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.”

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.

  • poetinsf

    Having no other drug in the pipeline is no reason to approve. Ampligen has been a drug in search of disease to treat, and it’s efficacy for CFS has been rejected by FDA before. I’m sure they’ll keep trying till they find the result they like, or find regulators who will accept what they have.

    CFS symptoms may be nonspecific and vague, but that doesn’t mean they can’t be measured. Subjective fatigue measures can be fairly accurate and measurement by things like SF-36 are totally valid. As long as the trial is randomized and blinded, that is.

  • Karl Gallagher

    A disease that may not exist and a drug looking for a disease. Hmmm…

    • Brian Thompson

      With all due respect, the disease most certainly exists. My life has been completely ravaged by it. So to be in need of a cure so desperately, and then to hear people who are not educated about the science and facts of the disease go on public forums and spread ideas that the disease “may not exist” is extremely disheartening for someone whose life has been taken away by this disease and who is praying for a cure every day. I am not angry at all, nor am I attempting to start an argument, and I am sure your comment was made with the most innocent of intentions, but I just felt like I should let you know this disease is as real as it gets, and a cure is urgently needed. If you care to read about my specific case, you can do so here: https://cfsthelongpause.wordpress.com/2015/12/09/brians-story/

      • Brian Thompson

        Actually, if you want an example of what CFS can really do to a life and a family, read the brief story of this Stanford scientist and his son. https://www.washingtonpost.com/national/health-science/with-his-son-terribly-ill-a-top-scientist-takes-on-chronic-fatigue-syndrome/2015/10/05/c5d6189c-4041-11e5-8d45-d815146f81fa_story.html

      • Sharon Campbell

        Sorry, Brian, zero respect is due to Karl. A tiny bit of research would have shown him how wrong he is.

      • Sharon Campbell

        My husband has been sick since 1993. When he was diagnosed, the doctor said “The good news is that it is not terminal. The bad news is that it is not terminal.”

        • Brian Thompson

          Exactly. In severe cases, it is almost like you die without dying. For people with moderate to severe CFS, they may not be dead, but they are certainly not living. Not to sound disrespectful toward another serious illness, but I would trade my CFS for cancer or HIV in a heartbeat, and do it with tears of joy streaming down my face. Simply because HIV nowadays is manageable, and you can live a near normal life and have a normal life expectancy. And cancer is usually treatable now, and at least if you have cancer you know that you are either going to live or die, and if you die you won’t have to experience it. CFS can be like dying but not losing consciousness. It is like die but you don’t really get to die. Fortunately for me, I am still able to function at least a little bit, and I am not totally bedbound. I just feel for those people who are. That is a true living hell. Okay okay enough rambling from me, I just can get a little carried away talking about it, because it is so real to me, as I know it is to you also!

          • Emiya

            Brian – i can relate on the declined activity, CFS is awful no matter what degree you have of it. I am lucky that i can still work but my doc doesn’t think i should be. People need to understand how debilitating it is, and i wish that more doctors were aware of it.

  • Spencer James Smith

    no, it won’t. this won’t lead anywhere whatsoever but masking symptoms and maybe creating more problems. thats what big pharma does largely.

    • Texshan

      Oh, jeez, another “big pharma is out to kill us all” idiot …

      • Teresa Blommers

        did you know Tamoxifen is a carcinogenic?

        • agscienceliterate

          On Tamoxifen and other probable or possible carcinogens, please read, from the American Cancer Society:

          http://www.cancer.org/cancer/cancercauses/othercarcinogens/generalinformationaboutcarcinogens/known-and-probable-human-carcinogens

          • Spencer James Smith

            please read from those who profit from “treating cancer” with extremely expensive poison.org

          • Spencer James Smith

            lol. The american cancer society that was started by the Rockefellers. After Trillions of dollars of research for the last 100 years of cancer research what have they come up with? Surgery, poison and radiation (two of which cause cancer in many cases). Perfect example of Orwellian double-think deception. It’s ridiculous.

    • Robert Baden

      Outside of bacterial infections I think there have been very few cures. And even in those cases you rely on the body to heal any damage.
      Most advances have been in prevention. There never was a “cure” for polio, just a vaccine that keeps you from getting it.

