it to some combination of treatments or other, only to have it fade away over time or end with another crash.  So, it’s possible this past 20 months of improvements may be another example of the relapsing/remitting nature of this disease. There may not actually be a link between the improvements and the high-flow oxygen, Deplin, the mild HBOT Dr. Jamie provided over a month in March 2012, and then again between October and December this year, dietary tweaks and getting her off all of the prescription meds.

But K has inadvertently done her own within-subject research on whether it’s these treatments that are actually responsible for the improvements.  For example, there have been occasions over the past year when we were unable to arrange for her O2 in the midst of our moving and travels.  She reports that within 2-3 days of being off the O2, her energy starts decreasing, then her pain level starts increasing, then the brain fog starts returning.  She hasn’t had to go without it longer than 2 weeks, but she REALLY noticed the difference.  The effects of going without Deplin are milder.  Its absence also increases her fatigue and brain fog, but doesn’t have as much of an effect on her pain as the absence of O2 does.  For a former treatment-resister of the youthful “if it’s not a magic bullet that makes me feel better immediately, I’m not going to do it” type, she’s become very dedicated to making sure, herself, that she has her O2 and Deplin now.

And now there is this happy little study from Turkey that came out the other day:  “The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome”.  In a very preliminary way, it supports what K and some of Dr. Jamie’s other patients are experiencing.  That is, if you pulse the patients with high dose oxygen, their symptoms abate.  And, based only on K’s really positive, immediate happy experiences with HBOT vs. the slower, but continuing improvements from daily high-flow O2, I’m betting there’s a dose-response relationship that wouldn’t be hard to demonstrate at all, if there were researchers who had the funding to look into it.  Of course, there is absolutely no money to be made by Big Pharma on this, so we can be sure that the NIH, CDC, the CAA, etc. won’t ever fund research on such a simple, inexpensive, accessible thing as high-flow oxygen from a tank or concentrator, which insurance and Medicaid/care in the US cover and can be delivered to the bedsides of even the sickest patients.  But, I sure do hope these lovely guys in Turkey continue looking into it.

Once again, I apologize for the excessively long post, but I have two more things to report/say.

A Step Back

K went back on Lexapro last fall.  In the Oct-Dec timeframe when K was upset about moving to Hawaii and was going through the rapid withdrawal, her mood tanked.  Going back on it helped, even at the much lower dose she is now taking.  I think she’s ready to go off it again, but I’m just an observer these days.  With all of these improvements, she’s really able to be in charge of managing her own treatment. Yay!!!  Dr. Jamie wasn’t in favor of K going back on Lexapro last fall, but K was sure she needed it then, and Jamie was so good about supporting K’s decision. They’ll figure it out.  As a Mom who spent years in pure panic mode, it so is nice to have K able to evaluate these things for herself.  It’s even nicer that K has a Dr. who puts her ego aside, understands how complicated and interesting it is for K to be emerging from the horrible prison of this illness, and knows how to support K as she begins catching up in life.

Rate of Improvement, New Benefits from Old Ideas, and New Sensitivities

The strangest thing about all of this is that K’s rate of improvement has massively accelerated since she got past the opiate and other prescription med withdrawals in January (except Lexapro, as above).  Whereas the first year or so on Dr. Jamie’s treatments gave her slow, but steady improvements, over this past 3-4 months, the pace has accelerated.  Was all that garbage interfering with and slowing down the rate of her improvements?  Probably.

Or, what if there are thresholds in this disease where old hat treatments/changes actually can make a difference, if we could somehow stop the cascade of failures?  I don’t discount the beneficial effects of K getting off the dozen or more prescription meds her previous physicians had thrown at her (and I permitted in desperation – Mom guilt).  But, beyond that, over the past 20 months, it’s as if every system that failed sequentially as her disease progressed has been coming back online.

As she was getting sicker and sicker, it was like this disease attacked one system at a time.  As I wrote in my post last year, she had sleep and gut problems from birth, and those have been the most recent improvements.  The OI/POTS and migraines came next at puberty.  Then, the excruciating pain and fatigue/PENE soon after, but distinctly later by a year.  Then the complete hormonal failures.  Then a wild and crazy exacerbation of her gut problems that had her in the hospital numerous times for a year.  And finally, the complete cognitive shutdown.  Over the past 20 months, it’s as if the systems that control those symptoms at first stuttered into occasional action, then have eventually kicked in to functioning somewhat close to normally again.  I’m reminded of Paul St. Amand’s claims about how “reversal” works on his guaifenesin protocol.  It has been interesting how the symptom sets have improved in the reverse order from how they initially shut down.

It is also so strange how things that made no difference at all or made her WORSE while she was getting sicker and sicker are now making a positive difference.  I mean, really, how weird is it that she’s now dedicated to vigorous exercise to control her pain and it actually makes her feel better overall with no PENE?  How can that be?  And how strange is it that she’s suddenly discovered she is gluten intolerant?  Another small change is that arnica actually works for her now to give a little pain relief now and then, when it was one of the first treatments we tried and did nothing at all to help her back then. What’s with that?

Wishes, not Conclusions

I wish we knew why Dr. Jamie’s treatments have been so good for K.  I wish we knew what has been making these treatments work so well for her, but not some others.  I especially wish we knew whether K’s upward trajectory will continue and the improvements will last.

I’ll continue to post updates as this evolves.  A little more wellerness as every month goes by has been unbelievably wonderful.

Hate this disease, but I sure do love Dr. Jamie.  Thanks so much, dearest friend.


K after swimming

K after swimming


The Doomsday Scenario

An important new paper has been published: Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels. Muegai et al. The et al includes Pathak who published the paper with Coffin which identified XMRV as a virus created in the lab. From the title you might think it is about cancer and blood vessels; however, look at the last sentence of the conclusion:

… the results suggest that xenograft approaches commonly used in the study of human cancer promote the evolution of novel retroviruses with pathogenic properties.

Here is the crux of the matter:

The evidence that XMRV was generated as a consequence of studies aimed at elucidating the pathology of human disease is disturbing in that it highlights long feared dangers of use of xenograft tissues in clinical settings, including porcine valves [14,15]. Of even greater concern, the results support the idea that attempts to develop better therapeutic interventions might inadvertently promote the development of pathogenic viruses. However, the following observations refute this possibility: First, although xenotropic and polytropic MLVs have been described as far back as 1970 [16,17], as of yet there has been no validated evidence of human infection by this class of viruses. Second, despite intensive investigation of XMRV by many laboratories [1,18,19] there is no evidence that XMRV is capable of inducing transformation of cells [1,20], although there is recent evidence showing that XMRV infection of LNCaP cells resulted in modest increases in proliferation, and invasion of cells into Matrigel in vitro (Pandhare-Dash et al. [4,21]).

Are you reassured? Their first point is a basic logical fallacy. Absence of proof is not proof of absence. Nobody ever found it, so it isn’t there. Their second point says XMRV, the manmade gamma retrovirus about which we know the most, isn’t dangerous, maybe. What a relief. Yet even they are now admitting, XMRV is not the only one out there. They found a new one for this paper. So now there are at least two, and no longer such a remote possibility.

The studies described herein address these questions, and show that at least one other XMRV-like virus exists, and that the virus evolved the ability to infect human cells and to express gene products that impact tumor pathogenesis.

But no need to panic. The folks that brought you this mess, will figure it out one of these decades. Recombinant Origin of the Retrovirus XMRV, now a year old, where they argued that the chances were “vanishingly small” that XMRV wasn’t created in a lab in the mid 90’s, while studiously ignoring the fact that other similar events were in fact quite likely. So they are finally admitting that the chances aren’t so small, since there have been so many chances. Now there are two. Or is it three? This paper, identified a cell line in use at the NCI that produces another infectious XMLV: The Human Lung Adenocarcinoma Cell Line EKVX Produces an Infectious Xenotropic Murine Leukemia Virus.

Inductive logic is forbidden. No connecting the dots allowed. And who can blame them, when it has been recently demonstrated that dot connecting gets you burned at the stake in the scientific community. Have to start with what we know and carefully build step by step, hoping that the pyramid ends with something coherent. God forbid, we should decide that we have learned something new, something so big that a top down approach should be employed. It is so big in fact, it could explain why 133 million of our people and 55% of our children have chronic illnesses in the US, and why 20% of adults in the developed world have an autoimmune disease. ME/CFS is little. It is time for a revolution. It is an emergency. I wrote that same sentence in 2010 and nothing has changed.

How many young people have been felled by ME/CFS since then? I know about one teenager that was treated in 2010 with antiretroviral drugs and recovered. His mother posted on this blog anonymously at one point, but was presumably prevented from going public. Sick for 8 months, better in 6 weeks. Treated for 6 months and remained in remission off treatment, as far as I know. How did that case report not  make it into the literature? It is unconscionable. I am sick of hearing about how an N of 1 is irrelevant. An N of 1 is called a case report. If important enough, it leads to a pilot study and then a clinical trial.

This burden of chronic disease in children is our replacement for the 20% that used to die before the age of 5 of infectious diseases. So instead of dead children we have live disabled ones. What is going to happen to all these disabled children? Whether the cause turns out to be an activated HERV, or an exogenous simple animal retrovirus (alpha, beta or gamma), the use of antiretroviral drugs is a logical thing to try. It is unfortunate that the only drugs available to us were developed for a retrovirus that is phylogenetically dissimilar from the simple viruses in question here, but even so, AZT, Viread, and Isentress have had a positive effect on a number of patients with ME/CFS, incomplete and, after a while, not clearly worth it, but there is a noticeable positive response in a percentage of patients, which appears annecdotally to be greater than placebo. That should be a beacon in the fog, not a reason to make the drugs taboo. Dr. Snyderman’s cancer is stable on full HAART. Shame on both the scientific and medical communities for ignoring him.

