4 Immune System Modulators

From: 'Chronic Fatigue Syndrome, A Roadmap for Testing and Treatment' <a href="https://sites.google.com/site/cfstestingandtreatmentroadmap/home">https://sites.google.com/site/cfstestingandtreatmentroadmap/home</a>
These are drugs and supplements that modulate (modify) the functioning of immune system. Some immunomodulators used in ME/CFS shift the immune response from the Th2 mode to the Th1 mode. There is evidence that ME/CFS patients are stuck in the Th2 mode, whereas they should really be in the Th1 mode, because it is the Th1 immune response that fights the viruses and intracellular bacteria linked to ME/CFS.<a href="http://wayback.archive.org/web/20101214023010/http://cfids-cab.org/cfs-inform/Immunology/patarca-montero.etal01.pdf" target="blank" rel="nofollow">1</a> These Th2 to Th1 shifting immunomodulator drugs and supplements include: inosine pranoxbex(Imunovir) and oxymatrine.<a href="http://www.ncbi.nlm.nih.gov/pubmed/26011933" target="blank" rel="nofollow">1</a> <a href="http://forums.phoenixrising.me/index.php?threads/what-are-the-commonly-available-immune-modulators.33847/page-3#post-525111" target="blank" rel="nofollow">2</a>

Note that Th2 to Th1 shifting immunomodulators can make you feel worse for the first few months, but benefits accrue after that initial period. Dr Paul Cheney believes that the immunomodulator Imunovir will lose it's effect if you do not "pulse" it. Pulsing means taking regular breaks Imunovir, using an on/off regimen such as taking Imunovir for 5 days, then stopping for 2 days. Oxymatrine however should not be pulsed. Note that several ME/CFS doctors say that the supplement inosine is just as effective as Imunovir, but much cheaper (Imunovir is based on inosine).

Azithromycin is an antibiotic that acts as an immunomodulator and can lessen ME/CFS symptoms.<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1562448/" target="blank" rel="nofollow">1</a>

Low-intensity exercises like walking, tai chi and yoga help shift towards the desirable Th1 mode, whereas higher intensity exercise and longer workout durations shift towards the undesirable Th2 mode.<a href="http://www.biomedsearch.com/article/Exercise-medicine-using-exercise-to/202661767.html" target="blank" rel="nofollow">1</a>

Rintatolimod (Ampligen) is an immunomodulator drug that anecdotally has produced near full remission in a very small subset of ME/CFS patients, though for most patients, this drug only appears to yield minor improvements. The drug has been shown efficacious in phase III clinical trials.<a href="http://www.ncbi.nlm.nih.gov/pubmed/27045557" target="blank" rel="nofollow">1</a> Ampligen is administered by intravenous infusion twice a week. Ampligen is expensive, costing around $15,000 a year (excluding the medical costs of the infusions). More info: <a href="http://me-pedia.org/wiki/Ampligen" target="blank" rel="nofollow">Ampligen - MEpedia</a>.

Intravenous immunoglobulin (IVIG) has had mixed results, but can bring benefits (cost is around $25,000 for a course of treatment). More info: <a href="http://me-pedia.org/wiki/Intravenous_immunoglobulin" target="blank" rel="nofollow">IVIG - MEpedia</a>, <a href="http://www.healthrising.org/treating-chronic-fatigue-syndrome-mecfs/drugs-for-chronic-fatigue-syndrome-mecfs-treatment/ivig-intravenous-gamma-globulin-therapy-for-chronic-fatigue-syndrome-mecfs-and-fibromyalgia/" target="blank" rel="nofollow">IVIG and ME/CFS</a>.