      • Spencer James Smith

        that vaccine doesnt work.

        • agscienceliterate

          You are saying the polio vaccine doesn’t work? Any citations for that ridiculous assertion?
          Tell that to millions of children who statistically otherwise might have gotten polio.
          Ah, yes … just checked your other posts. You are a rabid anti-vaxxer. And you even posted elsewhere that Zika doesn’t cause microcephaly. What a deep thinker.

          • Spencer James Smith

            i will. yes i have citations. but are there peer reviewed studies that show the polio vaccine doesnt work? i dont think there are. good thing i am an independent critical thinker and can piece together conspiracy and corruption with massive amounts of evidence. i am thankful that i dont have to rely on the claim of a “peer reviewed” fact to tell me what is true and what isnt. ever consider that the method could have been biased or corrupted and what they say has been peer reviewed and therefore scientific evidence is actually a lie?

            open your fricken mind and stop being a slave.

          • agscienceliterate

            Please post, then, your credible citations that the polio vaccine “doesn’t work.”

            As you are a rabid anti-vaxxer, I am sure you have this info at your fingertips. Let’s see it.

          • Spencer James Smith
          • Spencer James Smith
          • Spencer James Smith
          • Spencer James Smith

            first you need to understand how this system can be corrupted. even mainstream sources talk about tobacco science. they try to let you think that its a thing of the past and a lot of money is put into making people think it isnt happening with other products.

            you dont even have to believe the healthcare system and big pharma is in collusion with the government. you first just have to accept that its possible and i pretty much know how it works. if you cant accept that, then our conversation wont go anywhere. you dont seem like you want to learn anything and i feel quite certain i will not learn anything from you in anything that relates to this subject. so the choice is yours.

          • Spencer James Smith

            hahah. deep thinking gets answers. you are a spineless slave to trusting whatever the mainstream media or officials say is a fact. as long as they say its peer reviewed or that its been studied, then its just true isnt it. nope, no such thing as biases, corporate science, computer generated studies, fake peer review information or bought of “peer” reviews. thats impossible. what stupid conspiracy tinfoil hatted freak would ever think that this system could be corrupted? imagine if there was a time when tobacco companies bought science and infiltrated the FDA to get people to think that smoking was safe and didnt cause lung cancer. HA, can you imagine??

        • Lisa

          you’re a real brainiac hey Spencer? Troll much.

          • Spencer James Smith

            I am a citizen concerned for humanity. I try to spread what I believe is the truth. I do a lot of research, prayer and reflection. I have invested literally thousands to research corruption in the pharmaceutical industry.

        • PhDMIT

          Care to explain why there have been virtually no cases of Polio in vaccinated populations? How many people with Polio do you know? BUT HEY – don’t believe your own eyes – believe some charlatans. As P.T. Barnum said, there’s one born every minute.

    • Lisa

      not helpful sir.

  • The_Old_Geezer

    CFS can be from many things, including a bacterial or several bacterial infections that basically has one’s body in a 24/7 war that it is not winning. Clue: Define the specific bacteria(s) involved and deal with them one at a time. There is no magic bullet that is going to deal with the possible multiple root causes of CFS.

  • david hockney

    “This is considered validation of claims by CFS sufferers that the condition is physical illness rather than a psychological one.” What is? The fact that a drug appears to help? Drugs have been known to help psychological conditions too. So do sugar pills. The drug is not new either. It has been around since the 70s. The trials were inconclusive. And still are not up to FDA approval. Not mentioned is the fact that it costs around $20000 a year and must be taken continuously. Ben Locwin obviously has more than an academic interest here, as he works for several companies developing microbial pharmaceuticals. So, up your usual standard of scientific rigor then. Junk science.

    • Lisa

      You need to read about this drug. Ampligen is a heavy hitting cancer drug that’s been around a long time. It was accidentally found to work on a sub set of CFS patients in the States and Canada. The studies are fascinating and there are a lot of peer reviewed papers regarding the research.
      It is a VERY expensive IV drug. i think about 20,000 U.S. a year is the # i recall.(u;d have to check to be sure). It’s not a cure. It’s a treatment and when the drug has been stopped, people do relapse. No one said it’s a perfect science. Not something to be played with either but if you’re as sick as some of us for as long as some of us, you’d jump at the chance if allowed.