What would happen if you gave antiretrovirals to children at the time of an autistic regression? I know your government wants you to believe that the astonishing increase in ASD, now acknowledged by CDC at about 2%, is because we got better at diagnosing it. While that is undoubtedly partially true, since it is now a common disease, it is insulting to our intelligence to reassure people on that basis. It is only 2%, so no worries; your individual chances of having an autisitic child are still low. But what are your chances if you have CFS or a first degree relative with CFS, or autism, GWI, Lyme Disease, PANDAS, RRMS? These diseases are running rampant. Certain families bear an incredible burden of illness, including early aggressive reproductive and hematologic cancers. It is frightening, even if you look at only one disease at a time, but as part of a preapocalyptic whole involving the health of the species? Terrifying. Virus, injury, genetics. Many perfect storms.

Whatever happened to vaccines being inappropriate for people with immunological abnormailities? Given that patients with various immunological problems now encompass a very significant proportion of the population, the entire vaccine program needs to be seriously reevaluated. Continuing to give ever increasing immunological challenges to a patient population with seriously declining immunological health, for diseases that are extremely unlikely to cause long term morbidity or mortality, is no longer clinically justifiable in my opinion. It is medically incorrect and unethical at this point to take the current vaccination schedules for civilians and the military at face value, especially in light of the implications from this paper, and the recent acknowledgement that GWI is not in fact limited to the veterans of Desert Storm, but still occurring.

The upcoming FDA meeting will no doubt give mention to many more dangerous treatment options than AIDS drugs. AIDS patients got the best. Lots of very clean drugs to work with that cost billions to develop. There are probably many drugs on the shelf that didn’t work well enough for HIV, but might have activity against the viruses we are dealing with. My guess is antiretrovirals will not even be on the table for discussion.

IT IS STILL HAPPENING. Every single day. New people getting sick that should be treatable. The scientific community should not be allowed to take their own sweet time about this. It is not acceptable in the midst of this pandemic for them to withhold anything clinically relevant, whilst expressly trying to prohibit the off-label use of legal, safe drugs that might help patients who are in dire straights, patients suffering beyond belief, for whom there is no meaningful treatment. But the culture is to “burn at the stake” any scientist that steps out of bounds, as we have already witnessed. Doctors too, for that matter.

Look at the tunnel vision in this paper. It is all about cancer and xenografts. No mention that gamma retroviruses cause neuroimmune diseases in vivo, as well as cancer. No mention that there are aspects of modern biotechnology that could be causing the same or worse problems than the ones described in this paper, notably hybridoma technology. And nothing about vaccines, the sacred cow, which contain foreign DNA and are parenterally introduced, given in ever increasing numbers and combinations to an ever more vulnerable population. Live attenuated vaccines are grown in cultures known to express animal retroviruses, e.g. chick embryo, mouse brain culture, monkey kidney cells. Here is a list of vaccine excipients and culture mediums used for production from Wikipedia. And that’s now. Can you imagine what the technology was like in the 50’s, 60’s and 70’s? Viruses successively passaged through mouse brains, passaged meaning brain sucked up with a big needle and injected into the next mouse, then eventually the resultant sludge was injected into or fed to people. Now we can tell what we are doing and we are still doing it. Chemical Induction of Endogenous Retrovirus Particles from the Vero Cell Line of African Green Monkeys.

The paper under discussion mentions the “plasticity” of these viruses. They recombine and rescue each other. But scientists aren’t allowed to connect the dots, even when obvious, as it should have been a couple of decades ago, since it was known by the 70’s that these viruses were there. Here, written by a couple of the scientists who have recently contributed to the distortion of the true significance of XMRV, telling us in 1995 what they feared, but did nothing about. I have posted it before and try not to repeat myself, but in light of this paper, it deserves to reappear.


The assumption that these viruses could not harm humans was made on very shakey ground; everybody was having too much fun tinkering to be stopped by a few qualms. There were a few absence of proof experiments. What hubris! Now, this is the only explanation for ALL of the observed phenomena, encompassing the environmental and genetic aspects, the variations on a theme so clear to see in the various patient cohorts. The Lipkin paper came up with positive serology in 6% of the study population, patients and controls, to a very nasty defective murine retrovirus that produces Env. That particular mystery should be a high priority by now. Why is the 6% not being studied intensively? They found positive serology in human beings to pathogenic retroviral Env in Lombardi et al, they found it in Lo et al and they found it in the Lipkin study. The 6% may be, probably is, only one of many. But no need to panic.

On the personal side, as I reported last time, I went back on Viread. I again noticed an uptick in function and ability to withstand stress 6 or 7 weeks after starting it. My blood pressure is now well controlled on additional antihypertensive medicines, in fact better controlled than at any other time in my illness. I started Isentress a couple of days ago and plan to add Kaletra very soon. Ali remains remarkably stable on Viread and Isentress for 3 years now. Her life is very full. She is productive and happy. Her most limiting symptom remains MCS.

I just returned home after a trip to Tucson seeing patients. The first 5 patients I saw were 3 women almost exactly my age and 2 men, both 48 years old and sick for almost four decades. That strikes me as a bit much for coincidence. I have noticed for years, and especially since I’ve been writing this blog, that my December 1953 birth date seems to be at the peak of a bell curve for middle aged ME/CFS women, suggesting something went out horizontally. Was it when we were born? We received the oral polio vaccine, on a sugar cube, but we wouldn’t have all been the same age when we got it, since it wasn’t released until 1961. And we know that there were outbreaks before the polio vaccine. Papers have documented certain years with peak waves of onset. All of this fits with the idea that it has happened multiple times and each time, it looks a little different, e.g. average age of onset, gender susceptibility, most prominent symptoms, thus the misconception that it is a heterogeneous problem.

Just as there were many retroviral invasions in the distant past, in this paper we have emerging evidence that it has happened again, on a grand scale, over a very short period of time. There are most likely already some viruses that are endogenized in families, since it has gone unchecked for so long. The very high incidence of PCOS in young ME/CFS women may be consistent with a retrovirus invading the germline. When I first wrote about this possibility, I thought it was irreparable, a true doomsday scenario, but it is not. Evolution will deal with it, even while our fertility is dropping at an alarming rate. Deletions will occur, possibly in not very many generations. We will learn how to stay methylated to keep our viruses quiescent. We will eventually learn to manipulate epigentic factors in our favor. But like carbon emissions, we need to stop it now. A retrovirus or pieces of a retrovirus now and again, repeated exposures to endocrine disruptors, synthetic hormones and steroids, add a little Bt toxin, a “cover your ass” CT scan and a couple of radioactive tracers for worthless imaging, courtesy of your doctor, and voila! A recipe for the disaster that is occurring, while nobody panics.

Today’s song: You Haven’t Done Nothing by Stevie Wonder

MS Light?

What’s occurred in the last 30 years is criminal, Mikovits says today. “Mothers and fathers got sick, their children got sick.” But with heightened attention, she adds, patients are likely to get help soon. Even lacking a causal pathogen, biomarkers in this patient population can be studied for clues. “We can find therapies for the CFS patient population even before we determine the exact cause,” Mikovits says.
Chasing the Shadow Virus by Hillary Johnson Discover March 2013.


As I said last time, I started Viread again, because I became dangerously hypertensive, a few weeks after stopping it. I had a significant drop in my BP, almost to normal from days 6-12, then it went up again, not quite as high as before, but very high. After much fiddling, it is now controlled, but I had to add additional antihypertensive medication. Happily, after a month back on Viread, there is a downward trend again and I’m hoping I’ll be able to wean from the extra treatment soon. This is not the first time I’ve had this problem, but it was the worst episode yet, and was related in time to stopping Viread. I have been feeling significantly better for the last week, and am also back to baseline productivity. I flared for the first few weeks I went on Viread the first time also. I am going to Tucson to see patients in a couple of weeks and when I come home, am planning to restart Isentress and then Kaletra. I really didn’t want to go back on Viread, but it does seem that I’m getting a payoff again from it. I went off because I wasn’t doing well, and things got even worse, now better back on. I am just reporting, not explaining why or how. The disease is a relapsing remitting illness all on it’s own and changes may or may not have anything to do with the last thing you did.

My reading lately has been about retrotransposons and HERVs, especially MSRV, multiple sclerosis-associated retrovirus. Here is a cutting edge, must read paper, senior author Hervé Perron, whose name appears on most of the important papers on this topic: The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity.

MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease.

The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation.

Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing-remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS -<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.

The above paper concludes that exogenous virus production is unlikely. Particles have been identified in MS patients going back to 1989: Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles. 

In fact, a virus was identified in MS in 1975. Look at how far they got with the technology at hand at that time: Multiple sclerosis-associated agent: transmission to animals and some properties of the agent.

In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease.

Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis contains electron micrographs of MSRV particles.

Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a ‘chain-reaction’ triggered by infectious agents in multiple sclerosis?

The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation.

Endogenous retroviruses represent about 8% of the human genome and belong to the superfamily of transposable and retrotransposable genetic elements. Altogether, these mobile genetic elements and their numerous inactivated “junk” sequences represent nearly one half of the human DNA. Nonetheless, a significant part of this “non-conventional” genome has retained potential activity. Epigenetic control is notably involved in silencing most of these genetic elements but certain environmental factors such as viruses are known to dysregulate their expression in susceptible cells. More particularly, embryonal cells with limited gene methylation are most susceptible to uncontrolled activation of these mobile genetic elements by, e.g., viral infections. In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases. Epigenetic factors controlling HERV-W ENV protein expression then reveal critical. This review addresses the gene-environment epigenetic interface of such HERV-W elements and its potential involvement in disease.

