Hibernation Consternation

My muse left on extended vacation when the Lipkin XMRV study and subsequent press conference succeeded in discrediting retroviruses as a possible explanation for ME/CFS, with lots of important questions still left unanswered. The discussion reverted to whether or not it is a real disease and which set of diagnostic criteria are best, so there hasn’t been much to inspire me. It got pretty depressing. The IOM report was a joke: “The term ‘myalgic encephalomyelitis’ is not appropriate because there is a lack of evidence for encephalomyelitis (brain inflammation) in patients with this disease…”. Fail. I don’t know what to make of the Lipkin cytokine paper, because I take with a grain of salt results from a debunker on call for the government. XMRV wasn’t the first time: Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. Nothing worth blogging about there. Certainly nothing hopeful. But recently, the Naviaux study was published and a couple of proposals posted by NIH have been making the rounds on Facebook, so I’ve had an uptick in email, some asking what I think about the paper and some telling me about successes with antiretrovirals in Europe, as well as encouragement to blog again. So, feeling very rusty, I’m going to give it a go.

My reaction to the Naviaux et al paper, Metabolic features of chronic fatigue syndrome, was dismay that the damage is so extensive and widespread. So many broken pathways. Finding a specific drug target seems very unlikely. There won’t be an answer anytime soon. They, and everyone else, including Lipkin and Hanson, are studying downstream effects, without attempting to identify the root cause. It’s a good thing that people are thinking and looking, but hibernation and dauer are not disease states and being compared to larval worms isn’t exactly the image change we need ;-). Even if they’re right and a handful of common abnormalities in this very heterogeneous group is accepted as validating real disease, my guess is that the findings will be similar in other diseases, e.g. GWI, fibromyalgia, ASD, maybe even chronic depression. GWI patients have PEM and often meet criteria for ME/CFS. As I said five years ago, I think all of these diseases of modern civilization are related and there is a family factor that confers risk to partners and offspring. There are even a few patients who believe themselves to be contagious by casual contact.

So what lies in wait to be activated by heterogeneous triggers and once activated causes immune dysfunction, neurological disease and opportunistic infections? The most likely explanation lives in the realm between retrovirology and genomics, the difference between the fields being as small as a single mutation. We have been injecting retroviruses and pieces of retroviruses into people for over a century. What are the chances that nothing bad happened from that? XMRV apparently doesn’t infect people, but injected into monkeys, it sets up a low level infection. Retroviruses recombine and rescue each other. Environmental toxins activate retroelements (HERVs and retrotransposons) which can recombine with each other or new incoming retroviral sequences and fully replicative retroviruses from vaccinations, biologics and lab workers. XMRV was created in a lab. The Paprotka paper said the odds of the recombination event that produced XMRV happening twice are infinitesimal. On the other hand, the odds of similar events having happened many times is very high I would think, since there have been so many chances. In the last few years it has been found that many cell lines produce viruses like XMRV which are capable of infecting human cells in tissue culture. Lipkin said in a press conference that 85% of Montoya’s samples contained retroviral sequences and in the XMRV study, 6% of patients and controls were positive for an antibody to SFFV, a very nasty murine retrovirus, but everybody is choosing to ignore those clues because that well is poisoned. Nobody wants to be the next Judy Mikovits. Lo and Alter both dropped it like a hot potato, returning to other research, never mind the question of how all these labs, Mikovits, Ruscetti, Silverman and Lo/Alter managed to consistently contaminate the patient samples at a higher rate than the controls.

Take a look at this paper: Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci by Bjørn et al. “We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response.” They looked at multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. It is one of several recent papers heading in this direction.

I hypothesized way back when that ME/CFS is related to MS. There are case reports of MS improving when patients take antiretrovirals, Multiple sclerosis patient walks after taking HIV drugs, and new cases of MS are rare or nonexistent in patients taking AIDS drugs, HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study.

Our very own Gerwyn Morris published an excellent paper on the subject of ME and MS being related diseases. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. I’d like to take this opportunity to acknowledge Gerwyn’s extraordinary achievement. If you search “Morris Gerwyn” on PubMed, his name appears as an author on 23 papers since 2013, usually as first author.

Lots of evidence has been published about the MS retrovirus, MSRV. Viral particles have clearly been detected, but it is less clear if these particles are ever infectious. There are several new papers reporting findings similar to this one, Two endogenous retroviral loci appear to contribute to Multiple Sclerosis.

Which brings us back to where this blog began. Are retroviruses at the bottom of ME/CFS? Might antiretrovirals be effective for ME/CFS and other diseases? Despite the thorough trashing of retroviruses in our disease and the intense ongoing fear mongering about how dangerous antiretroviral drugs are, apparently people are still trying it in Europe. The experience five years ago, when maybe a hundred people tried various regimens in a completely uncontrolled fashion, was some subjective improvement in about half, and no complete recoveries, except for one notable exception. The exception was a teenager who had only been sick for eight months. His mother wrote in the comments on this blog. He recovered fully, took the drugs for 6 months, stopped and as far as I know, didn’t relapse. I still find it upsetting that the prescribing physician was too cowardly to come forward and write a case report. How many teenagers could have been treated acutely since then? There were no injuries that I ever heard of. I was in touch with many of the doctors who were prescribing and there was lots of sharing, doctors and patients together, the only time I’ve ever seen that happen. One doctor I knew prescribed for 50 patients and concluded that it was better than placebo, but not worth the risk of prescribing it.

