Want to listen to the blog? Thanks to Geoff for providing a narration of it. 🙂


The multiple sclerosis drug Copaxone (glatiramer acetate) is back in the chronic fatigue syndrome (ME/CFS) news. Health Rising first reported that Copaxone helped some ME/CFS patients back in 2015, and Jarred Younger included it on his list of possible drugs for ME/CFS and fibromyalgia (FM) anti-neuroinflammation drugs way back in 2014. Ron Davis reported that Copaxone made ME/CFS patients’ cells behave normally during the nanoneedle stress test in 2019.

Microglial Inhibiting Drugs, Supplements and Botanicals to Combat Neuroinflammation

In “Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“, Copaxone has moved out of the purely anecdotal realm. We’re getting some solid data on the Copaxone multiple sclerosis/ ME/CFS connection, courtesy of Ron Davis and Michael Jensen and their colleagues at Stanford, the Open Medicine Foundation, and most importantly, the Vinod Khosla Foundation.

We still don’t know if Copaxone works in ME/CFS, but a pathway has been formed that suggests it might and could lead (one might hope!) to clinical trials at some point.

Demyelination MS

The kind of overt demyelination found in MS is not found in ME/CFS. Lower levels of demyelination are possible, however.

Multiple Sclerosis and Chronic Fatigue Syndrome (ME/CFS)

The MS ME/CFS connection has gotten even more intriguing. Both diseases feature high levels of mysterious fatigue, both can produce remitting/relapsing phases, both mostly affect women, and both are often triggered by an Epstein-Barr virus infection (ME/CFS, often immediately and MS, often decades later.)

They also differ. MS is a severe demyelinating disease where damage to the protective myelin sheath covering the nerves in the brain impedes nervous system signals. Hints that demyelination is taking place in ME/CFS have cropped up from time to time, but nothing like the overt structural changes found in MS are present in ME/CFS. Plus, one study suggested while fatigue is high in MS – perhaps even higher than that found in ME/CFS – post-exertional malaise is rare in MS.

The Fatigue in Multiple Sclerosis, Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia – Is it the Same?

In MS, a protein called MBP, which protects the myelin sheath, leaves the sheath and enters into what constitutes “no man’s land” for it – the bloodstream and cerebral spinal fluid – where it’s now perceived as a threat and sparks an autoimmune response. That autoimmune response then targets the myelin sheath.

Similar to the ways ships protect themselves by firing off “chaff” to attract missiles to them, Copaxone appears to act as a mimic that causes the immune system to attack it rather than the myelin sheaths of the nerves.


  • Health Rising first reported that the multiple sclerosis drug Copaxone helped some ME/CFS patients back in 2015, and Jarred Younger included it on his list of possible drugs for ME/CFS and fibromyalgia (FM) anti-neuroinflammation drugs way back in 2014. It’s only now, though, that we have some solid evidence suggesting it might work.
  • Both ME/CFS and MS feature high levels of mysterious fatigue, both can produce remitting/relapsing phases, both mostly affect women, and both are often triggered by an Epstein-Barr virus infection (ME/CFS, often immediately; and MS, often decades later.)
  • They also differ. None of the overt demyelination found in MS has been found in ME/CFS. Some hints of demyelination have been found in ME/CFS, though, and microstructural damage has been found in the brains of ME/CFS and MS as well as fibromyalgia and long COVID.
  • That’s intriguing as recent studies suggest that the fatigue in MS – which may be even stronger than that found in ME/CFS – is caused by microstructural problems that occur early in the illness. It’s possible, then, that similar microstructural problems could produce fatigue in ME/CFS. (Note that one study did not find evidence of post-exertional malaise in MS).
  • Copaxone draws away the antibodies that attack the myelin sheaths covering the nerves in multiple sclerosis. The fact that several ME/CFS patients reported benefits from Copaxone made it of interest to Ron Davis at Stanford.
  • The Stanford researchers led by Ron Davis and Michael Jensen first assessed whether higher levels of the antibodies that attack the nerves in MS were present in ME/CFS and found that they were in about half the ME/CFS patients.
  • Next, they determined that the antibodies found in ME/CFS were similar to those found in MS, and that Copaxone was able to inhibit them in ME/CFS in the lab.
  • They proposed that these antibodies and others known to attack proteins be further assessed in ME/CFS. Plus, Davis proposed that given the similarities between the ME/CFS and MS, other MS drugs should be trialed in ME/CFS.
  • He proposed that similar pathways may be at work in ME/CFS and MS. Indeed, several MS fatigue studies directly referred to findings in ME/CFS to help explain the fatigue in MS.
  • The study was limited by its small size and the emphasis on laboratory work. It suggests that Copaxone is doing the same thing in ME/CFS as it does in MS, but we won’t know that absent a clinical trial. Time will tell if this study leads to a Copaxone clinical trial in ME/CFS, but it does appear to set the stage for one.
  • In the meantime, Ron Davis and Janet Dafoe would love to hear the experiences of anyone with ME/CFS who has tried Copaxone. You can email the Open Medicine Foundation or Janet at janet.dafoe@gmail.com

The Study 

With some ME/CFS patients providing anecdotal evidence that Copaxone – which targets the autoimmune processes in MS – may be helpful, the search was on to see if the abzymes (antibody + enzyme) (ABS) that Copaxone targets were present in ME/CFS.

