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The Simmaron ME/CFS Physicians Roundtable Pt. II: Talking Treatments

Round-Table

meeting of the minds picture

Some of the top ME/CFS practitioners had a meeting of the minds on how best to treat ME/CFS at the Simmaron Roundable

Simmaron Research likes to get people talking. At the FDA Workshop earlier this year, they booked a room, invited patients and physicians and then held a physicians round-table with some of the field’s top doctors.

Part II of a three-part series focuses on Dr. Peterson of Sierra Internal Medicine /Simmaron Research Institute, Dr. Klimas  - the director of the Center for Neuroimmune Studies at Nova Southeastern University, and Dr. Enlander, the Director of the Mt. Sinai ME/CFS Research Center talking about chronic fatigue syndrome treatment.

Dr. Peterson – Simmaron Research Institute

Dr. Peterson started off the treatment section with some hopeful news. Powerful new immune drugs such as immune modulators and cytokine blockers), he said, that have been and are being developed, can have dramatic effects in the right patients.

upward slope

Immune therapies under development in other fields may be able to help ME/CFS patients in the future.

(Rituximab is an example of a new approach that paid off. The first of its class of drugs (monoclonal antibodies), Rituximab (Rituxan) opened up a new arena of drug development. Similarly, Ampligen and other Toll-like receptor affecting drugs offer new approaches to immune modulation. Drug repurposing efforts that are finding new uses for old drugs present some intriguing possibilities. An abortifacent, mifepristone, for instance, boosts natural killer cell functioning.

Breakthroughs in other fields are providing other opportunities. Studies documenting the role natural killer (NK) cells and the innate immune system play in preventing cancer have piqued drug developers interest enough the  several NK cell boosting drugs are in development.

A Treatment Philosophy

Some ME/CFS patients, believe it or not, are relatively easy to treat. Patients with easily characterized viral infections have a clear treatment protocol waiting for them. If a parvovirus infection is found, for instance, it can be easily treated. Dr. Peterson has found that the ‘wait and see’ approach so often prescribed by doctors with ME/CFS in hopes that the patient will just get better is a mistake.  He’s found that, in his group of patients, treating aggressively early is more effective.

cascade effect

Dr. Peterson proposes more aggressive approaches to ME/CFS early may forestall problems later if the disorder progresses.

(This brings to mind the story of someone I know whose doctor used a less strong antiviral (Valtrex) for a significant period of time only to switch to a stronger but potentially more toxic antiviral (Valcyte) after his patient deteriorated significantly. The patient then experienced a dramatic and lasting recovery.)

We’ll see that fighting pathogens in ME/CFS is not a cut-and-dried, one-size-fits-all process, and that physicians differ somewhat in their approach. In more complicated cases, for instance, Dr. Peterson is experimenting with combining immune and anti-viral treatments, and thus far is getting some encouraging results.

Dr. Peterson’s use of the antiviral Cidofovir (typically used to fight eye infections caused by cytomegalovirus in AIDS patients) demonstrates how differently even this small group of physicians sometimes approaches infections.

Cidofovir (Vistide)

“Cidofovir is not a panacea for this disease, but I think it demonstrates clearly how we should be subsetting and treating the treatable people,” Dr. Peterson.

Dr. Peterson uses Cidofovir regularly in patients with documented HHV6 and cytomegalovirus (CMV) infections.  (Since he employs more spinal taps than the other doctors at the Roundtable, he probably also finds more HHV6/CMV infections.)

Gunnar Gotschalk

Gunnar Gotschalk, Dr. Peterson’s research assistant, reported on Vistide’s results in ME/CFS patients with HHV6/HMV infections

Gunnar Gottschalk, Dr. Peterson’s research assistant, gave an overview of  the Vistide results seen in Dr. Peterson’s practice. Vistide is an expensive drug with potentially serious side effects that requires a rather complex infusion process.  Most patients need to relocate to the Reno/Lake Tahoe area to get at least 12 infusions.  Once they start the infusions they need to get three blood tests a week.  Vistide is difficult to administer, and its no surprise that most ME/CFS docs are not using it.

Gunnar reported, however, that a retrospective analysis indicated that 70% of ME/CFS patients with HHV6/CMV infections achieved a positive response.  He highlighted three patients: two achieved substantial gains in VO2 max and their viral titers dropped to zero, and all three returned to work after being disabled.

The retrospective analysis indicated significant drops in viral titers, increases in VO2 max (but not to normal) in full responders, and increased NK cell functioning in the group as a whole. Of the full responders Gunnar estimated two-thirds were able to maintain their health and one-third had to restart the treatment after 6-8 months.