However encouraging the Naviaux paper may be with respect to advancing the case that ME/CFS is, in fact, a real and dreadful disease, it is discouraging with respect to finding treatment. A viable drug target seems unlikely. We are left with global strategies, hoping for synergy between therapies that don’t stand alone, same as now. But just as I was feeling dour about dauer…

The NIH compilation of responses to their request for proposals was published here. Read bottom of page 3 to top of page 4. I’m not going to mention any names for Google, because I don’t want to increase the risk of regulatory repercussions against a doctor brave enough to report successes with antiretrovirals. Also please read pages 9-12.

Then I heard from a patient in Europe who is having success with antiretrovirals after 20+ years of illness. In his own words:

I have been ill with ME since my mid-teens in 1994. Onset was in two stages. Firstly a gradual onset, whereby I was feeling increasingly more tested after the combined measleas/rubella vaccine, followed a few weeks later by the polio booster. And then secondly once that prodrome had got its hold, the downward cascade was always inevitable, and just waiting for me around the corner. 1994-2014 were harsh and brutal years. I hovered around 55% on the Bell scale and it was torture enough.

From September 2014 to July 2015 I took tenofovir 245mg. Improvement was an upward curve, albeit with some turbulence. Sometimes taking half- week, or full-week, or month-long breaks when I felt my body needed a rest from it so as to hold its own for a while. From August 2015 to September 2016 I added raltegravir to tenofovir and initially at full dose daily which sent me to sleep almost in the first few days. During this period I toggled around until I found the right balance for me. I got it right in the end around about June/July 2016 and the past two/three months have been great. My current regimen is tenofovir 245mg Tuesday through Friday, and on Tuesday and Thursday I also take raltegravir 400mg x 2. My original baseline was about 55% on the Bell scale for the twenty or so years when I was sick. I am now 95-100% and can go to the gym once weekly thanks to the antiretrovirals where I can build up quite a healthy sweat and recuperate normally. My VO2 max continues to increase substantially and my CD3-4-8 counts are x2.5 to 3 fold what they were before I started the antiretrovirals. Life is very good. I also take celebrex and multivitamin/antioxidant supplements and I am monitored closely.

This year I feel more confident about the winter than I did in 2014 on just tenofovir and than in 2015 when I was grappling with adding raltegravir. They were bad winters even though the arv’s did help me through better I guess. Winter 2016 can throw at me what it wants however. Now that I have hit the perfect treatment regimen with the antiretrovirals I am sure it will be a better winter. It was worth sticking it out and learning. I thank Dr Judy Mikovits and my physician over in Germany, along with the continued support of a rare and dedicated French doctor over there in Paris. Finally I thank two doctors over there in the UK for listening. I salute them all as men and women of true honour.

Several people wrote to ask what happened with antiretrovirals for my daughter and me. Ali and I plateaued without recovering fully. After the initial improvement, there was really no way to know what was happening. We both had a very mild flare of symptoms for the first six weeks and then a noticeable increase in energy and resilience. We started with AZT and Isentress, then switched the AZT to Viread a year later. Ali stayed on the two drugs for three years, not wanting to rock the boat, as she was doing relatively well. I stopped the Isentress after about a year and half and took Viread alone after that. We both improved during the three years we took antiretrovirals, but we were doing lots of other things documented on this blog. Since there was always the possibility that we might do better without them, eventually we decided we should find out. As it turned out, we didn’t decline when we stopped. I had some trouble coming off Viread, because my always labile blood pressure went crazy when I stopped, twice. Go figure. In the end, I weaned without any sort of noticeable decline. When we started, we were all so hopeful. Judy believed we’d be able to monitor viral load in a year, but it wasn’t to be. Our combined copays were breaking the bank and after three years, with no way to monitor and able to stop, it just didn’t make sense to continue. I would consider antiretroviral drugs again if either of us crashed completely.

My experience treating six very informed patients was similar to what other doctors have reported, 50% improved subjectively. Two had adverse reactions to Viread, including one who had responded initially; both resolved quickly when the drugs were stopped. Two patients continued long term, one on two drugs and one who opted for Viread monotherapy. I didn’t see anything dramatic enough to make me very encouraged though. I had successes with other things that were similar in scale with less risk to the patient and the doctor. However, it’s possible that tinkering with lower doses and less than every day regimens would make the drugs we have more useful for ME/CFS, even if they were designed for a virus we don’t have. Although we do not want to encourage resistance to the drugs, it’s possible that a small dose of a reverse transcriptase inhibitor would work for us. I heard from a doctor in Europe who reported complete recovery in 2011 after nine months on micro dose AZT (20-30mg/day). I don’t know how it turned out long term, but will write to him and ask.

Dr. Michael Snyderman is still doing remarkably well, still able to work in his hematology oncology practice at 75, controlling his cancer like a chronic disease, specifically like AIDS. He has been taking HAART for over 6 years, having twice passed his median survival, meaning there was less than a 25% chance that he’d still be alive by now. I will share his data here in the near future. He is still hoping to collaborate with Roswell Park Cancer Center in his hometown of Buffalo, NY to help patients who have cancer and who have a poor prognosis. The same viruses that infect cancers infect the immune system.  If cancer patients benefit as he expects they will, initiatives can be made with the neuroinflammatory disorders including ME/CFS. There is now a reliable virus detection methodology, ViroCap invented by the Wylies at Washington University and the Wylies are interested in collaborating with this research.