If I have it correctly, the Stanford researchers assessed the ability of the antibodies to MBP (called ABS) in the plasma of 19 ME/CFS and 19 HC patients to digest (destroy) MBP. They found that about half the ME/CFS patients’ samples damaged large amounts of MBP, while only 5% of the healthy controls did.

Next, they took the antibodies from the ME/CFS patients’ plasma, determined if they could attack the myelin sheath, and found they could. That suggested that demyelination – a breakdown of the protective sheath covering the nerves – could be happening in ME/CFS as well.

Then, they determined whether Copaxone was able to prevent MBP from being attacked and degraded in the ME/CFS patients’ plasma – and to a significant extent (68-80%), it was. That made it clear that the same ABS antibodies are found in both MS and ME/CFS, and that the drug operated normally in ME/CFS patients.

Finding the same antibodies in ME/CFS, demonstrating that they had the potential to do the same thing in ME/CFS, and that Copaxone could stop that process in the lab, seemed to potentially set the stage for a Copaxone trial in ME/CFS.

Next Steps

The authors argued that given the broad spectrum of overlapping pathologies found in MS, other autoimmune diseases and ME/CFS and long COVID, that demyelination, particularly in ME/CFS patients experiencing nerve pain and muscle weakness, should be considered.

They recommended that studies to track the “catalytic activity” (i.e., the ability of the ABS (the antibodyzymes in question) to break down myelin in ME/CFS) should be assessed over time. Levels of ABS in the cerebral spinal fluid – typically a richer source of these antibodies – should be assessed as well, and so should other “proteolytic” antibodies – antibodies that break down proteins.

They closed the paper by stating that an assay that tracks MBP breakdown by these ABS in ME/CFS patients may help “better diagnose and treat patients in the early stages of demyelination”. From what I gathered, that test is only available in a research setting, however.

During a talk, Ron said that one next step was determining if MS treatments – not just Copaxone but other MS drugs as well – are helpful in ME/CFS.

He noted that the study suggests that some people could have an autoimmune disease like MS in addition to ME/CFS that might be treatable. Then Ron said something interesting – he thought that because ME/CFS affects major control circuits that play a role in other diseases, treatments that help other diseases might work in ME/CFS.

This makes perfect sense. While Ron noted that ME/CFS is extremely complicated, it’s not as isolated as we might think. The basal ganglia alterations in ME/CFS look like those found in hepatitis C IFN-treated patients and MS. The autonomic nervous system issues (high fight/flight) are present in many other chronic illnesses. A similar kind of exercise intolerance may be found in rheumatoid arthritis. Jarred Younger is certain that neuroinflammation is present in ME/CFS, and neuroinflammation pervades neurological diseases.

The reason really effective treatments are hard to come by in ME/CFS may have more to do with funding than because ME/CFS is some sort of untreatable, undecipherable disease. MS is no walk in the park, but it gets ample funding, and the FDA has approved over 25 drugs to treat it. Because bits and pieces of ME/CFS are found in many other diseases, drugs that affect those aspects of ME/CFS could very well help.

The study had significant limitations. It was small and because much of it was done in the lab in test tubes, we don’t know that this antibody-triggered demyelination is actually occurring in ME/CFS. It presents a nice starting point, though, and we will see how it evolves.

The Microstructural Fatigue Diseases?

The fatigue in MS is curious. It usually shows up before neurological symptoms do, is often described as the worst symptom MS patients experience, and, most intriguing of all, does not track with the degree of overt demyelination or nerve damage found. A recent study suggests that it may, however, track with microstructural changes – and here we have another potential opening for ME/CFS.

Using advanced MRI techniques, the 2024 MS study found that small microstructural changes that occurred very early in the disease process were associated with cognitive fatigue. The study reported:

“brain microstructure within normal appearing tissues is already altered in the very early stages of the disease. Moreover, additional microstructure alterations (e.g. diffuse and widespread demyelination or axonal degeneration) in pwMS may lead to disease-specific complaint of cognitive fatigue.”

Could similar microstructural changes be causing similar symptoms in ME/CFS? Microstructural changes to the brainstem, the insula, and a major communication track (superior longitudinal fasciculus) have been found in ME/CFS. Microstructural damage has also been found in fibromyalgia and several times in long COVID as well.