When asked to compare Valcyte’s side effects with Vistides, Gunnar said that his experience was that people appeared to have a harder time on Valcyte than Vistide.

CMX001

Then there’s CMX001, the lipid-based analogue of Cidofovir produced by Chimerix that appears to be both more potent and better tolerated and which is beginning phase III (final) trials.

herpesviruses

If CMX001 passes muster at the FDA it will present new possibilities for herpesvirus treatment in ME/CFS

Simmaron believes it has patients that will fit Chimerix’s criteria and is trying to get them into the trials.  (Chimerix, by the way, generated $118 million dollars in gross proceeds when it went public a couple of months ago. Chimerix projects Phase III trials for CMX001 treatment of CMV infections in stem cell transplant patients will be finished in 2015. Since the drug is on fast-track status, the FDA will rule on it more quickly than usual once the data is in). Exactly what Vistide is doing (besides knocking down the virus) is unclear.

On the immune end, it’s possible Vistide is relieving pathogen-associated NK cell dysfunction (although Dr. Peterson thinks more than that is going on) but it’s unclear why the VO2 max readings in his patients go up.  Gunnar did allude to the fact that some deconditioning probably was present in these very disabled patients, but Dr. Peterson thinks cytokine induced mitochondrial dysfunction may be occurring.

HHV6 and Chromosomal Integration

The tricky problem of HHV6 chromosomal integration should be noted. People who have HHV6 integrated into their chromosomes will always, whether the virus is active or not, test positive for HHV6 via PCR. Retrospective studies are never proof of a drug’s effectiveness; you need a placebo-controlled, double-blinded study for that. But retrospective studies do provide the pilot data that could support a trial. (I was told that Dr. Peterson’s Paris presentation generated a lot of interest.) This retrospective study is an instance of a doctor combing through and analyzing their past data, and hopefully we’ll see more of it in the future.

Graded Exercise and Cognitive Behavioral Therapy

“I wish graded exercise and cognitive behavioral therapy worked,”said Dr. Peterson. After mentioning the CDC toolkit (which emphasizes CBT and GET and does not suggest ANY laboratory testing be done) Dr. Peterson said he wished CBT/GET worked, and then said it might be helpful for patients who’ve gotten well enough, but that even if it was, it’s simply not available. For all the talk on CBT and GET, Dr. Peterson knew of no trained practitioners in the US, except for one associated with Dr. Klimas’ clinic.

Dr. Nancy Klimas – Director of the Center for Neuroimmune Studies at Nova Southeastern University

“I’m a splitter not a lumper. I try very hard to find …intervention points,” Dr. Klimas

An  Autonomic Nervous System Focus

Earlier this year Dr. Klimas reported that gene expression tests done during and after exercise suggested that the autonomic nervous system ‘tanks’ first in ME/CFS during exercises, and then drags down the immune system with it.  Her research suggests autonomic nervous system problems trigger an ‘inflammatory cascade’ which then causes much of the post-exertional malaise that occurs in this disorder.

autonomic nervous system

Dr. Klimas exercise studies suggest the problems in the autonomic nervous system trigger problems in the immune system

It was no surprise, then, to hear her say that she spends a great deal of time early on with her patients trying to get that ‘volatile’ autonomic nervous system under control.  (This is an example of translational medicine; i.e., translating research results (gene expression findings) into practical applications in the clinic.) This ANS-immune cascade problem, by the way, appears to be independent of pathogen or antibody results; it’s a core issue present in many patients.

Pathogens and Immune Modulation

With regard to pathogens, Dr. Klimas said most of her patients with high antiviral loads/antibodies will be on antivirals, but generally more gentle ones such as Famvir (famciclovir). She noted, though, that a danger lurks when less-strong drugs inadequately control the virus: it can then ‘break free’ and develop resistance not just to that drug but to others in its class.  A virus that develops resistance to Famvir, for instance, will probably also be resistant to Valcyte. Dr. Klimas then made a plug for controlled clinical trials of Vistide in ME/CFS.

“We don’t really know how to distinguish which group is autoimmune and which group has chronic viral activation”

One has the feeling that the only thing keeping Dr. Klimas, an immunologist, from tinkering more with the immune system in her patients was lack of sufficient data. Referring to the weird immune ying/yang often seen in ME/CFS (some parts of the immune system being over-activated and some parts under-activated), she said she’d love to be able to knock down the immune activation present and build up immune cell functioning, but that building up cell functioning in a patient whose immune system is already overcharged could trigger an autoimmune response. Since no autoantibodies have been associated with ME/CFS, it’s difficult to tell if an autoimmune response is already present.

