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Experimental Treatments for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis


By Erica Verrillo*

Technically, all treatments for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis (ME/CFS) are experimental, because there are, as yet, no FDA-approved treatments that are specifically designed to address the underlying disease process. Any treatment or therapy used to lessen symptoms is considered “palliative.” Even treatment protocols that are intended to modulate the immune system, or correct proposed metabolic functions at the cellular or molecular level, such as the methylation protocol, are considered experimental – whether they use drugs approved for other conditions or FDA-approved supplements.

Two highly touted therapies, cognitive behavioral therapy (CBT), and graded exercise therapy (GET), are also experimental, as neither of these has been shown to reverse the illness, and there have been no well-designed double-blind studies comparing these therapies to placebo.

In spite of the lack of FDA-approved treatments, there are two drugs that have been shown to address the immune dysfunction that drives Chronic Fatigue Syndrome & Myalgic Encephalomyelitis. The first, Ampligen, has undergone years of clinical trials. The second, Rituximab, is undergoing privately funded clinical trials in Great Britain. Both treatments are available in the U.S., but, as they are not FDA-approved for ME/CFS, insurance companies do not cover the costs. For most patients, the cost is prohibitive.



Ampligen (poly I:poly C12U) has a long and speckled history with Chronic Fatigue Syndrome & Myalgic Encephalomyelitis. After the Incline Village outbreak in 1984, the FDA invited Hemispherx Biopharma, a pharmaceutical company, to develop a drug to treat the illness. A similar drug, Poly(I)-Poly(C), had been developed in the early 1960s to treat cancer, but it was withdrawn because it was extremely toxic. The toxicity decreased significantly when the structure of the RNA was altered, forming poly I:poly C12U (rintatolimod, trade name: Ampligen).

In 1987 Ampligen was used experimentally in a small group of patients with AIDS (acquired immunodeficiency syndrome). The positive results of this trial seemed to indicate that Ampligen worked by enhancing natural killer cell function and influencing the 2-5A synthetase pathway. This pathway is vital in the defense against viral infections. According to Dr. Robert Suhadolnick of Temple University in Philadelphia, there are defects in key components in the antiviral system in some ME/CFS patients, the most notable of which are low latent 2-5A synthetase and upregulated RNase (ribonuclease) L activity (Journal of Interferon and Cytokine Research, 1997). Ampligen is believed to correct both of these defects.

In August 1988, Dr. Daniel Peterson, who, along with Dr. Paul Cheney, reported the 1984 Incline Village outbreak, used Ampligen on an extremely ill patient with ME/CFS. Because of the severity of the patient’s illness, Dr. Peterson was able to obtain permission from the FDA to use Ampligen under compassionate care status. The results were impressive and encouraging. One year into therapy the patient had recovered near-normal function in some areas and demonstrated a 46-point increase in IQ. This justified the next pilot study by Dr. Peterson, as well as several other formal studies conducted independently.

At the 1990 CFIDS Conference in Charlotte, North Carolina, and at the Cambridge Symposium, Dr. Peterson reported positive results after treating 15 patients with Ampligen. At the end of 24 weeks, most of the patients demonstrated increased performance status (using Karnofsky scores) and exercise tolerance (as measured by treadmill testing). Cognitive improvement was demonstrated by improved memory and increased IQ scores. No significant toxicity was reported. Ampligen’s antiviral properties were confirmed by evidence that human herpesvirus 6 (HHV-6) reactivation was absent after treatment and abnormal components of the 2-5A pathway returned to normal range

The results of Dr. Peterson’s study paved the way for larger FDA-approved double-blind studies, involving 92 patients in four U.S. cities. Again the results were encouraging. Many of the participants had been severely disabled before treatment and required assistance for simple daily activities. More than half of those in the study who received Ampligen demonstrated improvement and many were able to carry out daily activities with minimal assistance.

Dr. Kenny De Meirleir claims that close to 80% of his patients reported “complete clinical recovery” after taking an extended course of treatment. Patients report improvement in overall function, energy levels, cognitive performance, and some have been able to return to work. Dr. Lapp, who has been using Ampligen since 1998, reports significant improvement in 50% of his severely ill patients.

Unfortunately, since 1996 little progress has been made in obtaining FDA approval of the drug. A seemingly endless series of lawsuits, missed deadlines and administrative setbacks effectively quashed the widespread support the drug had enjoyed in the 90s. In 2009, after the completion of Phase III of Ampligen’s drug trials, the FDA refused to grant Ampligen “new drug,” status which, in effect, relegated Ampligen once more to clinical trials. Hemispherx Biopharma again filed for approval of the drug to the FDA.