These are leads, the only leads we have. If drugs developed for a completely different retrovirus have some activity against a disease, think what could happen with some attention to the process that is actually occurring. The technology, next generation sequencing, already exists to begin to answer our questions, but the various software platforms that analyze the data are still in their infancy. The metabolomics studies are happening because there is a new toy. There are going to be lots of new toys in the near future. It already didn’t happen by random doctors prescribing off label. Since it wasn’t a slam dunk, it needs to be formally and properly studied.

It is possible that the metabolites that Naviaux et al have identified as a potential diagnostic panel might be useful for monitoring success with antiretrovirals. Dr. Naviaux has answered questions here, stating that he thinks the use of antibiotics and antivirals aren’t indicated and I mostly agree with him, planning to share my thoughts on treatment in a future blog.

I continued to go slowly uphill after I last blogged about ME/CFS almost two years ago, but nothing like a full recovery. I was able to work a little and I was able to ride on the back of a tandem, close to a thousand miles in two years according to Strava, half of it on dirt. Still lots of symptoms, but a life, where once there wasn’t one, plus a way to get endorphins. My recovery was slow after exercise; I felt drained the next day, but nothing like full blown PEM. I was still maintaining the fantasy that someday I would recover fully. But a year ago, while hiking, I twisted my ankle and broke my distal fibula. It was a minor fracture that should have healed without problems in 6 weeks. Instead I got RSD/CRPS (reflex sympathetic dystrophy/complex regional pain syndrome), a very challenging and painful condition. It takes most of my energy just to cope and I’ve been out of commission since it started, able to attend only to my own treatment (HBOT).

After 5 years of managing patients, I had to retire completely. I only worked with a very small number of patients, scattered all over the country, who saw me in person once a year in Hawaii or Arizona, but I got to know them very well, because most of the contact was electronic, day to day, moment to moment even, and that works well for ME/CFS patients. It was enough to learn quite a bit about the spectrum of disease, what works and what doesn’t, especially given that almost everyone I saw had been around the block and came with voluminous records, having failed treatment with the best. I’d like to share my impressions while still fresh, so intend to keep blogging, if I don’t get too beat up over this one ;-).

Today’s song from Les Misérables

Cactus Fruit

Last October, after three months on the Wahls paleo diet, I recovered my ability to benefit from exercise. I had been unable to exercise without payback for nine years, since starting treatment for tick borne diseases, a decade into my illness. That most intangible switch between can’t and can suddenly flipped back and aerobic exercise became possible again. No drugs involved. Just a clean, nutrient dense, low carbohydrate diet. Lots of healthy fat.

In February, the “flu” went through our house. I was down with it for about 6 weeks. Then I pushed through and went to Tucson to see patients in April. My upper respiratory tract symptoms came back on my second day home and a week later my husband got sick also. Then, in quick succession, I had a UTI, sinusitis and a salivary gland infection requiring back to back courses of antibiotics.

My mood crashed also. It’s really tough to be very active for a while and then find yourself back in the pit. When I was emerging from years of hell, I felt amazingly wonderful, even though I still had lots of symptoms. Conversely, after a period of very few symptoms, I had a lot of trouble coping with symptoms that would have been no big deal when I was sicker.

I don’t usually catch stuff. I’d been experimenting with higher doses of Vitamin D after reading some studies about using higher doses in MS patients for anti-inflammatory effect. In hindsight, the dose I was taking was probably too immunosuppressive for me, though it is cited as safe in several recent papers. When I went back to a lower dose, the infections stopped. I didn’t try this experiment on anyone but myself. If you do try higher doses of Vitamin D, follow levels and be careful. Upward target level creep is happening in the literature, as people try to use Vitamin D as a drug, not just a preventative. For me, 5000 iu daily seems OK and my 25(OH)D level on that dose is about 50 ng/mL. More was not better, but I am not saying that it couldn’t be for someone else. The word isn’t in yet as to how to supplement Vitamin D optimally in the setting of neuroimmune illnesses. Natural sunlight is no doubt the best way. The most powerful ways to heal are provided by Mother Nature, not a pharmaceutical or neutraceutical company.

Despite my fear that the gig was up for good this time, gut torn up again by antibiotics, I started the climb back to wellerness. I was really weak when I got back on the bike, but I improved faster than the first time and by early August had surpassed my previous level. Anthony and I spent our 26th anniversary camping on the Conejos River in southern Colorado, and went fishing in our canoe on Platoro Reservoir, same as our 25th. Last year, I needed a special seat on the floor of the canoe with a backrest. This year, I could help paddle. Last year, I couldn’t ride a bike. This year, we rode uphill on a fire road for an hour, from 9000 to almost 11,000 feet, before a long, exciting descent. Then later, the same day, we went fishing. If you have been reading my blog for a while, you will recall, I used to need a wheelchair to get through an airport. Now I could jog to the gate if I were late. Exercise is my go to “treatment” when I am feeling poorly, which I still do, not infrequently. I am not cured, by a long shot, but I’m not at the mercy of the illness. I can fight back.

