New drug approved for Chronic Fatigue Syndrome, as mystery disease causes come into focus

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On August 23, a new drug, rintatolimod, which has the U.S. trade name Ampligen, became the first drug approved anywhere in the world to treat the mystifying condition known as Chronic Fatigue Syndrome. It was approved for use in Argentina but has not yet been approved in the United States. According to the Philadelphia-based company, Hemisphere Biopharma,that developed the drug, “there are no other products in the pipeline for approval, worldwide, for this debilitating disease.”

This is considered validation of claims by CFS sufferers that the condition is physical illness rather than a psychological one.

One of the hardest things to do in science is to pin-down confirmatory results of something not happening—or “proving a negative.” So for example, if you have a rare condition in the general public and you test out a treatment for it and wait to see if the treatment was effective… how long do you wait? How do you know if a period of time with unnaturally-few cases (or no cases) was due to the treatment working, or just that it was very rare in the first place so you’re witnessing small variations of something that almost never happens?

Such is the case with CFS. Not only do fewer than 0.33% of the public report Chronic Fatigue Syndrome, but validating improvement in a patient with CFS is very difficult because we are trying to assess the absence of symptoms, and these symptoms are often vague, non-specific, and very fluid in nature.


So what’s the cause?

In the virology world, we try to identify the ‘causative agent’ responsible for what are oftentimes non-specific or overlapping symptoms. It’s no so different than the case with CFS, which has proven to  likewise be a slippery in pinning down. Some theorized causative agents over the past two to three decades have been Epstein-Barr virus (EBV), Human herpesvirus 6 (HHV-6), Xenotropic murine leukemia virus-related virus (XMRV), and other candidates. None has provided satisfactory evidence for a relationship with CFS.There’s conjecture as well that gut bacteria are related to CFS. There’s even a healthy cottage industry mesmerized with the concept of ‘adrenal fatigue’, which boosts rates of self-diagnosis and confounds the measurement and treatment of real Chronic Fatigue Syndrome.

A new study in published in Microbiome has identified what might be a bacterial biomarker for the disease Researchers recruited 48 people reporting CFS symptoms and 39 healthy controls. They analyzed the bacteria species in their stool and searched for markers of inflammation in their blood.

The stool samples of those with CFS. had significantly lower diversity of species compared with the healthy people, which is also typical of inflammatory bowel disease. The scientists also discovered higher blood levels of lipopolysaccharides, inflammatory molecules that may indicate that bacteria have moved from the gut into the bloodstream, where they can produce various symptoms of disease.


“There’s a biological difference between people with C.F.S. and healthy people,” said the senior author of the study, Cornell University molecular biologist Maureen Hanson. “The long-lasting idea that it’s a psychological illness should be abandoned.”

Related article:  Not so-sterile brains? Researchers find harmless bacteria living there

Recent research published in the Journal of Nuclear Medicine using positron-emission tomography has lent evidence for inflammation in certain brain regions as an associated factor of CFS. Specifically, the researchers found inflammation marker levels (translocator protein, nondisplaceable binding potential (BPND) “in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%–199% higher in CFS/ME patients than in healthy controls.” The inflammation markers positively correlated with cognitive impairment (when found in the amygdala and thalamus), positively correlated with pain (when found in the thalamus and cingulate cortex), and positively correlated with depression (when found in the hippocampus). However with such a small sample size (10 controls, 9 patients) the best that can be claimed for these results is that there may be an association, and it’s a new avenue to research for further exploration to see if continued refined results yield the same conclusions and support the same hypothesis.

As I note previously in a post about the neurobiology and genetics behind addiction, in addition to neurotransmitter receptor density, there is also potentially a link between reduced neurotransmitter quantity and reduced serotonin transporters in those patients suffering with Chronic Fatigue Syndrome. This could indicate an association between genetics, brain structural and functional changes, and CFS.

What we don’t know here still outweighs what we do know. Working against us are the low probabilities of having CFS, and even then–standardizing on a measure of how one knows whether he or she has Chronic Fatigue. The yardstick by which one measures CFS clinical symptomology has very little reliability, meaning that we can’t even know if what we’re looking at is getting better or worse until we know what it is we’re trying to measure.


What is clear is that viruses and our human genes tend to co-mingle and cause structural and functional changes. As we learn more, it proves to be a complicated interrelationship.

Ben Locwin, Ph.D., M.B.A., M.S. is a contributor to the Genetic Literacy Project and is an author of a wide variety of scientific articles in books and magazines. He is an expert contact for the American Association of Pharmaceutical Scientists (AAPS), a member in the American Statistical Association (ASA), and a consultant in the biological sciences, pharmaceutical, psychological industries and for academia. Follow him at @BenLocwin.

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