On December 20, 2012 a committee of advisers to the U.S. Food and Drug Administration (FDA) voted 9-4 against approving the drug. The committee determined that the drug had not been shown to be effective or safe. The committee’s decision was undoubtedly taken into consideration on February 4, 2013 when the FDA formally announced that it would not approve Ampligen. The FDA recommended that Hemispherx conduct at least one additional clinical trial, complete various nonclinical studies and perform a number of data analyses.

The FDA’s continued refusal to approve the drug in the U.S. has sparked Hemispherx Biopharma to market it in Latin America. On July 18, 2012 Hemispherx announced that it had filed for regulatory approval of Ampligen to treat Chronic Fatigue Syndrome & Myalgic Encephalomyelitis in Argentina. And on March 10, 2014 it announced that it and its partner in Latin America, GP Pharm, were planning on making applications in Chile, Peru and Uruguay for regulatory approval of Ampligen.



Rituximab (trade names: Rituxan, MabThera) is an antibody which acts against the protein CD20, a receptor found on the surface of B cells. Rituximab was first approved by the FDA in 1997 for the treatment of non-Hodgkin’s lymphoma. It is believed that Rituximab destroys tumors by attaching to the CD20 receptor on B cells, causing the tumor cells to disintegrate. In some non-Hodgkin’s B-cell lymphomas, Rituximab prevents the production of more tumor cells.

Rituximab is also used in the treatment of autoimmune disorders, such as rheumatoid arthritis and Wegener’s granulomatosis. In these cases, Rituximab works by temporarily depleting the total number of B cells, which are important in promoting inflammation. By depleting B cells, Rituximab reduces inflammation.

The effect of Rituximab on Chronic Fatigue Syndrome & Myalgic Encephalomyelitis patients was discovered by accident. Two Norwegian doctors, Øystein Fluge and Olav Mella of Haukeland University Hospital, noticed that after treating a ME/CFS patient for Hodgkin’s lymphoma with Rituximab, she recovered from ME/CFS. This led the doctors to initiate a small study of Rituximab on ME/CFS patients.

Three ME/CFS patients were given Rituximab in an open-label trial (that is, the patients knew they were receiving the drug). All three patients experienced significant improvement; two of them responded within six weeks and the third had a delayed response, occurring six months after treatment. The positive effects lasted for between 16 and 44 weeks. After relapse, the patients were administered another dose of Rituximab, with the same positive results. The investigators hypothesized that B-cells of the immune system might play a significant role in ME/CFS, at least for a subset of patients, and that “CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function.”

The positive result of this, as well as a second open-label trial, led Drs. Fluge and Mella to conduct a larger study with a more rigorous design to test the effects of the drug. In 2009 they initiated a double-blind, placebo-controlled phase trial with 30 Chronic Fatigue Syndrome & Myalgic Encephalomyelitis patients. As in the earlier open-label studies, the responses to Rituximab were significant. Sustained overall improvements were noted in 67% of the patients (as opposed to 13% of the control group). Four of the Rituximab patients showed improvement past the study period. The authors concluded that the delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, “suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses.”

These studies have prompted further trials. Invest in ME, a UK charity, has raised £295,000 for a large Rituximab trial in England. A Norwegian study at Haukland University Hospital has recruited 152 participants.

* Erica Verrillo is ProHealth’s expert editor for the ME/CFS HealthWatch and Natural Wellness newsletters. She is the author of Chronic Fatigue Syndrome: A Treatment Guide, 2nd Edition, available as an electronic book on Amazon,Barnes & Noble, Kobo and Payhip (PDF file). Her website,CFSTreatmentGuide.com, provides practical resources for patients with ME/CFS. She also writes a blog, Onward Through the Fog, with up-to-date news and information about the illness, as well as the full text of CFS: A Treatment Guide, 1st Edition (available in translation).


Further Reading



NIH webpage on clinical trials. Shows current status of Ampligen trials

Informative thread on patients’ experiences with Ampligen

Hemispherx Biopharma’s page on Ampligen

The Twisted History of Ampligen


A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome


The UK Rituximab Trial for ME

ABC article on Rituximab study

“Norwegian research breakthrough can solve CFS mystery.” English translation of first Norwegian news article on Rituximab

“Will Rituximab be a viable treatment option for ME/CFS.” An analysis of the possible role of Rituximab as a treatment for ME/CFS


Clinical impact of B-cell depletion with the anti-CD20 antibody Rituximab in chronic fatigue syndrome: a preliminary case series

Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study

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