Some indirect tests can help; high CD4/CD8 ratios, for instance, are suggestive of autoimmunity, and high CD8 levels suggest a pathogen is present. If her flow cytometry tests show high CD4/CD8 ratios, she’s ‘very nervous’ about doing anything to bump up the immune system.

Immunovir (Isoprinosine)

Isoprinosine structure

Dr.; Klimas has had good success with Isoprinosine in ME/CFS

Dr. Klimashas seen an 85% response rate to Immunovir biologically, and it can generally double up NK cell functioning. She obtains pharmaceutical grade Immunovir from Canada Newport Pharmaceuticals and a similar and cheaper over-the-counter preparation called Inosine is available in the US.  Anecdotally she doesn’t think she’s getting as good a response from Inosine. Equilibriant – includes mushroom extracts that enhanced NK function in Chinese studies. Got lots of stuff in there.

Monoclonal Antibodies

A group of patients with extraordinary immune readings; i.e., TNF-a levels hundreds of times above normal, are prime targets for monoclonal antibody drugs (such as Etanercept) that target specific immune factors. In these patients, Dr. Klimas usually brings in a rheumatologist to get the drug.

Expect more news on this in the future, as a great number of monoclonal antibodies coming out of cancer research should be hitting the market, some of which may be able to assist NK functioning. Dr. Klimas said there’s “Some pretty cool stuff in the pipeline”.

“I want to make a plug for Low Dose Naltrexone” Dr. Klimas

Low Dose Naltrexone

Low Dose Naltrexone (LDN), not Lyrica or Cymbalta, is Dr. Klimas’ first line treatment for fibromyalgia-type pain.  A recent study found that it reduced FM pain by roughly 60% without the toxicity of Lyrica and Cymbalta.  She called the science behind LDN (which is not produced in a low-dose form by drug companies but is readily available at compounding pharmacies) ‘riveting’. That’s pretty strong endorsement of an ‘underground drug’ that is getting more and more attention despite its Achilles heel of not being marketed in low-dose form by Big Pharma.

Dr. Enlander – Mt Sinai ME/CFS Research Center 

GcMAF

Dr.  Peterson asked about GcMAF. Dr. Klimas said she hasn’t used it, but Dr. Enlander’s been using it for two years–first by injection and now mostly in his own yogurt mixture. Dr. Cheney probably may have started the GcMAF saga in ME/CFS first with a trip to Italy several years.  A yogurt mix was available, but when one of Dr. Enlander’s patients tried to make it the cost was  $3,000. In the end, Dr. Enlander’s bacteriologists at Mt. Sinai produced the mixture (MAF878) (and at a cost of $120!). Dr. Enlander does believe the injections are probably more effective, but he’s gotten good results for both.

Next Up: the Future! Dr. Peterson started off with hope, and in the next section we take a look at the future for ME/CFS physicians, what their three organizations are pursuing, and what they’re looking forward to in the future.

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10 Comments

  • Issie

    July 26, 2013 at 5:04 pm - Reply

    I found this very interesting and exciting. I have felt that a lot of our health problems relate to the immune system and it’s inability to recognize the things we need to eliminate in order to be well and healthy. (I also suspect that genetics are at play and that is why some may have the weakened immune system to start with.) Many of us have known autoimmune dysfunction problems -(I have hypogammaglobulinemia and yet at the same time my immune system attacks me (vitiligo and alopecia and a positive dsDNA at one point). I appreciate that Dr. Kilmas is recognizing that pathogens could be playing a part in this and that is also true in my case. (I was found to have protomyxzoa rheumaticia and another co-infection associated with Lyme disease – ehrlichia). My doctor – and also the doctor that discovered this protozoa – Dr. Steven Fry- also works on the immune system as the best line of defense in trying to tame these protozoa and bringing the immune system back on track. (Here is an interview of his findings and some of the illnesses that he feels could be connected to the protozoa. http://protomyxzoa.org/wp-content/uploads/2013/04/Protozoal-Infection-Dr-Frye-Interview.pdf ). Dr. Fry has found that the patients that adhere to a low fat vegan diet seem to have the most success with regaining their health. The protocol also involves low dose antibiotics and antimalarial drugs. The main thing is breaking down the biofilms that virus, bacteria and protozoa live in and surround themselves with, a type of protective force field. And then the antibiotics and the immune system can recognize and eliminate that which may be causing so many of our problems. It’s so wonderful that we have doctors who are searching for more reasons why the dysfunction is occurring in the first place and searching for the answers we so desperately need to improve our lives. Thanks to all you pioneering type doctors for thinking in a different direction and not letting those critics, that are always out there, stop you from going in positive directions on our behalf.