In fact, one long-COVID microstructural study, “Brain microstructural changes and fatigue after COVID-19”, went straight to the ME/CFS literature to explain what they’d found. They focused on the impaired “remyelination”, abnormal connectivity, reduced conduction in the brainstems, insufficient myelination of motor cortex tracts, and the basal ganglia findings in ME/CFS to explain the fatigue in both diseases.

More possible connections showed up in an MS fatigue study which proposed that the basal ganglia – a prime candidate in ME/CFS and FM – was “the fatigue center” in MS. That study also cited ME/CFS findings to support their hypothesis.

A Fatigue Nucleus in Multiple Sclerosis… and ME/CFS and Fibromyalgia?

Plus, each of the four hypotheses regarding fatigue in MS from a 2015 review article has been raised for ME/CFS as well. They included:

  • Compensation – The loss of signal strength between brain regions causes other parts of the brain to jump in to compensate, reducing efficiency and increasing metabolic needs – producing early fatigue.
  • Brain stem damage impairs the activation of the cerebral cortex which is connected to two brain organs – the thalamus and basal ganglia involved in alertness, the autonomic nervous system and movement.
  • Motor region – Lesions in the motor cortex region are associated with quick fatigability in MS during physical exercises.
  • HPA Axis – Lesions in the hypothalamus in MS patients affect circadian and endocrine factors. The disruption of the circadian rhythm can impact sleep – causing fatigue, and endocrine factors regulate metabolic and immune processes.

The physical problems caused by nerve damage found in MS do not occur in ME/CFS, but it’s possible that the fatigue found in both diseases could be similar. If so, a drug like Copaxone that helps with fatigue in MS might help with the fatigue in ME/CFS.

One way problems with the microstructure of the brain could affect ME/CFS patients is by impairing the connectivity between different brain regions.

Bad Connections

Frayed wires

Frayed wires caused by demyelination could be contributing to the connectivity findings in ME/CFS.

Demyelination could also contribute to the “connectivity” problems frequently found in ME/CFS. Connectivity problems occur when parts of the brain aren’t communicating properly with each other.

For instance, in 2018, Staud found during a cognitive exercise test that the connections between the brain regions associated with working memory, sensory function, and motor function (there’s the motor cortex again) broke down in people with ME/CFS. Numerous brain regions demonstrated opposite patterns of connectivity in the ME/CFS patients relative to those found in the healthy controls.

  • healthy controls showed increased functional connectivity to the right-lateralized middle temporal gyrus, superior lateral occipital cortex, and angular gyrus; ME/CFS patients showed decreased connectivity
  • healthy controls showed increased coherence (communication) between the right-lateralized middle temporal gyrus, superior lateral occipital cortex, and angular gyrus; ME/CFS patients showed decreased coherence
  • healthy controls showed increased connectivity between the hippocampus and right superior parietal lobule; ME/CFS patients showed decreased connectivity
  • healthy controls showed increased connectivity to the left-lateralized pallidum, thalamus, putamen, caudate, and nucleus accumbens; ME/CFS patients showed decreased connectivity.

The authors proposed that the generally increased connectivity/coherence seen in the healthy controls reflected their brains’ ability to bring in new brain regions to help out as the fatiguing task wore on. The inability of ME/CFS patients’ brains to tap more resources, in turn produced their fatigue.

Back to Copaxone

Copaxone is one of the few drugs able to treat fatigue in MS, and anecdotal reports suggest it may be able to do the same in ME/CFS. Plus, as noted earlier, Copaxone was able to restore ME/CFS patients’ cells to normal functioning when they are put under stress using the nanoneedle.

Diffusion tensor scan

As brain imaging technology improves, we will learn much more about what’s happening in the brains of ME/CFS patients. This is from a diffusion tensor scan which can pick up microstructural changes.

As the technology to assess the microstructural integrity of the brain improves, and as it’s brought to bear on ME/CFS, FM, and long COVID, it’s going to be fascinating to see what it shows. To reiterate, none of these diseases demonstrate the kind of overt damage to the myelin sheaths found in MS – and that’s a good thing. Repairing that kind of damage may be impossible, but repairing damage to the microstructure might be another story. When asked if Copaxone could repair the damage, Davis said he didn’t know – and the best thing would be to try to avoid that.

When asked if these results would show up on a standard MRI, Davis said he wasn’t sure, but they thought that the various spots on an ME/CFS patients MRIs indicate demyelination. I looked it up, and they do. Increased white matter hyperintensities have been found at times in ME/CFS and could indicate that myelin degradation may have occurred.

Ron noted that it’s possible that the amount of antibody in ME/CFS is not as high as in MS, and therefore, not as much damage is occurring. He also poo-pooed the idea that one couldn’t have MS and ME/CFS at the same time. He also noted that the MBP antibody is not a diagnostic test for MS.

They would love to hear the experiences of anyone who has tried this approach. You can email the Open Medicine Foundation or Janet at janet.dafoe@gmail.com

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