Here is a paper about something that could turn into useful therapy, overlooking the significant risks associated with the administration of monoclonal antibodies and the inherent risks involved in hybridoma technology, which involves fusing human cancer with animal B cells. GNbAC1, a humanized monoclonal antibody against the envelope protein of Multiple Sclerosis-associated endogenous retrovirus: a first-in-humans randomized clinical study.

Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis-Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.

In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. identifier: NCT01699555.

However, rather than injecting antibodies to gobble up the viral envelope, given the real and theoretical problems with monoclonal antibodies, it would be better to keep Env from being produced in the first place. Maybe a protease inhibitor is the missing link. AIDS drugs didn’t work well until they had PI’s. Dr. Snyderman’s data suggests this was the case for him. I am happy to report that he remains stable at 32 months. Does a response to a PI imply exogenous virus? How far does a HERV have to get in its reproductive cycle before a PI would do some good? SFFV is a defective virus with a pathogenic envelope. If MSRV produces variable particles, some of which appear complete on EM, is it ever infectious?

Reading about MS, thinking about my own clinical presentation and putting it together with everything we have learned since XMRV entered our lives, ME/CFS may exist on a spectrum with MS, in the same way that Aspergers Syndrome is part of the autistic spectrum. Certainly, we are a variation on a theme. I have called it MS light before and I think it is a good working hypothesis for now. Up To Date’s summary on MS is here. Note the many similarities, genetics, epidemiology (including cluster outbreaks), possible problems with the Hepatitis B vaccine. It seems to me our best hope post XMRV is to ride on the coattails of MS, even though it is pathetic that we need to, given that there are at least three times as many of us.

I’m getting lots of questions about what I think of the paper published by De Meirlier et al. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. I am not going to evoke all the reasons why I might have a problem with this paper, whatever it says. I have moved on. Much of it is documented elsewhere on this blog.

Taking the paper at face value, problems with it are the tiny sample size, from patients that I hope had very serious GI complaints, compared to the patient population as a whole, since, presumably, they warranted a duodenal biopsy. I would like to take this opportunity to emphasize that I am completely opposed to taking any risk of harming fragile patients with unnecessary procedures in order to study the disease. There is no reason to do duodenal biopsies on garden variety ME patients, so the patients in this study should have had significant inflammatory bowel disease, not just IBS. The procedure carries a significant risk. A duodenal punch biopsy can result in death. There is lots of tissue to study without resorting to that. Fresh tissue is harvested all the time for other reasons, there is lots of material to autopsy and lots of specimens in paraffin, which is what was used in this study. My small intestine in paraffin is stored down the street at the local hospital. And plasmacytoid dendritic cells can be harvested from peripheral blood.

The simplest explanation for the findings in this paper is that there was a range of proteins consistent with a generalized activation of HERVs. Many things can transactivate HERVs including recombination events and exposure to exogenous retroviruses. Perhaps they didn’t name the HERV because they were all transactivated? This is what you might expect in someone with inflammatory bowel disease. We have no idea whether these people had a neuroimmune disease or not. The fact that they had a range of symptoms that would qualify for a clasification of CFS is neither here nor there. Endogenous retrovirus-K promoter: a landing strip for inflammatory transcription factors?

There are quite a few papers worth reading in the references, but they missed one:  Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells.

I hope they are right. It would set us on a path to catch us up to MS, where we belong. However, the paper is so vague. Antibodies to proteins expressed by a generic HERV. This negative paper was also just published: Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients. It is good news for us that this avenue of research is being pursued.

I expect the De Meirleir paper to get shot down or be ignored completely. The scientific world will probably only read it for laughs, considering the source. They didn’t find a “real” virus this time, so nobody needs to spend millions of dollars to prove it wrong. MSRV was ignored for decades, even though it is associated with a more sympathetic disease than ME/CFS. Progress with it has been glacial, revealing the non-urgent, almost lackadaisacal attitude of the biomedical world towards activated HERVs, even one that was shown to produce viral particles over 20 years ago. In any case, infectious or not, there is increasing agreement that HERV W is associated with MS and can transcribe an Env protein which is neuropathogenic.

And another related illness: HERVs expression in Autism Spectrum Disorders.

I am particularly happy to report that my friend Dr. Mikovits is doing well through it all. She has received many letters of support and asked me to let the community know that she is fine and excited about the future. She is consulting with respect to drugs and diagnostics. She continues to lecture. Currently, she is working on projects with Dr’s Ruscetti and Lipkin, and, in a translational capacity with several medical doctors, Eric Gordon, Chitra Bhakta, Derek Enlander, Paul Cheney, Michael Snyderman and myself.

This excerpt is from an email to me a couple of days ago when I asked her a few questions for this blog:

Planning for the April 25th FDA meeting…a two day meeting to get drug companies and clinical trials avoid the failure of Hemispherx..we have a huge opportunity about that..tell the patient community I will go there and work to bring them the drugs that are out there as soon as possible..we as a community do not have to go back to basic research where we are decades away..we can translate what we know.. write about that …move forward..

My background is in antiviral drug mechanisms and epigenetic drug development..I am going back to my roots to focus on drug development in infectious/ inflammatory disease…I can now apply my expertise and extensive network to ME/CFS..

Dr. Lipkin said this about her in Nature, only a few months ago:

I feel very badly for Mikovits, [her co-author] Ruscetti and Harvey Alter [a hematologist at the NIH Clinical Center in Bethesda, Maryland, who led one of the CFS studies]. Mikovits in particular — she has lost everything. She can be wrong but she’s not a criminal. She has been honest in a respectful, forceful way and said that we have to conclude that we were wrong. You can imagine how difficult it must be, and I think she should be applauded. Lots of people wouldn’t have the balls to do that. She has come across as a scientist who really believes in the importance of truth.

Dr. Judy has come a long way since then, pulling herself up by her own bootstraps. I am in awe of her resilience. Handed lemons, she is making excellent lemonade. Stay tuned.

Today’s song: Titanium by David Guetta

Twists And Turns

The world will not be destroyed by those who do evil, but by those who watch them without doing anything. ~ Albert Einstein

When I started this blog, I promised to share my journey as it unfolded, before knowing the outcome. My goal was always to explore and learn, not convince anybody I’m right, since I clearly don’t know. So here’s what’s happened since I last wrote. A day after I wrote the last blog, I ran out of Cozaar (losartan), forgot I hadn’t put it in my pill case for the whole week and missed two doses. Before restarting it, I checked my blood pressure and it was 212/127. I’ve missed losartan other times in the last few years, but never with such a severe elevation and always responsive to restarting the med. But this time, my pressure stayed ridiculously high, even after adding a second drug, amlodipine, which I have used as a second drug before, but haven’t needed in several years. I have a long history of labile hypertension and a period of persistent severe hypertension was the problem that ended my Emergency Medicine career in 1996.

It happened about a year after my first symptom, following a period of unrelenting stress. The blood pressure elevation came with a feeling of doom. The numbers were often high, for most of a year, despite all the drugs my doctors threw at it. Initially my academically inclined physicians were excited by creepy medically unexplained symptoms in a colleague. They thought I had something cool, like a pheochromocytoma or carcinoid. They sent off all their esoteric tests and when it was all negative, or almost negative, they concluded that I either had a world class case of white coat hypertension or was crazy and not taking my meds. Indeed, the independent medical exam ordered by my disability carrier concluded I could return to the ER if I took my antidepressants like a good girl, despite my protestations that I wasn’t depressed and my blood pressure was very high at home too, with nary a white coat in sight, besides my own.

It is a long, sad story, filled with injustice and stupidity, mine and my doctors’. I’ve written some of it here before, but I’m mentioning it again now, because this current episode was so similar to what happened then. The hypertension occurred in the context of an abnormal stress response and autonomic dysfunction/instability. Because my dysautonomia occurs in the setting of hypertension, I don’t have POTS per se, but a variant. The autonomic nervous system wasn’t even part of the discussion back then, and here is why. The first paper in the medical literature on POTS, or orthostatic postural tachycardia syndrome, was published in 1993, only 2 years before my first symptoms and had no penetration as yet to an average work-a-day doc: Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?

Even by 2002 when my husband developed severe dysautonomia, it was not part of the common medical lexicon, as it is beginning to be now, finally. Recognizing autonomic nervous system dysfunction as a core deficit in Gulf War Syndrome sufferers is a big step from our old concept of PTSD. So what do we think? Was it a new phenomenon? Or were all the doctors who came before me such poor physical diagnosticians that they missed it without the benefit of tilt tables?

As I have previously reported, I did not have viral onset CFS, but a very atypical onset and course, which was clinically more similar to Gulf War Illness than ME or CFIDS, as it was called then. If I’d been in the military at the time, instead of a civilian working in a trauma center, I might have landed in that bin. Now, 20 years later, it is finally starting to occur to the scientific and medical communities that the problem is in fact more extensive than the 250,000 soldiers who got sick at that one particular place and time: Report: New veterans showing Gulf War illness symptoms. Could this be a prelude to asking questions about the pathophysiological similarities observed in the various neuroimmune disease cohorts, diseases which were rare or unknown just a few decades ago? What risk factors are shared by vets with GWI-like illness, autistic children and patients with ME? Why is that question not being asked in the context of the public health emergency that it is?