  • deboruth

    “…low probabilities…” !!! Is it possible Ben Locwin acquired his degrees without first learning how to count? More than one million people have this disease in the United States alone. That is close to HIV-AIDS 1.1 million (US) and more than twice the count for Multiple Sclerosis. In fact, it approximately equals the “0.33% Locwin cites. Equally, there are plenty of measurable symptoms. But only for people who can count.

    • Devon McUK

      I don’t think insults will get you the response you want. Mr. Locwin has done an admirable job. You’re talking about two different things (probability compared to a count of people). There are a lot of people as an absolute number, because there is an incredibly huge population in the U.S. But in terms of relative proportion, it is very small. Not to mention that any estimates of CF occurrence are just ‘estimates’ because there are no real tests or symptoms that can definitively determine it.

      • deboruth

        A. I don’t want a response. Why would I? B. One million or .33% is a lot for a disease irrespective of whether you are talking of probability or absolute numbers, and even in the US. Mr. Locwin cites it as a reason for difficulty in assessing either the nature of CFS or the efficacy of Ampligen — the context suggests either or both, yet neither seems justified. Nor does his claim that it is difficult to assess improvement in the disease appear justified. Any activity measuring device — cheaper and simpler versions of the FItBit for example — will allow one to assess improvement for starters. One would also access other measures of gain in function, such as improvement in cognitive processing times. There is no measure necessary that is not already measured readily in medical research.
        Further on the subject of numbers: yes, a vast disease such as diabetes comprises more than 29 million persons already diagnosed — 9.3% of the population. But HIV-AIDs is a big, well-known disease despite similar (to CFS) numbers and probabilities. MS and Rheumatoid Arthritis are big and well-known with smaller numbers. A mere 263 is considered an extremely big number in terms of measles — it is the number of Americans who died from measles the final year before measles vaccinations began.
        My point is that an allegedly “small” probability Is NOT the reason so-called “ME/cfs” is little understood, little researched, and barely treated.
        While I am entirely sympathetic when some exhausted young reporter who has to post to social media umpteen times a week and plunge on a moment’s notice into new subjects every other day skims the facts on “cfs” I am less sympathetic with someone “eminent” who prognosticates as an “authority” yet cannot be bothered to notice the fact that the disease in question has history that includes various viral and a few bacterial and other agents going back to the rise of polio in the late 19th century. Said illness (minus CDC amplification) has been listed under “neurological diseases” in the WHO ICD since 1969. Such eminences can take the time or order their underlings to get straight the fact that the CDC announced its invention of CFS in 1988, after it first observed an outbreak of M.E. that began in 1984-85 or so in Nevada. CDC then undertook to strip that outbreak of key observed symptoms (in publications) and name the consequent invention — by then as now an umbrella for M.E. plus a miscellany of mis-diagneses — with the demeaning and misleading name of chronic fatigue syndrome.
        Ampligen, by the way, appears to have brought back to life a bit above 50% of the few people in the US out of the many severely handicapped by ME/”cfs”privileged to be included in self-paid “trials.” Its chief problem has been that the previous CEO refused to hire an FDA vet to keep his studies on the rails, and now there is no money for more. Earlier trials proved the drug safe, though efficacy numbers seemed small to people not familiar with the extreme energy thief that is CFS. It is also demanding to handle and administer via infusion. But the worst obstacle vis-à-vis FDA is that, unlike HIV-AIDS patients, ME/”cfs” patients are majority female and too geographically dispersed to count politically. If Ampligen were to greatly lessen morbidity in more than 50% of HIV-AIDS patients, as it does ME patients, the FDA would have it selling like hotcakes.