I still attribute my recovered exercise ability to the Wahls paleo diet. I’m no longer completely adherent though. My intake of vegetables is much increased from prior, but I’m no longer force feeding. I eat some rice and quinoa and a few legumes. I eat bananas, apples and pears, though Wahls excludes them. I’ve learned that any dairy is problematic, except butter, but I can get away with a bite of gluten, at least as far as I can tell. Properly produced eggs are my friend, though I haven’t tested for egg allergy or tried eliminating them. My focus has become not only what I eat, but what I avoid, especially toxins and GMOs. We are paying attention to what cookware we use and what we store food in. Bone broth is a staple in our household. My daughter makes it with fresh turmeric root and seaweed. I love my green drinks. We are having an adventure with fermenting. We are learning what edibles grow naturally around us. I am going hunting for prickly pears with my daughter and grandchildren in a little while, planning to make prickly pear, crabapple butter. It will probably be terrible:-), but the walk and the project will do us good.

We are no longer eating as much meat as we were when we first went on the diet. We are a large family and bought a whole cow from a local ranch. It was definitely different to buy it alive and sign off on its slaughter. For about six months, we ate a large amount of very high quality, grass fed, grass finished beef. After that, two healthy members of the family had serious GI complications, specifics of which I won’t share to protect their privacy. Anecdotal of course, but we decided to back off on the red meat. We are eating more fish, even though finding clean fish is so problematic, and having more vegetarian meals.

I stopped writing, not because I was too sick, but because I was too negative. Existential crisis. Jaded and cynical. Disgusted with how broken and corrupt the system is and how hopeless it seems that our current suicidal trajectory can be changed in time. We are about to be a failed experiment, on a global scale. Why write about it? Time to eat, drink and be merry. We have the technology to figure out what we need to do, and not do for neuroimmune illnesses, but no cavalry is coming over the hill. The game is rigged. All greed and special interests. What gets studied, and then published, is tightly controlled. Obvious studies that challenge a prevailing paradigm will not get done (vaccinated vs unvaccinated children or the family study we tried to do once on this blog). Scientists who dare to depart from the mainstream paradigm are discredited (Mikovits and Ruscetti). Yet real live fraud within a government agency that most likely harmed children is covered up by the media (see my last blog). The billions of dollars paid out by the drug companies for their frequent gigantic frauds make the news, but their stock prices remain strong. Those billions are just the price of doing business. And they are indemnified in the case of vaccines, so that’s a real gravy train. The medical profession is completely asleep at the wheel when it comes to the causes of or solutions to complex chronic diseases. Safe treatments that can’t be patented, like home oxygen, will never be studied. So their treatments now do more harm than good. Conventional doctors push dangerous drugs. Alternative doctors push expensive tests and supplements. Depressed yet? I certainly am, if I think about it too much. So I won’t. I’ll go on a hike with family at the end of a magnificent monsoon season in the high desert, pick prickly pears and be grateful I can walk. Time to find some heavy gloves.

Stay tuned for an update from Dr. Michael Snyderman.

By Way of Sorrow –  Cry, Cry, Cry

Opting Out

My thoughts keep coming back to this paragraph on the CFS Patient Advocate blog:

Mady Horning gave a fine talk, echoing the one she gave in Florida in January. That talk can be accessed here. She spoke of the terrain and genetic defects leading to ME/CFS – what variables contribute to getting ME/CFS. In a follow-up question she was asked what we all want to know. What information can she give about the ongoing CFI Lipkin study? She said that 80% of the blood work is done, but that much additional work needs to be done on saliva, feces and urine. She said that they had identified several promising pathogen “candidates” including a “novel pathogen” – but the work was still early and no conclusions can be drawn. I have heard the term “novel pathogen” somewhere before.

A novel pathogen from Dr. Lipkin’s lab… Hard not to speculate on what it could be. An attenuated poliovirus perhaps? That would put us back into the doomsday scenario, life imitating science fiction again. My illness is consistent with a post-polio syndrome. I received the very first round of the oral polio vaccine from my pediatrician father. I have a vivid memory of lining up with the kids in his practice to get my sugar cube. I remember impressive pain from IBS for some time after that. My father told me it was normal, but I wonder if he wondered. He knew the state of the technology. My father’s office was attached to our house. He had rats in the toolshed on which he did research.  I also remember getting called into his office to get a gamma globulin shot followed by a kiss from a patient with measles, so I would get a “modified” case. He was on the frontier. Rockefeller Institute was nearby.  Lots of women exactly my age (59) are sick. Too high a percentage of the patient group. It was a wave. Something went out horizontally. There were other waves, the first outbreak of Epidemic Neuromyasthenia at LA County Hospital happened two years after the Yellow Fever vaccine was released, a live attenuated vaccine passaged through mouse brains, mouse brains that express viruses like XMRV. Maybe it’s a persistent enterovirus, as Dr. Chia has long thought. Maybe it lies dormant, and with an appropriate trigger, say organophosphate exposure, mold, infection, trauma, vaccination, what have you, it fires up and activates HERV’s, probably different sequences in different people and families. Doesn’t fit as well as the retroviral hypothesis, but it could be right.