So I’ve had problems with my BP all along, but nothing as severe or sustained since way back then, until now. I’m intolerant of most classes of antihypertensives, but have evolved an approach to BP spikes that works for me, basically temporizing until the episode resolves on its own, since experience has taught me that aggressive treatment will make me bottom out suddenly at some point. I’m better off accepting a mild elevation than pushing my luck, with such an unstable baseline. Hypotension is probably worse. Certainly, it feels worse. I did all the things this time that usually help, and everything else I could think of. I mentioned in the last blog that I had reduced my dose of Deplin as I was feeling sensitive to it while things were getting worse in December. I went back to my old dose of 7.5mg to see if that was the problem. Mood improved, but blood pressure didn’t. Went up to max dose on the newly added calcium channel blocker and took supplements and herbs which support vasodiliatation and relaxation. High dose Epsom salt baths. Biofeedback. Everything worked briefly, but still with regular readings above 200 systolic, plus the continuing waves of dread I was experiencing, so similar to the beginning of my illness. I was trying to figure out which 3rd drug to add soon if something didn’t give, knowing that all the choices were likely to be problematic.

Faced with only unpleasant choices, and since the problem was related, at least temporally, to discontinuing Viread, I decided to restart it. I was in no way excited or positive about it, but felt it was the least of the bad choices. Since stopping it, I had been feeling better in some important ways, with notably less nausea and possibly feeling a little stronger. So despite a strong preference for going ‘au naturelle’, and tired of being a guinea for drugs developed for patients with a different disease by drug companies with no interest in ours, and very tired of copays, I nevertheless found myself surprised to be back in a place where restarting antiretrovirals was looking like my best option. When Ali and I first started arv’s in early 2010, I believed we had a virus which had been confirmed at 3 labs, including the Cleveland Clinic and the NCI, plus published supportive in vitro testing. It made sense then, but now? I spend my energy working on natural solutions for patients. My own goal was to get off any drugs I possibly could. But the blood pressure wouldn’t give, trumping all my reasoning. I went back on…

On the 5th day back on Viread, with a resurgence of nausea worse than before I stopped, I was cursing drugs and drug companies, when my symptoms broke, like a fever. The high blood pressure let go, as did the other symptoms that came with it in a chicken or egg fashion, such as the fight or flight feeling from too much sympathetic tone. It isn’t just a number on a blood pressure monitor, but part of an entire symptom complex. Since things turned around 6 days ago, I’m doing better than before I stopped it in the first place. I have no logical explanation for that. BP is adequately controlled, at least pretty good for me. I am planning to restart Isentress in a week and I am considering lopinavir as a 3rd drug. See the last blog for Dr. Snyderman’s data demonstrating his response to lopinavir. Kaletra is currently part of a regimen undergoing a clinical trial for a beta retrovirus, similar to MMTV, in PBC (primary biliary cirrhosis), with evidence for growing, slowly, as is always the case when it comes to investigations of human retroviruses other than HIV.

Why might this recent experience of mine be interesting to other ME/CFS patients? Hypertension is not usually a finding in this patient group. However, vascular instability is. Increased sympathetic tone is. An abnormal stress response most definitely is. All of that apparently got worse and now better again, in an A – B – A fashion, taking, stopping and restarting Viread. And, distinct from my usual predicament, I could actually measure something. Numbers! BP now coming into line after 11 days back on, starting to decrease the second antihypertensive, didn’t have to start a 3rd class with intolerable side effects. I really wanted off, but I am not afraid of these drugs, so here I am again, and so far, so good.

After watching me twist in the wind for the last couple of months, Ali is planning to sit tight with respect to her antiretrovirals, enjoying her good fortune and relative stability. For those readers who are interested in her regimen for PCOS, she has decided to discontinue Actos for the long haul, even though it helps her in the here and now. She has started a slow wean, planning to increase metformin if necessary.

Having learned the hard lessons personally with respect to unvalidated tests from small labs with special interests, I came across this on Medscape and think it needs to be shared: Lyme Culture Test Causes Uproar. The link works if you have an account, but here is the first paragraph and exerpts of the article about a culture for Borrelia burgdorferi from a lab called Advanced Laboratory Services:

A new chapter in the Lyme disease controversy opened in September 2011 when Advanced Laboratory Services, Inc, announced the commercial availability of a new culture test for Borrelia burgdorferi. Some Lyme patient advocacy groups and physicians began encouraging patients to have the $595 test, but others are concerned about the early commercialization of the still-unvalidated test. This concern may result in changes to how the US Food and Drug Administration (FDA) regulates so-called “homebrew” or laboratory-developed tests (LDTs)…

Soon after Advanced Laboratory Services’ initial public announcements about the new culture test, emails and public statements attributed to Dr. Burrascano began appearing on Lyme-related Internet sites, including comments that the culture test was approximately 94% sensitive and 100% specific.

Dr. Burrascano told Medscape Medical News that the validity of the culture test was established using blood samples provided by physicians and that the identity of Borrelia was confirmed by its ability to grow in Borrelia-specific media, by its characteristic appearance on darkfield microscopy, by reacting to published Borrelia-specific polyclonal and monoclonal immunostains, by DNA polymerase chain reaction (PCR) at 2 different loci, and by direct DNA sequencing. These data are so far unpublished…

And here is the disclosure statement at the end of the article:

Dr. Burrascano has disclosed no financial interest in the laboratory, in the Borrelia culture, or in any intellectual property and receives no commissions from the tests. Dr. Burrascano is senior vice president of medical affairs and medical director for Advanced Research Corporation, a contract research organization with the same president and corporate address as Advanced Laboratory Services, Inc. Dr. Mead And Dr. Green have disclosed no relevant financial relationships.

Oy vey. Here we go again. Another unvalidated test to justify bad treatment. What’s wrong with the unvalidated tests they’ve been using all along? The ones that are almost never negative for various tick borne diseases? And this, hitting the presses coincident with the WPI promoting Dr. De Meirleir’s lecture, yet another doctor with a history of profiting from unvalidated lab tests. I think I’ll stop now, so my blood pressure stays down, and end on a positive note.

I just had the pleasure of reading Hillary Johnson’s very fine piece in the latest edition of Discover Magazine, available to non-subscribers soon in print at a newsstand near you. Her most excellent account of the XMRV saga, “Chasing The Shadow Virus” sheds journalistic light on the events that occurred and raises desperately needed awareness for our shadow illness. I was close to the events, have my own perspective and strong opinions about what happened and why; this article rings true to me, maybe because I have this same quote on my phone in a text message, “I still see the footprints of a retrovirus..” Yes, Pandora, the box is open forever. Denial is dark and powerful, but eventually, the truth will shine through.

We can discuss possible esoteric mechanisms from now until the cows come home as to why Viread stops an inflammatory process which causes my blood vessels to go into spasm: Brain Microglial Cytokines in Neurogenic Hypertension. But why not start with the most likely explanation? It is a drug which inhibits retroviral reverse transcription. Certainly it is a real possibility that it is doing what it was designed to do.


Big Yellow Taxi – Joni Mitchell

Our experience with antiretrovirals

Two months shy of three years, I discontinued antiretrovirals, began after receiving reports of positive XMRV cultures from VIP Dx in January 2010. Ali and I started AZT and Isentress in March 2010, added Viread in May 2010, discontinued AZT in Feb 2011. I discontinued Isentress in August 2011 and remained on Viread monotherapy until two weeks ago. Ali continues on Viread and Isentress. We also tried the protease inhibitor Lexiva, and I tried it a second time, but didn’t tolerate it.

We both improved for the first year, but it wasn’t a clean experiment, as I’ve said all along. We did other things concurrently. When we started, I thought we’d ride on the coattails of HIV and have viral load measures in a year or two. We sent lots of blood to the WPI and Dr. Mikovits was studying us, but the specific results were never shared with me and are now lost, with the rest of Dr. Mikovits’ data.

We stopped AZT after 11 months, with no way to monitor, to prevent long term toxicity. Neither of us noticed much of anything coming off of it. By the summer of 2011, I knew there would be no help with monitoring and came off Isentress in anticipation of our both stopping the drugs. I wanted to see what happened to me first, before Ali came off. I tried to stop Viread shortly after. Nothing noticeable happened when I stopped Isentress, but I felt worse after a few days of stopping Viread, better when I went back on. I did that two other times by the first part of 2012, with the same results.

Meanwhile, Ali continued to go uphill. Me not so much. In hindsight, I wish I had not stopped Isentress, since Ali continued to improve and I didn’t. I functioned fairly well, with lots of travel and stress, through my last trip to Hawaii in October, but then crashed pretty hard. By Christmas I was feeling very poorly. I always say, when things go south, stop the drugs, so I did. Since then, I am feeling a little better. I am having less nausea than I was having on Viread, but my nausea predated arv’s by several years and when I went on arv’s, I didn’t think it was worse. I am now on only Cozaar, baby aspirin and hormones. As I got sicker, I my tolerance for Deplin lessened, interestingly, and I am now taking an OTC dose of Folapro 800mcg once per day. I have increased nutriceutical and nutritional support, am doing biofeedback, and am about at my October baseline, I’d say.

Here’s an interesting paper about raltegravir, though reactivated Herpesviruses are not a part of our clinical picture: A Drug Against AIDS Could Be Effective Against The Herpesvirus and here’s the paper: Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain. It isn’t new, but I hadn’t seen it before. Here’s a new one: Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase:

We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1.

So there are still scientists working on this really creepy virus that was created in a lab and infects human cells, but fortunately, not particularly well, though the statement below is not very comforting. Severe Restriction of Xenotropic Murine Leukemia Virus-Related Virus Replication and Spread in Cultured Human Peripheral Blood Mononuclear Cells:

In summary, our results show that XMRV replication and spread is severely restricted in PBMCs, but these cells can serve as a reservoir for generation of infectious virus that can potentially spread to cells that express low levels of these restriction factors.