        • Devon McUK

          If CFS is as well-understood and has so many ‘facts’ about it already, then why do most clinics, physicians, and emergent care settings not even consider it a ‘real’ disorder? It falls into the category usually of chronic Lyme, fibromylagia, etc. which have a big ‘mental’ component.
          M.E. is what people prefer to have it called so that it legitimizes their complaints.
          There’s more on this naming controversy here (unless these experts are also not working hard enough to fabricate a disorder):
          http://www.theatlantic.com/health/archive/2015/10/chronic-fatigue-patients-push-for-an-elusive-cure/409534/
          …And no – a ‘cheap’ version of a FitBit will not allow people to show progress. They are not validated for this, and if someone took 2,100 ‘steps’ last week, and 2,405 ‘steps’ this week, that does not indicate improvement. It could just be measuring variance of the cheap device. Or uphill walking last week versus downhill walking this week. This is why psychological tests and motor function testing go through endless batteries of validation – so they’re not measuring nothing.
          And by the way, CFS IS ‘little understood’: No one even has a demonstrable causal agent for it. All this talk about ‘it’s bacterial…’ or ‘it’s viral…’ has led to no reproducible evidence that there is a particular cause. And saying that ‘this, this, this, and this’ are potential causes means there’s no answer.
          And as to your “point is that an allegedly “small” probability Is NOT the reason so-called “ME/cfs” is little understood, little researched, and barely treated”: it could be because CFS hasn’t ever been demonstrated to be ‘real,’ isn’t communicable, and isn’t fatal like some of the other diseases you mentioned. Because of their relative status, they get funding – and CFS doesn’t.

  • Emiya

    Are there any studies/trials for this drug? I’m planning on talking to my doctor about it. I have CFS, undiagnosed but know that i have it in addition to fibro. Currently i am hopeful for medical marijuana but it won’t be ready in my state until 2018. I’m ALWAYS tired, sleep is unrestful and often painful. I have tried multiple sleep medications prescribed by a doctor, most recent was Amitriptyline and that crap didn’t work. Problem is i have reacted poorly to a lot of medications. I am still trying to stay active and work, but its exceedingly difficult. Driving is especially hard and i can’t go as far now. Last summer i was nearly bed-ridden for most of it.

  • Angelica Kaufman

    I found my answer and it turned out it was simple. I take CoQ10 enzyme. if I go off of it for even a week the chronic fatigue comes back and I’m falling asleep where I sit again

    • Angelica Kaufman

      they always said it’s just something that comes with my multiple Sclerosis at the neurologist. My PCP suggested this and it saved me

    • Lisa

      there are many cases where chronic fatigue is the SYMPTOM not the DISEASE known as Chronic Fatigue Syndrome. They’re different animals. So glad you found something that works for you to help your fatigue. I haven’t been so lucky.

      • Angelica Kaufman

        Mine is ms related they say

  • CJ

    It most certainly exists. I was the healthiest person until coming down with an extreme case of mono at 19. My blood work was such a mess, that my family Dr. sent me to a hematologist. (Liver enzymes super high, WBC off & enlarged spleen). It took me almost 6 mos to recover & I have never been the same since. I get sick constantly with upper respiratory infections & have extreme fatigue. I try my best to not let it run my life & try to run or get an hour of cardio in 4-5 days a week but on some days, I can barely keep my eyes open. I chug coffee just to get through the day, but it is a constant struggle. Family & friends don’t understand why I sometimes need to cancel plans last minute & this disease has drastically affected my quality of life. It is so sad because your brain wants to do things & your body just doesn’t have the energy. I would do anything to get my pre-mono life back. It IS very real.

  • Lavina of Rome

    Great article!!! I have CFS but I prefer the new name SEID and think that the supplement industries profiting off this condition is very harmful. I’m against the name ME for it because it makes it sound like a cause has been found but “the system” has been trying to suppress it for decades which is conspiracy theory nonsense, we are not even close to really pinning down which areas are defective in SEID.

    This is the first time I have found a good, pro-science skeptic article that does not mostly or entirely dismiss the idea that SEID could be a physical illness out of hand. I had NO IDEA that SEID is rare! A lot of advocacy orgs for it try to make it seem common but I have been skeptical of that because as you mentioned, most criteria and screening for it are waaaay too liberal.