Yes, I find myself hoping against hope that “the world’s most celebrated virus hunter” will find our pathogen(s). We need new treatment strategies. We are becoming visible as a patient group and there is more acceptance that there is a biological basis for our illness. ME patients are demanding the big guns. We are going to get what other patient groups get, to be guinea pigs. This is what can happen: PML Case Seen in Patient on Gilenya. This was an MS patient. PML or progressive multifocal leukoencephalopathy is a complication of drugs like Rituxan, trials currently being sought by ME advocate groups. That’s what modern medicine has to offer you, if you have a real disease.

Not to mention how monoclonal antibodies are produced… Hybridoma technology involves producing cells that are a fusion of another mammal’s B cells and human cancer cells and the resultant product is introduced into humans. Revolting when you think about it. Probably just the sort of thing that got us into this mess. Splicing and dicing viruses and growing them in the cells of various animals. That’s where XMRV came from. How many more? Here’s another scary one: from Modelling the long-term persistence of neutralizing antibody in adults after one dose of live attenuated Japanese encephalitis chimeric virus vaccine, which says, “One such new vaccine is a Japanese encephalitis chimeric virus vaccine (JE-CV; Imojev™; sanofi-pasteur), a live, attenuated product grown in Vero cells.” Vero cells are monkey kidney cells. So viruses spliced together in the lab and grown in monkey cells, which can express viral particles, are injected live into people. “Attenuated”, meaning reduced virulence, which doesn’t tell us anything about whether a virus persists or not. They look for persistence of antibodies, but not for persistence of the live virus they intentionally infect people with. Look how much they knew about the dangers of using monkey cells in 1960: Notes on viruses likely to be encountered in vaccine production using monkey kidney tissue. The government acknowledges that 30 million people were accidentally innoculated with a monkey virus, SV40. Not so surprising given the crude techniques they used at the time. It Only Took 50 Years: CDC Admits Polio Vaccine Tainted with Cancer Causing Virus.

It is out of control. Biotechnology run amok. We don’t have the wisdom, individually or collectively. It is all built on a faulty premise, that Big Pharma is going to save us. It isn’t going to happen. These are the folks that brought us Viox, Avandia and Fen-Phen. Fraud is rampant in the pharmaceutial industry. Huge multibillion dollar settlements happen all the time. Our world is becoming populated with sick people. In the US, 55% of children have a medical condition, 20% of the population have a rheumatologic disorder, 2% of children fall on the autistic spectrum. 1% of the US population has ME/CFS. MS, cancer, neurodegenerative diseases. The disease burden is enormous and completely out of balance with nature. It is no doubt multifactorial, but the parenteral use of engineered biologicals must be high on the list of stupid things we have done. All of this interspecies tinkering and regular introductions of foreign DNA and RNA into people who are chronically inflamed from their environments anyway, has offered innumerable opportunities for the creation of new infectious viruses. It is ridiculous to think that the creation of XMRV was a unique event.

The older I get, the clearer I am that pharmaceuticals are a very poor answer to chronic illness. All drugs are poisons, which doesn’t mean that you might not choose to take one, but they are almost never truly health enhancing. In particular, drugs which are akin to shooting a bazooka at the immune system are a bad idea. I know, I know, I am taking antiretrovirals. However, I have every reason to believe they are not going to kill me. I do not know if they are helping or not, but I tried to stop them and got worse. I had a prolonged hypertensive crisis when I came off Viread, requiring the addition of more drugs, now getting back to my baseline after on again for 6 months. Thus, I think I am better back on Viread and Isentress, but how can I know for sure? The disease waxes and wanes all on its own and life happens, making it very difficult to evaluate the effect of any one intervention. Antiretrovirals are not the only thing Ali and I do for our illness. We use oxygen and methylation supplements. We are always working on our diet and supplements. We get ever cleaner about food and the products we buy. Life does not imitate science in any way. Real life is always multifactorial.

At any rate, almost 3 1/2 years in, despite huge stress in the last 2 years, Ali and I are still beating the odds. We are not well by any stretch, but it’s a good life. Still improving glacially, not all the time, but overall, better function. Able to do more with less payback. Minimal suffering compared to our years as chronic Lyme patients. I have never said that anyone should take antiretrovirals, but it is still unfathomable to me that it has not been studied at all. Enough people experienced initial improvement, though it was rarely dramatic, and often didn’t last beyond a year, but it is a clue. These drugs are supposed to have specific activity and weren’t designed for what we have and yet, they can have a positive effect. There has still been no experience at all with protease inhibitors, except as reported to us by Dr. Snyderman. I don’t understand what it is about this particular class of drugs that freaks everybody out so much. Patients get  much more dangerous drugs for much flimsier reasons every day. Why? What’s the big deal about a trial of drugs which inhibit retroviral proteins, especially since they might have an impact on activated HERVs or other retroelements. I don’t understand why the drug companies aren’t more interested. There are more of us than AIDS patients. Throw in ASD and MS, we are talking about a lot of people.

My first day of medical school, in 1975, a wise professor told us, “Half of everything you learn here will turn out to be wrong.” Well, it was much more than half. Just recently there have been papers reporting Zithromax can cause sudden death. Statins and beta blockers are bad for old people. All those CYA  head CT’s we did on little kids that we knew would be normal gave some of them brain cancer. Mammograms are bad for you. When it came to nutrition, they didn’t teach us much of anything, but what we did learn was wrong. Turns out diabetics don’t need to limit fruit, only refined carbohydrates. Vegetable oils are mostly bad for you. Salt, coffee, bacon and eggs are good for you, if properly sourced. “They” were wrong about almost everything. What is bad for you is to eat processed foods that contain genetically engineered plants that tolerate RoundUp, but have almost no nutritional value.

