Ampligen

Rintatolimod (tradename Ampligen) is a mismatched, double-stranded RNA molecule with immunomodulatory and antiviral properties. The drug acts as a TLR3 agonist which stimulates the production of interferons and tumor necrosis factors. It is manufactured by Hemispherx Biopharma.

It has been shown to raise natural killer cell function.

Mechanism of action
The chemical formation of Ampligen begins with the known immunostimulant called Polyinosinic:polycytidylic acid (usually abbreviated Poly I:C). Poly I:C is a mismatched double-stranded RNA (dsRNA) with one strand being a polymer of inosinic acid and the other strand a polymer of cytidylic acid.

Poly I:C is structurally similar to the type of dsRNA present in some viruses. When introduced into the body it stimulants the immune system because the body thinks a virus is present.

Ampligen is formed when uridine (one of the five standard nucleosides which form the building blocks of RNA) is introduced into this Poly I:C strand, altering the strand to Poly I:C12U.

As a result, one strand of the dsRNA is a homopolymer, poly rI and annealed to this strand is a heteropolymer, polyC12U.

This alteration increases the compound's instability and shortens the half life to less than 40 minutes after IV administration. Plasma RNase (an enzyme naturally present in blood) degrades the Ampligen compound into separate ribonucleotides which are completely natural degradation products the body can easily handle, thus lessening its toxicity.

Ampligen is a TLR3 agonist. It stimulates the production of toll-like receptor 3 (TLR3), which is a naturally occurring protein. TLR3 recognizes the dsRNA present in some viruses, such as retroviruses, and stimulates a series of biochemical reactions that result is an increase in the production of interferon. Interferon, an important player in the body's immune system, protects against viral infections and activates immune cells, such as natural killer cells (NK cells).

Reference: Slides 22-25 of Hemispherx's presentation to the FDA in 2012 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM334430.pdf

Drug approval status


Ampligen has been passed through five different FDA review divisions since 1990. Hemispherx Biopharma, Inc, wrote in a presentation to the FDA on Dec 20, 2012: "Most products have [the] same review Division during their entire development. Guidance from five (5) different Divisions [has provided] diverged/conflicting advice on major points, such as: interpreting primary endpoints (method of analysis), its collection and analysis, and different thresholds for determining toxicity and safety. In contrast, Hemispherx has had the same medical monitor for more than 20 years (Dr. David Strayer)."

Notable studies

 * 2016, Efficacy of rintatolimod in the treatment of chronic fatigue syndrome/ myalgic encephalomyelitis (cfs/me)
 * 2015, Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop
 * 2012, A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome

Learn more

 * Wikipedia - Rintatolimod
 * 2016, Ampligen and CFS
 * 2016, Hemispherx Biopharma (HEB) Comments on Recent Meeting with NIH for ME/CFS Research Advancement (see also NIH Post-Infectious ME/CFS Study)
 * 2016, Ampligen Co-Inventor / Head of Hemispherx Biopharma Fired: Implications for ME/CFS Drug Unclear
 * 2015, FDA Response Letter Regarding Approval of Ampligen for ME/CFS
 * 2015, Ampligen price more than doubles - Available soon in Europe
 * 2015, FDA Approval of MS Drug Puts Ampligen Back In Play
 * 2013, Ampligen and biomarkers: my testimony to FDA Dec 2012
 * 2012, Ampligen I: Effectiveness
 * 2012, Slide presentation to FDA Arthritis Advisory Committee by Hemispherx
 * 1994, The Aids Drug No One Can Have Mindy Kitei (see also Mindy Kitei)
 * 1990, Chronic Fatigue Syndrome