It’s good for us that they are still studying it, because, although we don’t have XMRV, we still may have something very much like it. I still find the extreme resistance to trying HIV drugs for something besides HIV to be completely bizarre. AIDS drugs have been noted to be useful on occasion for Sjogren’s, MS and HTLV, but then generally nobody follows up even so. Here is the latest reference on clinical trials for HTLV associated leukemia: Clinical Trials and Treatment of ATL. I aways find it disheartening to read about HTLV, because it has been neglected for so long, even though it was isolated by Bernard Poiesz, Francis Ruscetti and their co-workers in Gallo’s lab over 30 years ago.

Speaking of dishearteningly slow progress, look at this paper from 2005: Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. From the abstract: “Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level.” And this one from 2010: The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation. “In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases.” But nobody wants to try antiretrovirals on these patients?

Why is it such a stretch that the concepts learned from the AIDS epidemic could have vast utility beyond the treatment of that one well funded infection. Where are the drug companies??? We don’t have specific drugs and we don’t have any way to monitor the effects of the drugs we do have. So we are effectively stopped from studying something promising. A good percentage of the people who tried antiretrovirals experienced mild to moderate improvement for a period of time. Very little harm happened, even though it was a completely random and uncontrolled experiment. The drugs are not scary compared to many drugs that are given to ME/CFS patients every day. I can tell you there is a lot more possibility of harm from the SSRI’s, pain and sleep meds which are routinely offered, with no chance of positively impacting the disease process.

So, we as a community paid VIP Dx a bunch of money to tell lots of us we had XMRV. They are lucky the damages were only financial and not large enough individually for anybody to spend the effort to recover. Several people have sent me this: Transcribed  and posted on MECFS forums from Mass CFIDS/ME & FM Association’s Fall 2012 Lecture: (YouTube video of lecture by Dr. Byron Hyde)

Byron Hyde: The other thing he [Lombardi] says is that he studied under Dr. Suhadolnik at Temple University. So I picked up the phone and I [Hyde] phoned Robert [Suhadolnik] – who is a wonderful wonderful researcher man – and I said: ‘Tell me about Lombardi – who studied Chronic fatigue Syndrome under you and did research with you’.

He [Suhadolnik] said: ‘He never did’.

I said: ‘Oh ? What do you mean he never did ?’

[Suhaldolnik:] ‘Well, he came here for a few days and I got rid of him because he was a nuisance and he didn’t knew what he was doing and that was it.’

…one minute later:

Byron Hyde: I figure they (WPI) made somewhere between two and three million dollars on that [XMRV-test]. People all over Europe, people all over Canada, the United States, were sending their blood in. The other thing which is interesting is the Whittemore-Peterson advertises as a charitable institute. It is not a charitable institute. It’s got a Cameo institute on the floor below which is for fee for service. And they are there to make money.

Here is the WPI version: Date: January 6, 2013 (link)

Vincent C. Lombardi, Ph.D., Director of Research (…) He later continued to work in CFS-related research in the laboratory of Dr. Robert Suhadolnik at Temple University, studying the interferon regulated RNase L antiviral pathway and its involvement in CFS. (…)

The bio then goes on to give Lombardi credit for Dr. Mikovits’ ideas. Of course they also give him credit for the collaboration with Silverman. You’d think he wouldn’t be so quick to take credit for that. So let’s see what is left. He got a PhD at University of Nevada, Reno in 2005 and then invested in Redlabs and went to work running tests on humans. What was his dissertation about? When did the training happen that qualified him to be culturing retroviruses from humans? What prior experience did he have running a clinical lab? It would appear that anything he learned after finishing school must have been from Dr. Mikovits. Actually he was already trying to take credit for her ideas when I was there. He took me to breakfast in December 2010 and told me that it was really his discovery. He was rewriting history already, a dishonest post-doc, trying to discredit his mentor to a new colleague.

Please read Larry’s comments after the last blog (link). We were robbed and the WPI is still sucking up all the money. I expected a federal investigation of the lab, holding them accountable for the money they made on the tests, but it hasn’t happened. There seems to be no critical thinking on the part of the government agencies in question. So they have the grants, which will run their multi-year courses, irrespective of whether the money is producing anything meaningful or not. Nevermind that it is a very significant chunk of all the government money available to study our disease and it might be much better used. Why not give that money to Dr. Ruscetti or Dr. Lipkin? Or give it back to Dr. Mikovits, so she can get on with her work, as should have happened in the first place.

Posted last night on Facebook by Joan McParland:


As most patients are aware, Dr. Judy Mikovits has been forced into bankruptcy due to recent unfortunate events. A number of members discussed this issue at our monthly meeting last night and have made a decision to send some financial help to Dr. Mikovits.

The main reason for this action by some members of the support group is to show our support and also in an attempt to return the unreported kind acts and dedication shown to us by Dr. Mikovits on her numerous visits to N. Ireland.

Many more patients, worldwide, who have contacted me recently have also witnessed and benefited from the caring nature of the human being behind the scientist.

As from today, Dr. Mikovits is now free to return to work, we wish her well and hopefully she will be able to continue her dedication to helping find the answers we all so desperately need and deserve.

The entire situation has already been well summed up by Ian Lipkin’s quote below..

“I feel very badly for Mikovits, [her co-author] Ruscetti and Harvey Alter [a hematologist at the NIH Clinical Center in Bethesda, Maryland, who led one of the CFS studies]. Mikovits in particular — she has lost everything. She can be wrong but she’s not a criminal. She has been honest in a respectful, forceful way and said that we have to conclude that we were wrong. You can imagine how difficult it must be, and I think she should be applauded. Lots of people wouldn’t have the balls to do that. She has come across as a scientist who really believes in the importance of truth.”

On a much happier note, Michael Snyderman is still stable on full HAART. Stable cancer for 31 months. No chemo brain. And still no interest from the scientific or medical communities??? It is a travesty.

Dr. Snyderman’s update…

My study so far shows:

1. The combination of AZT+raltegravir has activity but is not sufficient to maintain the response.

2. Tenofovir has activity but is not sufficient to maintain the response.

3. Lopinavir has activity which so far is longer than previous responses. More data is necessary to know how long this drug will work.

4. A trial with more cancer patients is indicated.  We need to know what are the predictors for response and what is the optimal drug combination.  What is learned from cancer patients would potentially be valuable to patients with CFS.

Click to enlarge

Click to enlarge


Tonight’s song: Slip Sliding Away by Simon and Garfunkel

“2013 will be a year of optimism, opportunity and HOPE”

Dr. Judy’s bankruptcy was final yesterday. She has lost everything financially. Let’s hope the vengeance is now complete. Her homes are being sold and she still doesn’t have her notebooks. She isn’t working as a lab scientist because of the Whittemore’s defamation of her character, despite Dr. Lipkin’s support.

And still the WPI asks for money from the community? For what? They have not published one paper in the year and a half since Dr. Mikovits was fired. Instead they have spent a bunch of money to ensure she is completely stopped. What kind of people would do that? Why wouldn’t they want her to be able to work? To live her life? She gave them five years, trying to help their daughter, but wanted to follow the truth instead of the money, so they did everything they could to destroy her. What’s in those notebooks that they are so concerned about? There is no intellectual property, since XMRV is not a human retrovirus, but a lab contaminant, so there must be something incriminating, something that leaves them vulnerable. But they won. They have the notebooks.

From a big picture perspective, as affects the patient community, the whole misadventure was so wrong, it’s hard to count the ways. We were robbed, on many levels. From a personal perspective, it is still incomprehensible to me that the promise we felt, back when Dr. Judy was being promoted like a rock star, has turned to dust. However, she has told me repeatedly that they have taken her money, but they can never take the most important things from her. From an email last night, after reading my draft for this blog, copied here with permission:

The copies of my notebooks prove my total innocence. I did my job and beyond…their actions prevented the truth and prevented me from getting work, and not only me, my students as well…but as you say it robbed the scientific and patient communities of data paid for by federal dollars and donations to a “non-profit” institution. I could NOT LIE or ALLOW the truth to remain hidden or support those who would not tell the truth in order to take advantage of a vulnerable patient population.

Their intellectual property was unraveling when it was found that XMRV was a Silverman lab contaminant..what they are and were afraid of is that they will be held liable for the fraudulent testing.. Lombardi and the Whittemores lied for 3 years and they all had a financial interest in VIPDx. There simply cannot be intellectual property or diagnostic testing for a virus that does not exist in any natural organism!!!

From my personal perspective it is incomprehensible, that in the United States of America, all of my constitutional rights can be denied in order to cover up the truth  …They do not want me to work because they are that vindictive. They know I live for my work in cancer and neuroimmune disease and for patients everywhere. They know my work is my life ..they thought they could take my integrity..but you know what ..THEY FAILED!  Because Lipkin applauded my integrity and succeeded at showing the world what Silverman and Lombardi did to this patient population..THEY are the COWARDS and I have my honor and my integrity but most importantly of all, I have the support and confidence of the patient population, not just the CFS patients but the cancer, Chronic Lyme, Autism, MS ALS, Parkinson’s.. that is, ALL the patients to whom I have dedicated my life.

You see, my life was never about money and never will be. I am still working as a volunteer, I enjoyed coffee with two CFS patients yesterday and a cancer patient this morning, before I went with her to an appointment. I have never stopped being a patient advocate and will continue to be one in 2013. As one of my courageous friends with aggressive Parkinson’ s wrote in a Xmas card: “2012 was a year of change and loss,  faith..we all needed tremendous faith to survive 2012!! 2013 will be a year of optimism, opportunity and HOPE”.