Rituximab (Rituxan) is an anti-autoimmunity drug which depletes B-cells in the blood, thereby reducing the autoantibodies made by B-cells which attack the body. A phase II clinical trial of rituximab for ME/CFS showed that around two-thirds of patients derived benefit, sometimes very major benefits.<a href="http://www.ncbi.nlm.nih.gov/pubmed/22039471" target="blank" rel="nofollow">1</a> A phase III clinical trial is now underway. The fact that rituximab clearly works suggest that ME/CFS may be an autoimmune disease (at least in part, or at least in a subset of patients). Rituximab is expensive, costing around $15,000 to $50,000 a year. More info: <a href="http://me-pedia.org/wiki/Rituximab" target="blank" rel="nofollow">Rituximab - MEpedia</a>. Rituximab treatment for ME/CFS patients is available at: the <a href="http://www.openmedicineinstitute.org" target="blank" rel="nofollow">Open Medicine Institute</a>, California ($50,000); and <a href="https://translate.google.com/translate?langpair=no%7Cen&u=http://kolibrimedical.no/" target="blank">Kolibri Medical</a>, Stavanger, Norway ($15,000). <a href="http://translate.google.com/translate?langpair=no%7Cen&u=http://www.dagensmedisin.no/artikler/2015/11/23/tilbyr-privat-me-behandling-med-kreftmedisin--forskere-reagerer/" target="blank">More info</a> about Kolibri. Kolibri find that rituximab treatment cures ⅓ of ME/CFS patients, makes an improvement in another ⅓ of patients, and has no effect in the final ⅓ of patients.<a href="http://forums.phoenixrising.me/index.php?threads/rituximab-im-from-holland.47807/#post-784919" target="_blank" rel="nofollow">1</a>

From: 'gcmaf and maf 878' <a href="http://www.enlander.com/services/gcmaf-maf-878/">http://www.enlander.com/services/gcmaf-maf-878/</a>

Another set of Immune system modulators are Macrocyte Activating Factors, GcMaf and its related compound MAF314. GcMaf was discovered by Yamamoto in the 1990’s and the substance was not researched until recently when Kenny de Meirleir and Paul Cheney looked at its use in ME/CFS. We also will examine the action in ME/CFS.

GcMAF (macrophage activation factor) is an immune-regulating compound discovered in the US but now only obtainable from Europe . It os suggested that is is an adjunct to a dysfunctional immune system. . It has been used experimentally in HIV and cancer for several years. It is believed that that as an immune system regulator, that GcMAF may reverse the course of a number of diseases. There are publications demonstrating the efficacy of GcMAF, but further research is needed, as some claims may not have been rigorously tested.

Nagalase is an enzyme that prevents Vitamin D receptors (VDR) from being activated on the surface of the macrophage. As a result, macrophages are not “activated” and our immune systems are not able to properly respond to invaders. There is a blood test for Nagalase levels that has been suggested to determine whether or not one might be a candidate for GcMAF therapy. However, he nagalase test that is presently available is not subject to quality control acceptable to our requirements.

Here are some claims made by the manufacturers of GcMAF:

GcMAF has reportedly been tested more for safety, purity, etc. than other human blood products.

Macrophages are cultured, destroyed, and the GcMAF receptors are purified.

The primary test used in looking at whether or not GcMAF may be a reasonable intervention is nagalase if we can find a suitable lab that runs adequate quality control.

In healthy college students, a nagalase 0.4 is not uncommon (the lower the better).

Nagalase inactivates macrophages.

By using GcMAF to activate macrophages, nagalase drops, and one may regain a functional immune system. The door is

then closed to further invaders and we may no longer serve as a microbe hotel.

Treatment is via injection 1x/week for 8-20 weeks. Dose is titrated initially to avoid exacerbation IRIS a type of Herx response.

Maintenance therapy should not be needed once the immune system is once again properly functioning.

Activated macrophages only remain active for 7 days so any negative responses are generally short-lived. That said, some people do have strong inflammatory responses that are not believed to be typical die-off reactions.

It has been indicated that other medications may be needed in our clinic we use our standard Hepapressin or Nexavir protocol.

VDR genetics do not seem to play a role in predicting response as earlier thought according to one practitioner that I have spoken with. That said, Vitamin D levels do correlate with the positive response rate of GcMAF. Thus, Vitamin D supplementation may be required in order to optimize outcome.

Other than die-off reactions or activation of symptoms (inflammation), no other side effects are generally expected.

Nagalase should be monitored every 1-2 months while on treatment to determine the required duration of the therapy.

Target nagalase after treatment would be 0.4 to 0.6. Again a suitable lab has yet to be found.

Elevated nagalase has a profound detrimental effect on the immune system. Elevated nagalase is often presumed to be related to microbes of viral origin or cancer. Viruses that are nagalase producers open the door to chronic infections.