What is bad for you is to take drugs for symptomatic relief of chronic symptoms. Sleep and pain meds are a trap. They commit patients to a kind of purgatory. They cause poor quality sleep, depression and cognitive decline. Deadeners. They lead to physical dependence and tolerance is an ongoing struggle. I am not judging anyone. I did it. I call them my lost years. Everything improved when I discontinued antibiotics and medication for symptom relief. I wish the drugs really helped, but they don’t, and they make it worse over time. Don’t kill the messenger. I prescribe them if I have to, but my patients know going in that my agenda is to wean them if at all possible. When patients give up unnecessary drugs, they come out improved on the other end, pretty much without fail, because the body works better without the toxic assault. I know up close and personal what it is like to sit there on pain meds, not tolerating the pain, wondering how it is possible to survive without dulling it, but the brain has been sensitized to the pain and in fact, can’t adjust to the reality of the pain while the drug is there.

Sleep is such a fragile thing. There is no way to reach deep restorative sleep through artificial means. Insomnia is perhaps the hardest symptom to address, inflammatory in nature. Insomnia goes hand in hand with better or worse, in a chicken or egg fashion. Melatonin and herbal concoctions can help. Neurofeedback may help, though sleep disruption is a stubborn symptom. Sleep hygiene is crucial. Sleep returns with wellerness. It is important not to go more than one night with no sleep, but sometimes some sleeplessness may have to be endured to get the body used to not being knocked out with drugs. There is a payoff at the end of that tunnel. Please note, it is dangerous to stop benzodiazepines without weaning.

Our family is trying hard not to comply with Big Ag’s agenda. We are a big family. Four generations under one roof, and I am blessed to be living with young adults who share the work. Ali and I are following the Wahls Paleo Diet, the rest of the family also, plus some rice, potatoes and gluten free bread. We both really like it, though Ali just discontinued Actos, after a slow wean. It was kind of tough every time she went down, so she hasn’t realized a tangible benefit from the diet yet the way that I have. She was already on the best diet of all of us. She plans and prepares many of our meals, for up to 9 people, a clear sign of how far she has come. I’ve been much less symptomatic since I started the diet. I was away for 5 days of wilderness camping with my husband for our 25th anniversary, didn’t have my daily smoothie or as many veggies as at home, cheated with a little gluten free bread, and my gut noticed. Now home again for 4 days, I again realize how important this diet is for me. What surprises me is, our diet was already really good. The differences are a huge increase in fruits and vegetables, no grains (we had already eliminated gluten), grass fed/grass finished animals, more fish, seaweed, marrow bone soup, nut milks, no cheese (we were already non-dairy except cheese), all organic, completely non-GMO (we were mostly there already). We are also emphasizing fermented foods, including brewing our own kombucha. Today’s smoothie was spinach, kale, purslane, frozen berries, hemp seeds, coconut milk, glutamine and water in the Blendtec. I used to be anorexic until noon. If I drink a veggie berry smoothie in the morning, my appetite is improved for the whole day and I can eat lots of green things.

Please read the comment by Celia Harrison in the last blog. There are other testimonials on the internet by ME patients who are finding this diet beneficial. It is likely useful for all neurodegenerative diseases. I heard from people who took exception with my use of the nickname MS Light in previous blogs, feeling that it trivializes our illness. That was certainly not my intent, rather I think the comparison of ME to MS is a useful one conceptually, but sister illnesses is a better way to put it.

It is more than a diet for us. It is a complete lifestyle. We are buying our food from local sources. No convenience foods. We are gardening and planning to expand next year. CSAs (community supported agriculture) are a wonderful way to go. Organic produce, in season. Instead of shopping for what you want, eat what you get. Big Ag considers the food we are eating specialty crops, because they don’t generate big profits. They don’t get made into GM corn syrup, which is what they make their money on. They have been feeding us their insane ideas, e.g. food containing BT toxin. Our illness is part of a bigger problem. The bees are dying. They are canaries in the coalmine, just like we are. The ways in which food is being mass produced in the modern world is making our planet sick also. What a strange world that growing your own vegetables and supporting local farmers is revolutionary.

Opt Out


Today’s song: As Time Goes By

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. ClinicalTrials.gov 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 going..to avoid the failure of Hemispherx..we have a huge opportunity here..talk 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

Now You See It, Now You Don’t

The Lipkin study buries XMRV once and for all, completely leaving aside the question of an infectious chimera out and about that contaminates a clean lab in a matter of days and is capable of infecting monkeys. But it wasn’t in the blood of the patients or controls in this study. That much is clear, forgetting the unscientific claim that this study, or any study, is definitive of anything. Science is self-correcting, as Dr. Lipkin reminded us, but only if the game isn’t rigged. This is a repeat performance of the definitive study that showed that the MMR doesn’t cause autism, which also side-stepped the bigger question. The use of the word definitive tells us we are dealing with politics, not science. Sleight of hand.