Today’s song: I Will Not Be Broken by Bonnie Raitt

Back To Basics

I have always found this to be a trying time of year, even before I got sick. Our family is one of blended traditions and we often wind up celebrating both Chanukah and Christmas, making the whole ordeal go on and on (bah humbug:-). My husband and I thought we had fulfilled our obligations on that front, but now we have little kids at home again. Our eldest daughter Julie, who is half native American, moved back home last year with her two children who are Pomo Indians, and our son is home from his first semester at Tulane. Talk about a mish mosh!

I am having one of those days where even my arms feel heavy. Hey, who turned up the gravity? I feel tremulous, but it doesn’t show. I would like to go to a Christmas party tonight, but I’m not sure at the moment if I’m up for it or not. I’m replaying my whole tape loop about not wanting to disappoint. It doesn’t mean I won’t feel good to go when the time comes, but it’s up in the air at this moment. I’ll use my oxygen, take an epsom salt bath, and probably get the boost I need. More bothersome than the weakness though, with which I’m accustomed to struggling, is the emotional reactivity that comes with more inflammation. I’m sure many of you can relate…

That particular symptom was one of my first. It started just a few months after the birth of my second baby at 40, and it made me feel like I was becoming a different person. For those of you that don’t know me, I had gradual onset of symptoms, no PEM and no diagnosis for a decade, followed by incorrect diagnoses. I haven’t been bothered by this particular symptom for quite a long time and reexperiencing it is sending me back to the exploration of biofeedback that began when I first became ill in 1995 and was looking for a non-pharmaceutical solution for this and other alarming symptoms. In addition to neurofeedback with Cygnet, which I use in practice, I’m enjoying trying out some of the innovations for biofeedback hometrainers and stim devices on the market now. Advancements in electronics have made for easier to use, more effective and less expensive devices. I am particularly interested in them, because most of my patients can’t access a neurfeedback therapist and I had some devices way back when that might be helpful in this context. I’ll report on this subject at some point in the near future.

The FDA committee’s rejection of Ampligen filled me with mixed emotions. As it has been clear for a long time that only a minority of patients do well on it, and as it has some significant downsides, I’m happy for the would be non-responders who will be spared yet another therapeutic failure. On the other hand, other patient groups with real diseases are allowed to try toxic treatments that have only a small chance of success. I am of course concerned about the people who need the drug being able to get it, but the tragedy for all of us is Hemispherx’s failure to figure out who to treat with their drug; thus they have contributed nothing to our understanding of the pathogensis of our disease. They have also sent a loud and clear message to other would be drug developers to avoid CFS like the plague: SHAREHOLDER ALERT: Pomerantz Law Firm Has Filed a Class Action Against Hemispherx Biopharma, Inc., and Certain Officers

The same problem with patient selection is now happening again with the early experimentation with Rituxan: patient selection is random and there are no markers to follow. If you are sick enough, want it and can pay for it, you can be a guinea pig. I predict the stats won’t be good, for the same reason that the Ampligen results weren’t. There may well be a subset of patients that would have a higher hit rate, but nobody knows which ones. For me, it’s even simpler than that. I don’t want anything to do with it, personally or professionally, if it can kill. ME/CFS is a relapsing remitting illness. MS light. The best place to start is with the safest things, try to encourage remission, which requires synergy of global strategies.

One day soon, coming to a Quest or LabCorp near you, we will have a whole genome sequencing test that insurance will pay for. Then we will finally learn something that might change our options. But until then?

Still trying to understand why oxygen works so well clinically, in the setting of patients with increased oxidative stress, I’ve been reading about “mitohormesis”. Please take a look at these papers. This is a very important concept. Oxygen has been used to good advantage in the autism community and I still believe that the diseases are related, the differences in disease expression being due to the developmental stage at onset of illness. These papers describe the mechanism by which repeated doses of increased reactive oxygen species produce cellular resistance to stress. So repeated doses of hyperoxia in patients unable to exercise might produce better mitochondrial function over time, a theoretical framework for a clinically observed phenomenon.

Since I returned to practice, I’ve been intending to turn my attention to supplement recommendations for my patients. To date, I haven’t had a protocol and my advice has been random and half-baked. The passing of Rich Van Konynenberg left a great hole in our community. I feel a great personal sense of loss, because he and I intended to share with each other and it didn’t happen, completely due to my limitations, all my small supply of energy going to my practice. Now that I am studying the subject in depth and coming across his lectures and posts on the internet, I am very upset with myself. He was a brilliant, giving man. Generous of spirit. I am learning a great deal from him now, since he shared his ideas so freely.

As my second year back in the world comes to a close, my most powerful interventions remain high dose pulsed normobaric oxygen, Deplin, B-12, organic SCD diet, hormone balancing, stopping meds if possible, eliminating environmental toxins and biofeedback. I don’t think such a program will cure anyone, but I believe it can help a lot and is almost risk free. Three and a half years ago, when Ali and I discontinued Lyme treatment, I made deals with the universe that, if Ali got better, I’d be satisfied. Acceptance is my mantra. This recent dip of mine is challenging me to use that mantra, rather than dwell on my losses which only increases suffering.

Ali is spending Christmas eve with her wonderful beau, visiting with his family in Albuquerque, experiencing their traditions, planning to bring him back here in the morning for presents and brunch. She has finished 25 of 120 credits towards her degree at U Mass Lowell with a 4.0 average. I am so grateful that she is able to lead a full life – with disability, it is true, but a happy life nevertheless. Finishing this up, I realize I don’t have it in me to go to a party tonight, then walk in the cold for Santa Fe’s Christmas walk with the kids. I don’t want to hold them up or have them worrying about me. I prefer to save my energy for tomorrow. I’m a little sad that I’m not going, but my husband doesn’t seem disappointed, so it’s all good.  It is a glass half empty vs half full moment, sitting by the fire, thinking about friends that are also alone tonight, envisioning a wonderful new year for all of us, filled with peace, love and greater wellerness. Merry Christmas.

Tonight’s song: It Came Upon A Midnight Clear


Our current predicament reminds me of the Jack Kornfield book, After The Ecstasy, The Laundry. Retroviral causation is still a possibility, but what to do after that flash of illumination? How do we circumvent the despair that comes with getting it and losing it again? I catch myself stuck in negative thinking, feeling like I have gained so much insight into the illness, but it came too late for me to do anything “important” with it. After I wrote the last blog, I felt guilty. I mean, after where we’ve been together as a community, who wants to read about watching your diet?

I returned to work still improving, but I’m not any more. In fact, following a couple of back to back bugs that my grandson brought home from his first grade class, on top of several months of prolonged stress, I’m back to pretty definitely sick. Therefore, I’ve decided to take the next 6 weeks to rehab myself, rather than dive off the cliff again next week, when I was planning to make my first trip to Tucson. Magical thinking pretty clearly isn’t going to get me through this time. I need to take my own advice. Physician heal thyself.

What do I want to do differently with this time, besides lowering my energy output for a while and being more consistent with oxygen, diet, supplements, neurofeedback, all of which I’ve done before? For some time, I’ve wanted to try EWOT or exercise with oxygen therapy. I use oxygen to prevent PEM, but I have never exercised with it on. It requires a high flow concentrator (> 8L/min) and a mask with a reservoir that will stay on, but not restrict air flow. There is literature to support the idea that elite athletes (and rats) can do more work while wearing supplemental oxygen, though results have been equivocal as to whether exercising while hyperoxic improves performance in the long run.

I have wondered if it might not also be true that our exercise capacity could be increased this way, we who are on the low end of the bell curve. There isn’t much to go on in the literature, but there are a few papers about exercising with COPD and an oldie but goodie about using periodic hyperoxia to improve exercise capacity in CHF.

And this important paper, that addresses the question of how a treatment that increases ROS in the short term, could be good for us? It suggests that periodic administration, as opposed to long term hyperoxia, enhances antioxidant defense mechanisms, essentially a training effect for the body to fight oxidative stress: Effects of exposure of rats to periodic versus continuous hyperoxia on antioxidant potentials and free radical production in relation to ultrastructural changes in myocardial cells.

Hormesis, a concept from toxicology theory, is a blend of less is more and what doesn’t kill you makes you stronger. Modulation of cellular response by the correct amount of stress encourages plasticity in biological systems. Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders. Calabrese et al. Here is an excerpt from the section “Hormesis, Mitochondria, and Neuroprotection”:

Recent findings have overturned the long-held belief that mitochondrial ROS have only a negative impact on cell function and survival. It is now clear that mitochondrial superoxide and hydrogen peroxide play important roles in a range of cellular functions, and can also activate signaling pathways that promote cell survival and disease resistance…Mitochondrial superoxide production is believed to contribute to damage of neurons in conditions ranging from chronic intermittent cerebral hypoxia to Alzheimer’s disease. However, it has been widely reported that transient exposure of neurons to low levels of superoxide that are converted into hydrogen peroxide can protect the neurons against a subsequent exposure to what would have otherwise been a lethal level of stress. This neuroprotective effect of a subtoxic increase in cellular oxidative stress has been termed “preconditioning” by neuroscientists who study stroke, but clearly falls under the broad umbrella of hormesis… [An] example of trans-cellular hormesis mediated by ROS comes from studies showing that oxidative stress can stimulate angiogenesis in the brain…

Here is another dot to connect:

  • Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients.  In summary, patients with MM show impaired oxidative ATP production in their skeletal muscle, consistent with mitochondrial disease. This study has also shown that increased inspired oxygen concentration improves oxidative function in patients with mitochondrial myopathy, but not sedentary healthy individuals. It is hypothesised that the improvement in oxidative function with increased oxygen inhalation could be the result suboptimal oxygen conductance during exercise.
  • Oxygen Therapy for Mitochondrial Myopathy.  Letter to the editor, so no abstract, but here are excerpts: We report on a physician-patient with a diagnosis of undifferentiated autoimmune disease, pandysautonomia, and mitochondrial dysfunction… Her functional capacity has gradually improved, and her prednisone dose has been substantially decreased for the first time in 8 years. She can now drive around town, walk in a shopping mall, and perform some household chores. In addition, the hair that had previously disappeared from her extremities (thought to be secondary to either the autoimmune disease or medication side effect) has regrown. Prior to oxygen therapy, her soft tissues in the extremities were painful with a boggy firmness, a fibromyalgia-like finding also thought to be part of the autoimmune syndrome. This symptom has gradually, but significantly, improved through a combination of body work (osteopathy and massage) and oxygen therapy. Prior to receiving supplemental oxygen, the same type of body work had been only minimally effective… This case report suggests that supplemental oxygen can enable patients to perform higher levels of cardiopulmonary work with less lactic acid accumulation than room air alone. The use of supplemental oxygen may not only improve functional capacity and certain physiologic abnormalities but may also minimize the mitochondrial stress, which has been postulated to increase the proportion of mutant mitochondria.

