Founder of Health Rising and Phoenix Rising
Immune Modulators To the Fore in Chronic Fatigue Syndrome
"The results of this study may expand treatment options for patients with CFS, for whom graded exercise therapy and cognitive behavioral therapy are the only evidence-based interventions that exist at this moment."
The Rituximab trials, Ampligen studies, the etanercept work by Fluge and Mella, and statements by Dr. Klimas indicate that researchers are becoming more comfortable with the idea of using powerful immune modulators to treat chronic fatigue syndrome.
Within the past year an ME/CFS immune modulator clinical trial has begun in a country - the Netherlands - best known for its CBT studies. If the trial is successful it will open up new treatment possibilities for ME/CFS.
It's also an example of changes that appear to be slowly occurring. Somebody, after all, got enough money together to do what an appears to be a quite expensive trial on an immune modulator in the Netherlands. That's something to think about.
Anakinra is an IL-1 receptor antagonist; i.e. it stops IL-1 -a key pro-inflammatory cytokine that broadly regulates the immune response during infection - from working. Different types of IL-1 prompt the hypothalamus to produce fever, rush immune cells to the site of infection, lower blood pressure and increase pain sensitivity.
Eleven members of the ILI-1 family are produced mostly by immune cells associated with the innate or early immune response such as macrophages, monocytes, fibroblasts, and dendritic cells. When cells are stressed by low oxygen levels, oxidative stress, infection, high acid levels, etc. they also put out precursors to IL-1a called alarmins that alert the immune system to the possibility that danger may be present.
IL-1 also plays a major role in neuroinfllammation. A recent review concluded that neuroinflammation (microglial activation) in animal studies is associated with increased IL-1b, TNF-a and several toll-like receptors.
IL-1 antagonists are used to treat rheumatoid arthritis and other autoinflammatory syndromes as well as gout, epilepsy and inflammatory lung diseases. According to Wikipedia, blocking IL-1 production is now considered standard therapy in the treatment of autoimmune disorders and cancer.
Cytokine Blockers in Chronic Fatigue Syndrome?
Cytokine blockers have been mostly blocked from being used in ME/CFS in part because cytokine results in ME/CFS tend to be very variable. Neither IL-1 nor any other cytokine has being definitively associated with it.
Some successes have occurred. The Lipkin/Hornig cytokine study showed cytokine elevations early in the disease, and Taylor was able to produce an algorithm involving Il-6, IL-8, IL-23 and I-1a and other cytokines that correctly identified 80% of post-infectious mononucleosis patients with chronic fatigue.
Broderick's and Younger's work, however, suggests that cytokine levels may not need to be high to have significant effects. The altered immune networks Broderick has found in chronic fatigue syndrome indicate that given the right context, small cytokine elevations can have major impacts on the rest of the immune system.
Anakinra, they noted, is a good cytokine inhibitor to try out in ME/CFS because it does not cause severe side effects.
Given their reasoning it's possible that emerging evidence of neuroinflammation in ME/CFS helped get this study underway. It also suggests that more definitive evidence of neuroinflammation in ME/CFS and FM - if it occurs- should greatly open the possibilities for treatments and more clinical trials.
This randomized, placebo-controlled trial will measure symptom levels, functionality, pain levels, psychological distress, cytokine levels, cortisol and and even the microbiome (gut flora).
It's not clear who is funding what appears to be a rather expensive study. (The responsible party is listed as Radboud University).
The study has already begun and is expected to last through June, 2016. The contact person for the study is Megan Roerink, MD at Megan.Roerink@radboudumc.nl'
Attitudes Slowly Shifting
Despite its history of immune research, the U.S. continues to be the odd man out. The NIH is a major funder of drug trials yet Ampligen was treated harshly by the FDA panel and has, despite its promise and the needs of the ME/CFS community, received no federal help. Rituximab has had solid results in small trials as well, but as yet no help from the federal government in producing a U.S. clinical trial has occurred.
When the biggest medical research agency in the world will step up and help out is a very good question. For now, it's good to see other countries taking the lead on new treatment possibilities in ME/CFS.