The paper didn’t even try to speculate as to the one positive finding, that 6% of the study group, patients and controls, cross reacted with a test designed to detect SFFV, a nasty murine retrovirus. Whatever it is they are picking up with this serology test, “modified slightly” from the one once used at the WPI, the various PCR’s used in this study, optimized to detect XMRV and a piece of a “generic” pMLV, couldn’t detect it. But that doesn’t mean it isn’t there.

A young friend emailed after watching the press conference asking that I blog because my blogs are hopeful. I’m not sure how to spin this as hopeful other than XMRV got us into national news as having a real disease. It’s good that there are people studying us, even if they are abandoning the hypothesis of best fit. So, as my friend asked, do we still have retroviruses? The answer is everybody has retroviruses. 8% of the human genome consists of retroviral sequences. It is becoming accepted that these sequences are capable of causing trouble in some people, whether they produce fully replicative virus or not. SFFV is a replication-defective virus that causes disease in mice: The spleen focus-forming virus (SFFV) envelope gene, when introduced into mice in the absence of other SFFV genes, induces acute erythroleukemia. S Ruscetti

The Lipkin study in no way disproves the hypothesis that simple animal retroviruses, alpha, beta and gamma, parenterally introduced, in the form of vaccines and from other sources, e.g. hybridomas, xenografts, etc., have recombined and rescued defective endogenous retroviruses, and/or created new and as yet unrecognized exogenous retroviruses. The existence of XMRV, is supportive of this theory. There have been so many chances for it to happen, in addition to the possibility that it happened naturally. This means that we each may have something a little different. Which is why they can’t find “it”.

Personally, as a defender of Dr. Mikovits during this entire mess, I appreciated Dr. Lipkin for openly defending her struggle against the Whittemores. The scientist who put the nail in XMRV’s coffin. Dr.’s Mikovits, Ruscetti and Alter completed the difficult task of acknowledging they’d been mistaken. Our disease has finally been deemed “serious and life threatening” to enable fast tracking of drugs, should there be any drugs worth fast tracking, which seems unlikely if nobody is studying the root cause of the disease, only looking at downstream effects.

I’m not even going to question the study design, patient selection, specimen handling, that the patients chose their own controls, etc. I accept at face value that Dr. Lipkin put together a convincing study in order to put the final nail in the coffin about XMRV. No surprise there. I assumed the study would be negative. But I expected the authors to have the intellectual integrity to state that ruling out XMRV does not rule out retroviruses. Instead they allowed the press to distort in predictable ways. I therefore must conclude that Dr. Lipkin plays for the home team. His task was to kill it and reassimilate the renegade scientists into the group. To make sure that nobody does any clinical trials of arv’s, the paper suggests that the patient community has been saved from that terrible fate by this definitive paper. Mikovits’ name right there with Coffin’s. Task accomplished. But even Coffin said that it might be another retrovirus. Smart people allowing distortion and partial truths. It looks to me like we’ve been thrown back on the trash heap. From the Wall Street Journal. Viruses not to blame for chronic fatigue syndrome after all. Thank you Mr. WSJ editor for that headline, suitable for a tabloid.

Why do I still believe retroviruses are involved in causation in the face of so much evidence against XMRV? Even though we don’t have XMRV or active replicating virus with some certain degree of sequence homology to a piece of a “generic” pMLV, retroviral causation has not been ruled out. It is still the best explanation for all of the observed phenomena. It works as a clinical model to explain the symptoms and put treatments in context. It even explains the obvious but still unstudied epidemiology. Dr. Mikovits was trying to sequence what she believed were positive cultures that were negative for XMRV. She sent out letters to that effect to patients.

Then there is the response to antiretrovirals. Dr. Snyderman has presented amazing data, that most of the scientists involved in this story have seen and ignored. He has not been cured, but his leukemic cells and his cells capable of making cytokines have decreased with treatment. Cancer treated like a chronic disease, like diabetes or AIDS. I don’t think they are stupid, so they don’t want to know. Why not?

If the response of longstanding ME/CFS patients to limited arv’s (RTI’s and II’s alone) had been more robust, we wouldn’t even be having this discussion. It wasn’t. There were early responses that were encouraging, but with no way to follow, after a while, you’re left not knowing what is happening. Meaning we don’t know how to use the drugs, not that they have no value. Maybe they should be pulsed or given low dose for N chain termination. Maybe a protease inhibitor is necessary for full effect. Dr. Snyderman is documenting an ongoing response to Kaletra. The best case we heard about anecdotally was a teenager, hadn’t been sick long, responded fully and the drugs were stopped at 6 months, remaining well as far as I know. It is beyond sad that this case was not published. While new teenagers get sick with an “untreatable” disease, they are denied a trial of very safe existing drugs. It could have been studied for a lot less than the 2 million dollars spent to prove it isn’t XMRV.