I mentioned this paper recently, but it bears a closer look: Normobaric hyperoxia treatment of schizophrenia. It showed that schizophrenics improve sleeping with a nasal cannula at 4-6L/min for 7 hours at night (an uncomfortable treatment). The improvement in symptoms was confirmed by a cross-over design of the treatment and control group. The rat study of periodic vs continuous hyperoxia above suggests that the effects demonstrated in this study might be even more profound with a higher dose for a shorter time. Why would oxygen help this group of patients and what does it have to do with us? Schizophrenia is increasingly recognized as a neuroinflammatory disorder associated with HERV activation. Here is a paper suggesting even more common ground… Antibodies to retroviruses in recent onset psychosis and multi-episode schizophrenia. So, another group of patients who have antibodies that cross react with MuLV sequences, at least in the acute phase.

I wish I could share this whole paper here, because it touches on so many of the questions left in the wake of XMRV. It is well worth a careful read in its entirety: Human retroviral sequences associated with extracellular particles in autoimmune diseases: epiphenomenon or possible role in aetiopathogenesis? Perron. There has been quite a lot of work done on MSRV, a retrovirus, which lies at the interface of endogenous and exogenous retroviruses. Since ME is essentially MS light, MSRV is a good model for us, with a 10 year head start from where we stand right now. Some, but not all MS patients studied express viral particles, which may or may not be infectious. That fits the variable epidemiology seen in our families, where some patients are isolated cases, having never known anyone else with the disease, others have partners and children affected, but otherwise no evidence of being contagious, and there are even a few who believe that they have infected many people through casual contact (food sharing). The idea of recombination and copackaging of viral genomes once again brings to mind the issue of vaccines contaminated with genetic material from animal cells.

As part of the complex ‘biological life’ of such retroviruses, it also appears necessary to study copackaged ERV genomes which may account for their potential pathogenicity by e.g., recombinations or propagation of defective clone expressing pathogenic molecules, and may be at the origin of their rapid loss of infectivity by defective interference and/or ERV takeover. The complexity of retroviral genome studies in these situations, represented in this review by IDDMK in autoimmune diabetes and MSRV in multiple sclerosis, can become a major difficulty for a definite conclusion.

The multiple sclerosis-associated retrovirus and its HERV-W endogenous family: a biological interface between virology, genetics, and immunology in human physiology and disease. Dolei/Perron 

The HERV-W family is one of the most studied, after the discovery of its MSRV founder member (Perron et al. 1989, 1997b). Our haploid genome contains about 70 gag, 100 pro, and 30 env HERV- W related regions (Voisset et al. 2000), but numbers can vary (Mirsattari et al. 2001; Zawada et al.2003); in silico expression data indicate that 22 complete HERV-W subfamilies from chromosomes 1 to 3, 5 to 8, 10 to 12, 15, 19, and X are randomly expressed in various tissues (Kim et al. 2008). Presently, this family is active and generates new recombinant copies in cancer cells (Yi et al. 2004), retains characteristics of functional retroviral envelopes (An et al. 2001; Kim et al. 2008), and HERV-W transposition and retrosequence integration have been evidenced in the human genome through interactions with active LINE-1 elements (Costas, 2002; Pavlicek et al. 2002). Thus, non-Mendelian genetic rules can apply to HERV-W elements: a key feature to understanding their biology.

None of the known stably inserted HERV-W elements is replication-competent (Blond et al. 1999): a study of HERV-W intragenomic spread (Costas, 2002) confirmed that, in the few individuals used for genomewide analysis, the sequenced HERV-W elements lack intact open reading frames (ORFs) in all genes within a single copy. This finding, and the unusual short period of evolutionary time of HERV-Ws (5 million years, estimated on average integration age of different subfamilies), suggested that MSRV might be either an exogenous HERV-W, as in animal ERVs (Palmarini et al. 1996), or a nonubiquitous replication-competent member, or a partly defective but nonubiquitous copy seldom complemented within the HERV-W family (Perron et al. 1997b, 2000; Komurian-Pradel et al. 1999; Dolei, 2005; Serra et al. 2003). Today, though reasonable arguments in favor of the existence of a replication-competent HERV-W member, which might even be ‘‘exogenous,’’ have been provided (Belshaw et al. 2005; Costas, 2002; Perron et al. 1997b, 1992), the very nature of MSRV remains to be confirmed by future studies (Voisset et al. 2008).

They can follow viral load in patients and there is clinical correlation… From the same paper:

A direct parallelism was found between MSRV positivity and load (in blood, CSF, and brain samples) and MS temporal and clinical stages, as well as active/remission phases (Dolei et al. 2002); at MS onset, 50% of CSFs were MSRV positive, and positivity increased with pro- gression. Importantly, MSRV presence in CSF at MS onset was related to poor prognosis; starting from otherwise comparable conditions, after 3 and 6 years mean EDSS (expanded disability status scale), an- nual relapse rate, therapy requirement, and progres- sion to secondary-progressive MS were significantly higher (Figure 2) in patients with detectable MSRV CSF load at onset (Sotgiu et al. 2002, 2006a).

A recent study (Mameli et al. 2008) found that plasmatic MSRV load of naive patients with active MS was directly related to MS duration; longitudinal evaluation of patients during 1 year of IFNb therapy showed that MS progression index (EDSS/MS years) was reduced for the majority of patients, whose viremia became rapidly undetectable. Notably, one patient had atypically high viremia at enrolment and, after initial virus inhibition and clinical benefit, had MSRV reemergence, accompanied by strong progres- sion with therapy failure. The authors concluded that evaluation of plasmatic MSRV could be considered the first prognostic marker for the individual patient to monitor disease progression and therapy outcome (Mameli et al. 2008).

Just published: HERVs Expression in Autism Spectrum Disorders. Balestriere et al, an addition to the growing literature supporting the idea that activated HERVs are involved in autoimmunity, an appealing idea, providing an explanation of why the immune system might become confused as to what is self and what is not. The authors of this paper found increased expression of HERV-H, one of the HERV families implicated in complex chronic disease, in autistics as compared to controls. They also report expression inversely proportional to age and proportional to disease severity.

Our answers lie at the interface of retrovirology, genetics, molecular medicine  and toxicology. The further I go in my attempt to understand the problem on a biochemical level, the less optimistic I am with respect to so called “targeted therapies”. We simply aren’t smart enough and the system we are trying to influence is too complex. This is why therapies that affect the system globally are so attractive. Which brings me back to EWOT. Perhaps the poor, misunderstood Dr. Wessely could let his patients try some oxygen with their GET, now that he says he thinks they do in fact have some sort of a physical problem, in addition to being lazy, crazy and faking.

So, EWOT for ME? I ordered a couple of masks to try. Now I’ve really gone and done it. Set myself up by telling you all about it:). I will report back soon.

Today’s song: Fire And Rain by James Taylor

Recovery post-XMRV

I have a lot to say today and too little energy with which to say it, having just lost ten days of life force to red tape and worry about complying with arbitrary and capricious rules. Between states with differing regulations, plus the DEA which has yet a different set of regulations, I feel like I need a law degree to practice medicine. The system is broken and it is incredibly hard to take care of patients appropriately. When I complained about it recently to a doctor friend in an email, he replied, “My tombstone should read: He died of red tape.” It was always bad, but now nobody even pretends it has anything to do with caring for patients.

My recent month long intensive in Hawaii, treating two young women with ME/CFS and many years of disability, has further convinced me that the therapies I am using are able to tip the balance in favor of a slow climb to wellerness. For the most part, the things I’m doing are not enough alone, but together these therapies are synergistic and additive with continued use. Everything I am doing, and why, is documented and referenced on this blog. The search function in the header works well. The patients are fragile and a lot of tinkering is necessary.

In a nutshell, high dose pulsed oxygen (normobaric and mild hyperbaric) to improve inflammation and mitochondrial function, bioavailable folic acid derivatives for improved methylation (Deplin and folinic acid), sublingual or chewable methyl B-12, Vit D3 replacement, infusions of a modified Meyer’s cocktail including taurine, glutathione by IV push and neurofeedback. Most significantly, I see improvement from weaning inessential drugs, replacing synthetics with bioidenticals, and using herbal treatments instead of pharmaceuticals. In particular, medical Cannabis, if tolerated, for patients who live in a legal state, is a more effective and much safer alternative for chronic pain than opiod drugs, which damage the gut and cause central sensitization over time.