    Issie

    • Cort Johnson

      July 26, 2013 at 5:56 pm - Reply

      Really interesting Issie. I’d never heard of that bug before…and I finally learned what ‘biofilms’ are.. (I have to admit I’m a bit gun shy of pathogens after XMRV). How is the protocol and the diet working for you. Are you seeing results?

      • Issie

        July 26, 2013 at 7:32 pm - Reply

        As for how much improvement I’ve gotten. Well, I was in 3rd stage Chronic Kidney disease – I’m now in the upper stage of 2 almost a 1 which is almost unheard of. I’m the 4th patient of Dr. Fry’s that this has had this happen. I’m also starting to have days that my heart rate and blood pressure hardly indicate POTS. I’m finding that the neuropathy that I had in my feet and legs is reversing and I can feel the little bumps in my Crocs now. I have more energy and can stay upright longer. I’m being able to exercise and recover better than before. I’m not having as much edema. I’ve lost some weight – which I wanted to. My fuzzy, foggy, can’t remember anything brain is working most of the time now. My borderline high blood sugar is perfectly normal. All my labs are better than they have ever been. I have no positive markers for lupus now – had a positive dsDNA before. I’m however, still having my immune system attacking me – still problems with vitiligo and alopecia just had a flare with spondylitis. But, for the most part —life is continuing to improve. It’s been 7 months now. He says I’m still in the very early stages of treatment (you have to go really slow, because the biofilm attaches to the vein walls and as you break them loose they could potentially cause a blood clot) and is very encouraged that I’m doing as well as I am so fast. I’m one of his miracle cases. Not all his patients are as determined as I am to do the diet and get better. Some are not mentally in that place and willing to make lifestyle changes. But, I’m very encouraged by my progress so far and intend to stick with the plan. I feel I’m on the right path.

        Issie

        • Cort Johnson

          July 26, 2013 at 7:57 pm - Reply

          Amazing improvement Issie from such a low point… That diiet is a toughie, I must say…But it sounds like its worth a try..

          • Issie

            July 26, 2013 at 9:37 pm -

            I don’t find the diet to be that hard. I don’t look at it as giving up anything. I look at it as a way to improve my life. I’m really only eliminating one food group – animal products. Of course, I have to not have added fat like oil or fatty veggies. That is the hardest thing. It’s not hard being vegan – but a low fat vegan is hard. But, it’s funny – the few times that I’ve messed up with my diet and had too much fat –I’ve felt awful. I realized I was doing that to myself daily and no wonder I felt so bad before. People don’t even pay attention to what we have control over and do daily —-eat. We learn our eating habits from our parents and that has been passed down through the generations. If there is a genetic predisposition of a problem and diet could play a part in that dysfunction —that could explain the problems that appear to be genetically passed on. It’s the one thing WE have control of – and the one thing most people are not willing to make lifestyle changes to. So, it’s not something I’m giving up —it’s something I’m gaining with a positive and encouraging result.

            Issie

  • readyforlife

    July 26, 2013 at 6:41 pm - Reply

    I live in Washington state and have the money to try these drugs, but I don’t have a doctor who will or knows how to prescribe a protocol. I’m on a waiting list to see Dr. Peterson and hope one day I will get the call to go see him. I feel like i’m a classic cfs/me patient that has ebv, cmv, hhv6 and so on. But no one will give anti-virals. I hope something happens soon.

    • Cort Johnson

      July 26, 2013 at 6:56 pm - Reply

      Hang in there readyforlife! It sounds like you’re in the right place and it will just take some time. Good luck :) (I’m not Dr. Peterson’s patient but may be a call to the office telling them, if you can do this, that you can see him quickly if if someone cancels, would work ???)

  • michael

    August 13, 2013 at 12:03 am - Reply

    Pain clinic at hospital keeps pushing their ad hoc piece meal approach to CBT + introductory Mindfulness + very poorly thought through applications of GET (im start exercising then each day do more)…….Australia needs someone to rewrite a thought through response for chronic pain patients as well as CFS/ME/FMS/LYME etc

    That said QUESTION…..Anyone know where one can find experienced practitioners or a protocol to take someone from high level of long term use of strong opioid medications (now tolerant of an ineffective) and go to LDN ? or once you’ve been on options is that no longer an option?

  • Saz

    May 2, 2014 at 1:19 pm - Reply

    We have found LDN and GcMaf to work well we did LDN first for 2 years and got negative ANAs after which did GcMAf.. I wonder why they say you can’t use them both together?

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