I have tried to discontinue Viread on three occasions, since our drug co-pays are a problem, and I haven’t been able to do it. I get sicker within days and feel better quickly after restarting. Can I prove it? No of course not. The disease is a relapsing remitting illness all on it’s own. However, I didn’t have trouble stopping AZT or Isentress. I have been under enormous stress since June, with one thing after another, one of those times in life when the waves just keep coming, too close together for recovery. I am a little worse than I was, but only a little. I’ve even been able to ride the tandem a couple of times recently, only 5 miles on the flat, but no PEM after. Ali continues to do extremely well on Viread and Isentress. She has considered stopping arv’s, but has decided not to rock the boat at this time, since improvement seems to be continuing very, very slowly. The possible downside besides financial? I don’t know of any for Ali. I’ve aged a lot in the last couple of years, though it is on time, coming after a late menopause, so I can’t really blame Viread for that. I heard from a patient yesterday who did well on AZT, Viread and Isentress for a year, but then went back to baseline for another year with some new symptoms that could have been drug related, though hard to know. As I said, we don’t know how to use these drugs. We have no way to monitor. That doesn’t mean they have no value.

But Dr. Lipkin told Dr. Racaniello:

I know some in the community –the scientific community—feel that this was not money well spent, but the fact is, I think that we have obviated a lot of, you know, missteps that might have followed with clinical trials and such for antiretrovirals. And in addition, we have been able to establish a sample bank that will be helpful for years to come. And we’ve been able to hold, I think, the attention of the community.

So Dr. Snyderman, Ali and I are missteps…

From the 3rd paragraph of the paper:

Since the index publications, clinics have been established for the treatment of ME/CFS with antiretroviral drugs…

This is a complete fabrication. Where are these clinics?

It is completely incorrect, and unscientific, to conclude anything from the Lipkin study other than they didn’t find XMRV or a particular pMLV sequence. That’s a long way from no viruses or even no retroviruses in CFS. How is it that 2 million dollars was spent to tell us what we already knew a year ago? No reproducible assay. 2 million dollars and all that effort to prove what isn’t. For three years, we’ve been waiting for the scientific community to run with the ball. Now it is pretty clear, the ball has been dropped, while they huddle to congratulate each other on a job well done. The status quo is restored.


Today’s song: Who’ll Stop The Rain by Creedence Clearwater Revival

We Must Move Forward by Michael Snyderman, MD

Dear fellow patients, physicians and scientists:

The quest for identifying and treating retroviruses that are involved in the pathogenesis or CFS/ME, neuroimmune, autoimmune and neoplastic disorders will not end today despite the negative results of the XMRV, pMLV study. I have CFS/ME and cancer. My data supports the presence and importance of retroviruses in the pathogenesis of both disorders and the potential for anti-retroviral drugs to help us.

My data shows the presence of a clonal T-lymphocyte expansion which is probably CD8 cells. Having a clonal T-lymphocyte expansion is abnormal.  In addition, I have increased monocytes (monocytosis). I have looked at 56 of my patients with various types of cancer and half of them also have a detectable T-lymphocyte expansion and monocytosis. My point is that what I see in myself may be a common phenomenon and actually may be happening in millions of people. I haven’t looked in CFS/ME, because I limit my practice to Hematology-Oncology.

T-lymphocytes and monocytes are important because they are permissive of retroviral invasion and because they are pre-programmed to make cytokines. Presumably the increased numbers of these cells after infection has occurred would lead to increased amounts of cytokines that would dysregulate the immune system. In addition, monocytes give rise to the microglial cells which migrate to the brain and spinal cord and potentially could deposit abnormal amounts of cytokines in direct proximity to the neural elements.

Dr. Lipkin mentioned a polyclonal expansion of B-lymphocytes as important in our type of disorder and this could be a result of the increased amount of cytokines. In fact, in my patients who had a clonal T-lymphocyte expansion and/or monocytosis, 50% had autoimmune markers. What is reasonable to postulate is that we now have explained the known connection between inflammation and cancer and neurodegenerative disorders and it all goes back to the retroviruses.

I have previously shown response of my leukemia, monocytosis and clonal T-cells to AZT, raltegravir and after relapse a second response to the addition of tenofovir. I had hoped to demonstrate that a PI would be valuable treatment and waited to add this category of drug until relapse. My leukemia responded and relapsed in parallel with the monocytosis and clonal T-cell expansion but at a somewhat different rate.

The last graph shows that the clonal T-lymphocytes, CD8 lymphocytes and monocytes were increasing after relapse on AZT, raltegravir and tenofovir. Quest discontinued doing the quantitative TCRγ in 2011. As a favor to me, Quest put it up but with different reagents so that the results from the new assay are not superimposable over 2011’s. Please note that the clonal TCRγ values are a ratio rather than an absolute number of cells.

I didn’t have the new clonal T-cell assay available until later in the graph and didn’t think of looking for CD8 cells initially. After the relapse was clearly documented, I added the PI, lopinavir. The T-cell parameters and monocytes continued to trend up for the next 4-8 weeks before clearly trending down.

The only reasonable explanation for what has happened to me and what I have found in half of my cancer patients is that retroviruses participate in the pathogenesis of our illnesses. Please note that I do not claim that the retroviruses cause the illnesses but emphasize that the retroviruses participate in the pathogenesis. The likelihood is that genetic susceptibility and toxic exposure determines whether an infected person would develop disease and how it would be manifested.

It is clear to me from the data I have, that many people have susceptibility to develop disease after infection with retroviruses. It is now up to the scientists to identify the infection and the basis of genetic susceptibility. Once there are easy methods to identify who is infected and with what, treatment trials could be started. We must go forward.

Michael Snyderman, MD


Click figures to enlarge