I consider diet to be a cornerstone of treatment. Food as medicine. I advocate a modified SCD diet, allowing whole grain rice, for patients with neuroimmune illnesses that almost always include a GI component in the symptom complex. I encourage SCD yogurt as a probiotic, superfemented to be lactose free and have a high live bacteria count. I also advocate eating organic, and no processed or GMO foods. In particular, avoid the excitotoxins, aspartame and MSG. Here is an important YouTube, by Dr. Terry Wahls, in remission from a wheel chair through dietary intervention alone:

I received some flak for saying that I’m a lumper, not a splitter, with respect to segregating subsets of patients, except for research. From the point of view of clinical medicine, breaking it down into separate cohorts doesn’t help me at all. It is all neuro-immune illness. The therapeutic options are extremely limited. The same things are worth trying in other cohorts also. Many, if not most, of the therapies that are being used in the ASD community are applicable to us. ME is on a continuum with MS and ALS. GWI and chronic Lyme Disease wind up clinically indistinguishable from ME. Fibromyalgia is a subset, not a separate illness. Again, the same treatments are applicable for the same reasons, even if the illnesses look a bit different.

The first thing that happens when there is a response to therapy is improved resilience. A push that would have caused a long crash, doesn’t, but brings minor payback only. At first most everything still feels crappy all the time, though some things have improved. Then some moments that aren’t so crappy creep in. Then some actual good moments. Crappy always comes back though, and when it does, it feels like falling back into the black hole. But it passes much more quickly than before. Improvement needs to be judged in fairly large increments of time, at least 6 months to be sure. One of the young women I treated last month posted this on her FaceBook a few days ago, “I had a good day today; I don’t think I’ve said that in 8 years :)”. That, after only a month of nearly risk free treatment. A long way from a cure, but relief is relief.

Here are some new noteworthy references with respect to oxygen therapy:

I had the pleasure of hearing Dr. Mikovits on Sue Vogan’s radio show, In Short Order, finally able to speak openly in public. The interview is archived here. I thought she was very clear and brave as she answered all the hard questions. XMRV is not a human pathogen. There could be other retroviruses as yet undetected. The mistakes made will inform future research. I personally felt abandoned after the Lipkin paper, subsequent interview by Dr. Lipkin and the press conference, but I am encouraged to hear that he and Dr. Ruscetti are still working on our behalf. They don’t know what the positive serologies mean.  It is tragic that she can’t go back and find out what went wrong so that everyone can learn from it, but much has been learned nevertheless. The only thing she said that I took exception with was that there is no evidence that XMRV has ever infected an animal. Persistent infection has been demonstrated in Macaques after parenteral introduction of virus, exposures similar to what has been happening regularly throughout the history of injected biologicals, dating back to vaccinations with the exudate of cow pox lesions, which certainly contained bovine leukemia viruses, similar to HTLV, and are artificially transferrable to other non-bovine species:

And take a look at this one: Long-Term Infection and Vertical Transmission of a Gammaretrovirus in a Foreign Host Species

So it isn’t XMRV. Other cell lines express other infectious animal retroviruses. Live attenuated vaccines are grown in animal cells that express exogenous retroviruses. Other vaccines contain DNA fragments. Here is the government’s list of vaccine excipients: Vaccine Excipient & Media Summary by vaccine and by excipient. That’s now. The early vaccines were attenuated in live animals. Mouse brains injected into people.

But, say it isn’t an exogenous retrovirus. Why then might antiretrovirals have an effect, in addition to the obvious elephant in the room? The drugs might be preventing transcription of activated HERV’s: Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses.

The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.

Or antiretrovirals, reverse transcriptase and integrase inhibitors, might be inhibiting retroposons:

What makes jumping genes jump? Demethylation.

Reverse transcriptase inhibitors presumably inhibit other viruses besides retroviruses if reverses transcription is required in the replicative process. Viread is used to treat chronic hepatitis B, for example. Hepatitis B is a DNA virus that replicates through an RNA intermediate and uses reverse transcription.

Telomerase is a reverse transcriptase. Therefore, arguably RTI’s might cause faster aging, but might tip the balance away from developing cancer. The more you think about it all, the more you realize that, like all drugs, antiretrovirals are blunt swords with many possible mechanisms of effect, all of which says that clinical trials are in order. One would think that the manufacturers would be interested in new indications for their drugs.

My own illness could be explained by a post polio syndrome caused by an attenuated virus, but it doesn’t fit my daughter. Does an enterovirus explain the vertical transmission seen in our families or a response to  antiretrovirals? Does anyone reading know the answer to those questions? Many of us remember the sugar cube that held the first oral polio vaccine. Polio virus can persist: Transmissibility and persistence of oral polio vaccine viruses: implications for the global poliomyelitis eradication initiative.

Protein from helper viruses and recombination events can rescue defective virus. Innumerable chances have occurred: Science Fiction or Fact? 35 years ago, when I was in medical school, autism and MS were rare. Autoimmunity has skyrocketed beyond belief, as has cancer.

Here’s an unsettling paper. Chemical Induction of Endogenous Retrovirus Particles from the Vero Cell Line of African Green Monkeys. Vero cells are present in the DTaP-Hep B-IPV, Poliovirus inactivated and Rotavirus vaccines. AzaC, one of the chemicals used in this paper is a demethylator. Other methods used in the lab to activate ERV’s and amplify retroviruses in tissue culture are radiation and steroid hormones, bringing to mind the myriad ways in which our environment is contaminated, contributing to the cluster fuck for the genetically susceptible and overexposed. Let’s wrap up today with this article which I haven’t finished yet, but it looks to be well researched: What Is Coming Through That Needle? The Problem of Pathogenic Vaccine Contamination.

 Today’s song: Burn One Down

Life’s A Long Song

It’s been a very strange and unusual three years. The Lipkin study was the closing of the door opened by the Science paper in October 2009. For me, the shift from thinking about neuroborreliosis to retroviral causation for ME/CFS led to clinical decisions that have resulted in great improvement for both Ali and me. We are not well, but we are both leading full and meaningful lives, within the confines of illness. Existing within the confines of illness means the same thing for us that it does for other people with disabilities who need accommodations. It does not mean trapped in endless suffering with no help in sight. Prior to the fall of 2009, Ali and I spent a few really grim years couch bound together, wondering if a quick merciful end wouldn’t be a good thing. Now we are working and going to school. We are even playing some. We need to do it “our way”, but it is happening.

My personal journey through the world of XMRV was littered with betrayal and abandonment, so in a sense, I’m glad that part of it is over. I’m left to practice medicine much as I did before, but with new insight. Three years of reading retrovirology has changed my view of many things, medical, scientific and political. I’m in Hawaii right now treating two young ME women. Much of what I’m doing is a refinement of what I did in my last practice a decade ago. My own emotional adjustment to the collapse of the science involves accepting that the tools I have now are all there is likely to be for a long time. There isn’t going to be a cure and it is a long way off before conventional medicine has anything better to offer than what’s listed on the Mayo Clinic site: sleep meds and antidepressants, which many of us don’t tolerate.  Not even pain meds or anxiolytics. Exercise and therapy, because we are so overly focused on our symptoms. Back on the trash heap.

So where’s the redemption in this story that makes it worth writing about? ME, or ME/CFS, or CFIDS (since I’m a lumper, not a splitter) is a relapsing, remitting illness. It can be coaxed into remission. Remission doesn’t mean normal or healthy. It means not suffering so much. It is a process of encouraging healing and discouraging inflammation, requiring a gentle, multi-pronged approach that relies on synergy, tinkering and luck. Find some maneuvering room, a key for the lock. It is possible to stop the downward spiral, tip the balance and start the slow climb out. Unfortunately, there is never a uniform response to a given therapy with this illness, so treatment can’t be formulaic. When recovery does start, it is slow and fragile. It must be nurtured and it takes years, that from personal experience, since I have only been back in practice for a little over a year. Although, I have heard of spontaneous recoveries many years in, most involve hard work and careful choices. One thing I know for sure. There was never a patient population less suited to medical heroics.

Meanwhile, I sit here in the weird position of being better and still apparently improving on Viread for 2 1/2 years. I was so bad 4 years ago, nobody expected me to do anything productive ever again. Ask my ex-Lyme doc. I had a sleep disorder to rival any of my readers and I know some of you have pretty spectacular sleep problems. I now sleep normally. Even normal dreaming has returned in the last 6 months or so. My gut is also functioning normally on a modified SCD diet, 6 years after emergency surgery for a small bowel obstruction and a Crohn’s diagnosis. My intractable peripheral neuropathy pain, which once required opiates, is now little more than background noise except at the worst moments. PEM is reduced, but still problematic. I can exercise a little, being careful not to overdo, because it feels good in the moment. I won’t list Ali’s symptoms, but she is similarly improved on Viread and Isentress. Her horizons are ever expanding, her illness less and less restrictive. Have we done other things at the same time? Yes. Will antiretrovirals for ME/CFS be studied at all? Not a chance. Our government just spent a couple of million dollars to ensure that ideas like mine stay marginalized.

Dr. Lipkin was quoted on the IMEA FaceBook page in response to questions about whether any “positives” were found, “The investigators reported results as positive or negative according to their own criteria. The only requirement was that once criteria were established results could not be changed through modifications in criteria. I know this is not the intention of those who continue to pose these questions; nonetheless, the impact of this continued challenge to work of the team is that some people in the scientific community who might contribute are becoming reluctant to work on CFS/ME.” Yet, at the press conference, he encouraged us to advocate for ourselves more effectively. So we need to ACT UP, but be nice about it. Any ideas? We are a group in desperate need of effective advocacy. It’s not only the middle aged going down. There is a tidal wave of young people. They are not as visible as their autistic cousins, but just as profoundly disabled. Who is going to care for them when their parents are gone? We need to start advocating for them effectively now.

Life’s A Long Song by Jethro Tull